Comparative Benefits and Harms of Second-Generation Antidepressants: Background Paper for the American College of Physicians

Gerald Gartlehner; Bradley N. Gaynes; Richard A. Hansen; Patricia Thieda; Angela DeVeaugh-Geiss; Erin E. Krebs; Charity G. Moore; Laura Morgan; Kathleen N. Lohr

doi:10.7326/0003-4819-149-10-200811180-00008

Clinical Guidelines |18 November 2008

Comparative Benefits and Harms of Second-Generation Antidepressants: Background Paper for the American College of Physicians Free

Gerald Gartlehner, MD, MPH; Bradley N. Gaynes, MD, MPH; Richard A. Hansen, PhD, RPh; Patricia Thieda, MA; Angela DeVeaugh-Geiss, MS; Erin E. Krebs, MD, MPH; Charity G. Moore, PhD, MSPH; Laura Morgan, MA; Kathleen N. Lohr, PhD

Gerald Gartlehner, MD, MPH

From Danube University, Krems, Austria; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, and Regenstrief Institute, Indianapolis, Indiana; University of Pittsburgh, Pittsburgh, Pennsylvania; and RTI International, Research Triangle Park, North Carolina.

Bradley N. Gaynes, MD, MPH

Richard A. Hansen, PhD, RPh

Patricia Thieda, MA

Angela DeVeaugh-Geiss, MS

Erin E. Krebs, MD, MPH

Charity G. Moore, PhD, MSPH

Laura Morgan, MA

Kathleen N. Lohr, PhD

Article, Author, and Disclosure Information

From Danube University, Krems, Austria; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, and Regenstrief Institute, Indianapolis, Indiana; University of Pittsburgh, Pittsburgh, Pennsylvania; and RTI International, Research Triangle Park, North Carolina.
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.
Acknowledgment: The authors thank Timothy S. Carey, MD, MPH, and Stacey Williams, MA, from the University of North Carolina at Chapel Hill, and also Linda Lux, MPA, and Loraine Monroe of RTI International.
Grant Support: By a contract from the Agency for Healthcare Research and Quality to the RTI InternationalUniversity of North Carolina Evidence-based Practice Center (contract no. 290-02-0016).
Potential Financial Conflicts of Interest:Employment: A. DeVeaugh-Geiss (GlaxoSmithKline). Consultancies: B.N. Gaynes (Pfizer, Wyeth-Ayerst, Shire Pharmaceutical). Honoraria: B.N. Gaynes (GlaxoSmithKline). Stock ownership or options (other than mutual funds): A. DeVeaugh-Geiss (GlaxoSmithKline). Expert testimony: B.N. Gaynes (Phillips Lytle). Grants received: B.N. Gaynes (Agency for Healthcare Research and Quality, National Institute of Mental Health, Bristol-Myers Squibb, Novartis, Pfizer, Robert Wood Johnson Foundation, M-3 Corporation), R.A. Hansen (GlaxoSmithKline). Grants pending: B.N. Gaynes (National Institute of Mental Health, Agency for Healthcare Research and Quality).
Requests for Single Reprints: Gerald Gartlehner, MD, MPH, Danube University, Karl Dorrek-Strae, 3500 Krems, Austria; e-mail, gerald.gartlehner@donau-uni.ac.at.
Current Author Addresses: Dr. Gartlehner: Danube University, Karl Dorrek-Strae, 3500 Krems, Austria.
Dr. Gaynes: Department of Psychiatry, Campus Box 7160, University of North Carolina, Chapel Hill, NC 27599.
Dr. Hansen: University of North Carolina, School of Pharmacy, Campus Box 7360, Chapel Hill, NC 27599.
Ms. Thieda and Ms. Morgan: University of North Carolina, Sheps Center for Health Services Research, 725 Martin Luther King Jr. Boulevard, Chapel Hill, NC 27599.
Ms. DeVeaugh-Geiss: University of North Carolina, Department of Epidemiology, Campus Box 7435, Chapel Hill, NC 27599.
Dr. Krebs: Roudebush Veterans Affairs Medical Center, 1481 West 10th Street, Indianapolis, IN 46202.
Dr. Moore: Center for Research on Health Care Data, University of Pittsburgh, 200 Meyran Avenue, Suite 300, Pittsburgh, PA 15213.
Dr. Lohr: RTI International, PO Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194.

Abstract

Background:

Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing.

Purpose:

To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults.

Data Sources:

MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research.

Study Selection:

Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included.

Data Extraction:

Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes.

Data Synthesis:

If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression.

Limitation:

Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy.

Conclusion:

Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.

Major depressive disorder (MDD) is the most prevalent axis I disorder, affecting more than 16% of U.S. adults during their lifetime (1). In 2000, the economic burden of depressive disorders was an estimated $83.1 billion (2), more than 30% of which was attributable to direct medical expenses.

Pharmacotherapy dominates the medical management of MDD. Since the mid-1980s, second-generation antidepressants have gradually replaced tricyclic antidepressants and monoamine oxidase inhibitors as first-line medications, primarily because of their lower toxicity in overdose and similar general efficacy (3). These newer treatments include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, and other second-generation drugs (Table 1).

Table 1. Second-Generation Antidepressants Approved for Use in the United States

To date, only 2 systematic reviews have assessed the comparative efficacy and harms of second-generation antidepressants (3, 4). These studies reported no substantial differences in efficacy or harms among agents. However, because of a lack of direct head-to-head comparisons, assessments in both studies were primarily qualitative. Consequently, uncertainties persist about the differences among the drugs for which sufficient head-to-head evidence is lacking.

We systematically assessed evidence on the comparative benefits and harms of second-generation antidepressants for the acute, continuation, and maintenance phases of treatment of MDD; subsyndromal depression; and dysthymia and the comparative efficacy and effectiveness for such accompanying symptoms as anxiety, insomnia, or neurovegetative symptoms. We also sought to determine whether efficacy, effectiveness, and harms differed among subgroups of patients on the basis of age, sex, race or ethnicity, or comorbid conditions.

To our knowledge, this is the first meta-analysis of second-generation antidepressants to assess quantitatively all possible comparisons among drugs in this class. We update findings of an earlier report on these pharmaceuticals (5) for the Agency for Healthcare Research and Quality.

Methods

An open process (described at www.effectivehealthcare.ahrq.gov) involving the public, the Agency for Healthcare Research and Quality's Scientific Resource Center for Effective Health Care program, and various stakeholder groups produced key questions. We followed a standardized protocol for all review steps (5).

Data Sources

We searched MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007. We used Medical Subject Heading terms when available and keywords when appropriate. We combined terms for depressive disorders with a list of 12 specific second-generation antidepressantsbupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxineand their specific trade names. We limited electronic searches to adult 19 + years, human, and English language.

We manually searched reference lists of pertinent review articles and letters to the editor and used the Center for Drug Evaluation and Research database (up to April 2007) to identify unpublished research submitted to the U.S. Food and Drug Administration. The Scientific Resource Center invited pharmaceutical manufacturers to submit dossiers on completed research for each drug. We received dossiers from 3 pharmaceutical companies (Eli Lilly and Company, Indianapolis, Indiana; GlaxoSmithKline, Philadelphia, Pennsylvania; and Wyeth, Madison, New Jersey).

Study Selection

Two persons independently reviewed abstracts and relevant full-text articles. To assess efficacy or effectiveness regarding response, speed of onset, remission, maintenance of remission, and quality of life, we included head-to-head controlled trials of at least 6 weeks' duration that compared 1 drug with another. Because head-to-head evidence was lacking for many comparisons, we included placebo-controlled trials for indirect comparison models. To assess harms (specific adverse events, rates of adverse events, and discontinuations attributable to adverse events), we also examined data from observational studies with at least 100 participants and follow-up of at least 12 weeks. To assess differences of benefits and harms in subgroups and patients with accompanying symptoms, we reviewed both head-to-head and placebo-controlled trials. We included meta-analyses if we found them to be relevant for a key question and of good or fair methodological quality (6).

If both reviewers agreed that a study did not meet eligibility criteria, we excluded it. We also excluded studies that met eligibility criteria but were reported only as an abstract. Investigators resolved disagreements about inclusion or exclusion by consensus or by involving a third reviewer.

Data Extraction and Quality Assessment

We used a structured, Web-based data abstraction form (SRS 4.0, TrialStat, Ottawa, Ontario, Canada) onto which trained reviewers abstracted data from each study and assigned an initial quality rating. A senior reviewer read each abstracted article, evaluated completeness of data abstraction, and confirmed the quality rating. Investigators resolved disagreements by discussion and consensus or by consulting an independent party.

We assessed the internal validity (quality) of trials on the basis of predefined criteria and applied ratings of good, fair, or poor (5, 7, 8). Primary elements of quality assessment included randomization and allocation concealment, similarity of compared groups at baseline, blinding, use of intention-to-treat analysis, and overall and differential loss to follow-up. To assess observational studies, we used criteria involving selection of case patients or cohorts and control participants, adjustment for confounders, methods of outcomes assessment, length of follow-up, and statistical analysis (9). We rated studies with a fatal flaw in 1 or more categories as poor quality (Appendix Table 1) and did not include them in our analyses for this review unless no other head-to-head evidence was available. To identify effectiveness studies, we used a tool that distinguishes efficacy trials from effectiveness studies on the basis of certain elements of study design (10). Such studies have greater generalizability of results than efficacy trials because they enroll less selected study populations, use treatment modalities that mimic clinical practice, and assess health outcomes along with adverse events.

Lacking clear definitions about the equivalence of dosages among second-generation antidepressants in the published literature, we developed a roster of low, medium, and high dosages for each drug based on the interquartile dosing range (5). We used this roster, which does not indicate dosing equivalence, to detect gross inequalities in dosing that could affect comparative efficacy and effectiveness.

Appendix Table 1. Characteristics of Studies with Poor Internal Validity

Data Synthesis

If data were sufficient, we conducted meta-analyses of head-to-head comparisons. Efficacy outcomes included the relative benefit of achieving response (more than 50% improvement from baseline), which reflects the ratio of benefits in one treatment group to benefits in another, and the weighted mean difference of changes on the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale.

For each meta-analysis, we conducted a test of heterogeneity (I² index) and applied both random- and fixed-effects models. We report the random-effects results because the results from both models were very similar in all meta-analyses. We assessed publication bias by using funnel plots and the Begg adjusted rank correlation test (11) based on the Kendall coefficient.

Because no head-to-head evidence was available for the majority of drug comparisons, we conducted adjusted indirect comparisons (5). We employed meta-regressions of placebo-controlled trials by using individual drugs as covariates. When the number of trials was insufficient for meta-regressions, we used modified network meta-analysis (12). Evidence suggests that indirect comparisons agree with head-to-head trials if component studies are similar and treatment effects are expected to be consistent in patients included in different trials (13), although these assumptions are usually not verifiable.

All statistical analyses used StatsDirect Statistical Software program, version 2.3.8 (StatsDirect, Sale, United Kingdom); Stata, version 9.1 (StataCorp, College Station, Texas); and SAS, version 9.1 (SAS Institute, Cary, North Carolina).

Rating the Strength of Evidence

We rated the strength of the available evidence for specific key questions and outcomes in a 3-part hierarchy (high, moderate, and low) (5) by using a modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach (14, 15) that incorporates 4 key elements: study design, study quality, consistency of results, and directness (availability of data on outcomes or populations of interest).

Role of Funding Source

The Agency for Healthcare Research and Quality participated in formulating the key questions and reviewed and commented on planned methods and data analysis. The Agency had no role in study selection, quality ratings, or interpretation and synthesis of the evidence, although staff reviewed interim and final evidence reports and distributed them for external peer review by outside experts.

Results

We identified 2318 citations from searches and reviews of reference lists (Figure 1). Of the 203 included studies (Appendix Tables 2 to 11), 140 (69.0%) were financially supported by pharmaceutical companies and 19 (9.3%) by governmental agencies or independent funds. For 44 (21.7%) studies, we could not determine the funding source.

Figure 1.

Study flow diagram.

The number of included articles differs from the number of included studies because some studies have multiple publications.

Appendix Table 2. Comparative Efficacy and Effectiveness Studies on Therapy for Major Depressive Disorder

Appendix Table 3. Comparative Efficacy and Effectiveness Studies on Therapy for Dysthymia

Appendix Table 4. Comparative Efficacy and Effectiveness Studies on Therapy for Subsyndromal Depressive Disorders

Appendix Table 5. Comparative Efficacy and Effectiveness Studies on Maintaining Remission and Preventing Relapse

Appendix Table 6. Comparative Efficacy and Effectiveness Studies on Therapy for Recurrent and Treatment-Resistant Depression

Appendix Table 7. Placebo-Controlled Studies of Relapse and Recurrence

Appendix Table 8. Comparative Efficacy and Effectiveness Studies of Treatment in Adults with Major Depressive Disorder and Accompanying Symptoms

Appendix Table 9. Studies of Comparative Risk for Harms in Adults with Major Depressive Disorder

Appendix Table 10. Comparative Efficacy and Effectiveness Studies in Subgroups

Appendix Table 11. Randomized, Placebo-Controlled Trials Included for Indirect Comparisons

Major Depressive Disorder

Overall, we found no substantial differences in comparative efficacy and effectiveness of second-generation antidepressants for treatment of MDD (Tables 2, 3, and 4 and Figures 2, 3, and 4). This finding pertains to the acute, continuation, and maintenance phases of treatment; to patients with accompanying symptom clusters; and to subgroups defined by age, race or ethnicity, sex, or comorbid conditions (we found only sparse evidence for subgroups). Nevertheless, second-generation antidepressants are not identical drugs. They differ somewhat with respect to onset of action and frequency of some adverse events. Generally, effectiveness studies with less stringent eligibility criteria provided results similar to those of efficacy trials, indicating good generalizability of our findings to primary care populations.

Table 2. Summary of Findings on General Effectiveness

Table 3. Summary of Findings on Adverse Events: Comparative Risk for Harms

Table 4. Summary of Findings on Effectiveness in Subgroups

Figure 2.

Relative benefit of response comparing selective serotonin reuptake inhibitors (SSRIs) with other SSRIs

All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

* Based on meta-analysis of head-to-head trials.

Based on indirect comparisons with meta-regression.

Figure 3.

Relative benefit of response comparing selective serotonin reuptake inhibitors (SSRIs) with selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and SSRIs with serotonin and norepinephrine reuptake inhibitors (SNRIs

All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

* Based on meta-analysis of head-to-head trials.

Based on indirect comparisons with meta-regression.

Figure 4.

Relative benefit of response comparing selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other second-generation antidepressants (ADs) with other second-generation ADs.

All estimates are based on network meta-analyses except for those marked with an asterisk.* Based on meta-analysis of head-to-head trials.

Comparative Efficacy for Acute-Phase Treatment of MDD

Eighty good- or fair-quality head-to-head, randomized, controlled trials (RCTs), comprising more than 17000 patients, compared efficacy or effectiveness for acute-phase MDD treatment. These studies provided direct evidence for 36 of 66 possible comparisons among these drugs. Only 5 trials directly compared any second-generation nonselective serotonin reuptake inhibitor with another; of these, only 1 comparison was evaluated in more than 1 trial.

For the 62 comparisons of 1 drug with another for which data were available, we conducted indirect evaluations of response rates, incorporating an additional 34 placebo-controlled trials of good or fair quality comprising 26349 patients (Appendix Table 11).

For almost all comparisons, no statistically significant differences in response rates were apparent (Figures 2, 3, and 4). For some indirect comparisons, however, the precision of estimates was low and confidence intervals encompassed differences that would be clinically significant.

Findings from some meta-analyses yielded statistically significant differences among treatments, but the modest effect sizes of the differences are probably not clinically significant (5). For example, the meta-analytic comparison of response rates to citalopram versus escitalopram (1620) yielded a statistically significant additional treatment effect for escitalopram (relative benefit favoring escitalopram, 1.14 [95% CI, 1.04 to 1.26]) (5). Pooled differences of points on the Montgomery-Asberg Depression Rating Scale presented a mean additional treatment effect (weighted mean difference) of a 1.13-point reduction (CI, 0.18 to 2.09) for escitalopram (5). A 1.13-point change on the Montgomery-Asberg Depression Rating Scale represents about one fifth to one quarter of a standard deviation, so the clinical significance of this finding may be questionable. Methods research suggests that half a standard deviation constitutes a minimally important difference for health-related quality-of-life outcomes (21).

Meta-analyses yielded significantly lower response rates for fluoxetine than for sertraline (2225) or venlafaxine (2633). The small effect sizes of the differences are probably not clinically relevant.

Eighteen trials (18, 23, 3348), mostly of fair quality, included health-related quality of life or functional capacity as secondary outcome measures. We found no differences among second-generation antidepressants for these outcomes.

Comparative Effectiveness for Acute-Phase Treatment of MDD

Three studies (23, 49, 50) can be considered effectiveness rather than efficacy trials. Their findings were consistent with those of the efficacy trials. Two fair-quality effectiveness trials indicated that improvement of health-related quality of life (work, social and physical functioning, concentration and memory, and sexual functioning) was similar for fluoxetine, paroxetine, and sertraline (23, 50).

Speed of Response

Seven fair-quality studies (39, 40, 45, 5155) reported that mirtazapine had a significantly faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline after 1 or 2 weeks of treatment. All studies were supported by the manufacturer of mirtazapine. After 4 weeks of treatment, most response rates were similar. The extent to which the faster onset of mirtazapine can be extrapolated to other second-generation antidepressants is unclear. Mirtazapine and venlafaxine did not differ in speed of action (42).

Response to a Second Agent after Initial Treatment Failure

Overall, 38% of patients did not achieve a treatment response during 6 to 12 weeks of treatment with second-generation antidepressants; 54% did not achieve remission. The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial (56) provides the best evidence for assessing alternative medications among those for whom initial therapy failed. About 1 in 4 of the 727 people who participated in the switch of medications became symptom-free; this did not differ significantly among those who received sustained-release bupropion, sertraline, or extended-release venlafaxine. One open-label study (57) and a smaller efficacy study (58) reported significantly greater response rates for venlafaxine than for other second-generation drugs. Given the STAR*D findings, the clinical significance of this difference is questionable.

Maintaining Response or Remission after Treatment Success

Findings from 4 fair-quality head-to-head RCTs assessing relapse or recurrence prevention (5963) were similar for the comparisons of fluoxetine and sertraline, fluvoxamine and sertraline, duloxetine and paroxetine, and trazodone and venlafaxine. In 1 trial (59), among 105 patients who demonstrated a response at 8 weeks, 5 (10%) of 49 sertraline-treated patients and 7 (13%) of 56 of fluoxetine-treated patients had relapse over 24 weeks of continuation-phase treatment.

Efficacy or Effectiveness for Depression or Accompanying Symptoms

Clinicians may use symptom clusters that accompany depression (such as anxiety or insomnia) to guide antidepressant selection. This might improve outcomes for the depressive episode, the symptom cluster, or both. We reviewed available evidence for clinically relevant symptom clusters to address each possibility.

Treatment of Depression in Patients with Accompanying Symptom Clusters

Anxiety

Six fair-quality head-to-head trials (31, 35, 6468) suggest that antidepressants have similar antidepressive efficacy for patients with MDD and anxiety symptoms. These studies compared either fluoxetine or paroxetine with sertraline (259 patients with accompanying anxiety) (64, 65); sertraline with bupropion (972 patients; number with anxiety not provided) (6668); and sertraline with venlafaxine (20 patients with anxiety) (35). One fair-quality, 12-week trial (31) of 146 patients reported significantly greater response (75.0% vs. 49.3%) and remission rates (59.4% vs. 40.3%) with venlafaxine than with fluoxetine.

Insomnia

Two fair-quality head-to-head trials (441 patients with insomnia) (24, 69) provide limited evidence for similar efficacy of fluoxetine, nefazodone, paroxetine, or sertraline for treating depression in patients with accompanying insomnia. A pooled analysis of 3 RCTs (447 patients) (70) reported that the reduction on the Montgomery-Asberg Depression Rating Scale total score was significantly greater for patients receiving escitalopram than for those receiving citalopram (16.5 vs. 14.0); however, the clinical significance of this difference remains uncertain.

Melancholia

Two fair-quality head-to-head trials (286 patients) (28, 65) and 1 poor-quality head-to-head trial (68 patients) (71) assessed the effects of medications for treating depression in patients with melancholia. Although 2 studies reported greater response rates for sertraline than for fluoxetine (59% vs. 44%) (65) and for venlafaxine than for fluoxetine (70% vs. 50%) (71), the small sample sizes (87 and 68 patients) and high attrition rate (71) limit confidence in these findings.

Pain

We found no head-to-head evidence. Two placebo-controlled trials reported similar response rates for patients with MDD and pain who received duloxetine (72) or paroxetine (73) compared with those who received placebo.

Psychomotor Changes

The evidence is limited to subgroup analyses from 1 fair-quality head-to-head trial (65). Fluoxetine and sertraline had similar antidepressive efficacy among 47 patients with psychomotor retardation, but sertraline had higher efficacy among 78 patients with psychomotor agitation (65). Results should be interpreted cautiously because small sample sizes and multiple testing can lead to erroneous results in such subgroup analyses.

Treatment of Symptom Clusters in Patients with Accompanying Depression

Anxiety

Ten fair-quality head-to-head trials (31, 35, 40, 64, 66, 68, 7477) provide evidence that antidepressant medications do not differ substantially in efficacy for treatment of anxiety associated with MDD. Improvement of anxiety did not differ substantially among fluoxetine, paroxetine, and sertraline (549 patients) (64, 7577); sertraline and bupropion (243 patients) (66, 68); sertraline and venlafaxine (120 patients) (35); citalopram and mirtazapine (270 patients) (40); or paroxetine and nefazodone (206 patients) (74). One trial (146 patients) (31) reported significantly greater reductions in Covi Anxiety Scale scores of patients receiving venlafaxine than those receiving fluoxetine (5.7 vs. 3.9). The clinical significance of this difference remains uncertain.

Insomnia

Five fair-quality head-to-head trials (24, 37, 45, 62, 69) and a pooled analysis of 3 RCTs (70) involving 1540 patients provide limited evidence about the comparative effects of antidepressants on insomnia in patients with depression. Individual trials favored escitalopram over citalopram (70), nefazodone over fluoxetine (69), and trazodone over fluoxetine (37) and venlafaxine (62) in improving sleep scores. The comparisons were limited to single studies, and it is difficult to assess the clinical significance of these findings.

Pain

Three fair-quality head-to-head trials (63, 78, 79) and 1 poor-quality trial (80) compared duloxetine with paroxetine. These trials (1466 patients) found no substantial difference in pain relief between duloxetine and paroxetine.

Somatization

A fair-quality, 9-month open-label effectiveness trial reported similar improvement of somatization among 573 patients receiving fluoxetine, paroxetine, or sertraline (50).

Risk for Harms

We analyzed adverse events data from 80 head-to-head efficacy studies and 42 additional studies of both experimental and observational designs. Methods of adverse events assessment in efficacy trials differed greatly. Few studies used objective scales. Determining whether assessment methods were unbiased and adequate was often difficult.

Adverse Events Profiles

Constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and somnolence were commonly and consistently reported adverse events. On average, 61% of patients in efficacy trials experienced at least 1 adverse event. Nausea and vomiting were the most common reasons for discontinuation in efficacy studies.

Overall, second-generation antidepressants had similar adverse events profiles. Table 5 summarizes some differences in the incidence of specific adverse events.

Table 5. Main Differences in Specific Adverse Events

Sexual Dysfunction

A fair-quality prospective observational study (1022 patients) from Spain reported that 59% of patients treated with second-generation antidepressants experienced sexual dysfunction (81). On the basis of 5 RCTs (1489 patients), bupropion led to a significantly lower rate of sexual adverse events than fluoxetine and sertraline (8286). Paroxetine frequently led to higher rates of sexual dysfunction than did fluoxetine, fluvoxamine, nefazodone, or sertraline (16% vs. 6%) (24, 76, 87, 88). Underreporting of absolute rates of sexual dysfunction is likely in these studies.

Suicidality

Eleven studies (8999) assessed the risk for suicidality (suicidal thinking or behavior) in patients treated with second-generation antidepressants; comparative data are sparse. No particular drug has an excess risk compared with any other drug in this class (94, 98). These findings are based primarily on retrospective cohort studies (91, 93, 94, 98). Confounding by indication (patients at higher risk for suicide being prescribed certain medications rather than others) may have led to erroneous conclusions.

The United Kingdom's Committee on Safety of Medicines conducted the largest attempt to determine whether second-generation antidepressants increase the risk for suicidality in 2004 (89). A good meta-analysis of placebo-controlled trials of selective serotonin reuptake inhibitors, comprising more than 40000 adults, yielded no evidence that these agents increase the risk for suicide (odds ratio, 0.85 [CI, 0.20 to 3.40]) but did reveal an increased risk for nonfatal suicide attempts (odds ratio, 1.57 [CI, 0.99 to 2.55]) (92).

Another good meta-analysis of published trial data (90), comprising more than 87000 patients, reported a significantly higher risk for suicide attempts among patients receiving selective serotonin reuptake inhibitors than among those receiving placebo (odds ratio, 2.25 [CI, 1.14 to 4.55]). This study estimated the overall rate of suicide attempts as 3.9 (CI, 3.3 to 4.6) per 1000 patients treated with these drugs, with an incidence of 18.2 suicide attempts per 1000 patient-years.

Other Severe Adverse Events

Evidence on the comparative risk for rare but severe adverse events, such as seizures, cardiovascular events (events relating to systolic and diastolic blood pressure and pulse or heart rate), hyponatremia, hepatotoxicity, and the serotonin syndrome, is insufficient to draw firm conclusions. Clinicians should keep in mind the risk for such harms when treating patients with a second-generation antidepressant.

Treatment of MDD in Subgroups

No study directly compared efficacy, effectiveness, and harms of second-generation antidepressants between subgroups and the general population for treatment of depression syndromes. Numerous studies, however, conducted subgroup analyses or used subgroups as the study population.

Age

Multiple head-to-head trials (22, 44, 48, 50, 54, 100107) and 2 fair-quality meta-analyses (108, 109) indicated that the efficacy of second-generation antidepressants does not differ in elderly patients (65 to 80 years of age) or very elderly patients (##gt##80 years of age) compared with younger patients. These findings are consistent with placebo-controlled trials (110116) conducted in elderly or very elderly patients, which reported effect sizes similar to those from trials in younger patients.

Sex

Efficacy trials did not show differences between men and women (108, 109, 117). Observational evidence supports this conclusion (118).

Race or Ethnicity

One trial that evaluated efficacy differences in racial subgroups (119) did not show any differences, but this trial was rated poor quality because it lacked an intention-to-treat analysis.

Comorbid Conditions

No study directly compared efficacy, effectiveness, and harms of second-generation antidepressants between depressed patients with comorbid conditions and the general population.

One poor-quality head-to-head study did not detect differences in efficacy and tolerability among fluoxetine, paroxetine, or sertraline in depressed individuals with HIV or AIDS (120).

Seventeen placebo-controlled trials of varying quality (119, 121136) and 1 fair-quality systematic review (137) evaluated second-generation antidepressants in patients with various comorbid conditions. Some studies suggested that these drugs may not be efficacious for depressed patients with such comorbid conditions as HIV or AIDS (119, 121, 122), alcohol abuse (123125), Alzheimer disease (127), stroke (133, 134), or substance abuse (135, 136). Many of the studies were not powered to detect a meaningful difference between active treatment and placebo.

Dysthymia

Dysthymia is a chronic depressive disorder that is characterized by depressed mood for more days than not for at least 2 years (138). We found no head-to-head trial that studied patients with dysthymia. One good-quality trial (38) and 4 fair-quality placebo-controlled trials (36, 43, 139142) provide mixed evidence on the general efficacy and effectiveness of fluoxetine, paroxetine, and sertraline for the treatment of dysthymia.

Subsyndromal Depression

Subsyndromal depression (also called minor depression) is a mood disturbance of at least 2 weeks' duration with fewer symptoms of depression than MDD (138). One nonrandomized, open-label trial (100) compared citalopram with sertraline but found no difference in efficacy. Findings from 2 placebo-controlled trials (141143) were insufficient to draw any conclusions about comparative efficacy and effectiveness of second-generation antidepressants for the treatment of subsyndromal depression.

Discussion

In this systematic review of data from 203 studies, direct and indirect comparisons yielded no substantial differences in efficacy for the treatment of MDD. Statistically significant results were small and are unlikely to have clinical significance.

Existing evidence on efficacy does not warrant the choice of one second-generation antidepressant over another, although we could not conclusively establish equivalence in efficacy for many comparisons. No differences in efficacy were apparent for patients with accompanying symptoms or subgroups based on age, sex, race or ethnicity, or comorbid conditions, although evidence within subgroups was limited.

Nevertheless, second-generation antidepressants cannot be considered identical drugs. Moderate-strength evidence supports some differences among individual drugs with respect to speed of onset of response and incidence of some adverse events. For example, consistent evidence from multiple trials demonstrated that mirtazapine has a faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline (39, 45, 5255) and that bupropion has fewer sexual adverse events than fluoxetine, paroxetine, or sertraline (82, 86, 144). These differences may be clinically significant and may influence medication choice for a given patient.

Across all efficacy trials, more than 50% of patients treated with second-generation antidepressants for acute-phase depression did not achieve remission, the primary goal of depression treatment. Almost 40% did not achieve response, a less rigorous outcome. Current evidence is insufficient to identify patient factors that can reliably predict response or nonresponse to an individual drug. Although limited evidence indicates that the efficacy of second-generation antidepressants is similar among patients for whom treatment with a first-line agent failed, a substantial proportion of these patients do not achieve response or remission with second-line treatment (56). Multiple treatment options are required for patients who do not respond to first- or second-line treatment.

Our statistical comparisons confirm the results of previous systematic reviews (3, 4, 145), although our interpretation of findings differs from that of Cipriani and colleagues (145) in their recent meta-analysis comparing fluoxetine with other antidepressants. Their pooled estimates of response rates for fluoxetine compared with sertraline and venlafaxine were slightly larger than our results. These differences might be attributable to their inclusion of open-label trials or their use of odds ratios, which overestimate differences when event rates are high. As in our study, the effect size meta-analysis by Cipriani and colleagues did not reach statistical significance, but they interpreted these differences as clinically significant.

Our review has several limitations. First, most of the studies were efficacy trials conducted in highly selected populations. The applicability of their results to the average patient with acute MDD might be limited. However, the fact that the effectiveness trial results (23, 49, 50) were consistent with the efficacy study results strengthens our findings.

Indirect comparisons have methodological limitations, most notably a lack of power that resulted in wide confidence intervals, which can encompass clinically significant differences between treatments. Nevertheless, we believe that the consistent similarity of treatment effects across all comparisons supports our conclusion that no substantial differences exist.

Publication bias is a concern for all systematic reviews. Selective availability of studies with positive results can seriously bias conclusions, particularly when a pharmaceutical company compares 2 of its own drugs (as in the case of citalopram and escitalopram). Selective reporting is conceivable; however, we found no evidence to prove publication bias. The validity of statistical methods to explore publication bias, such as funnel plots, is limited because of the small number of studies for individual comparisons.

Although our review included more than 200 studies, many questions remain. More evidence is needed on the most appropriate duration of antidepressant treatment for maintaining response and remission. Future studies should evaluate whether different formulations (for example, controlled release vs. immediate release) lead to differences in adherence and subsequent relapse or recurrence. In addition, although most trials maintained the dose used in acute-phase treatment throughout the continuation and maintenance phases of treatment, little is known about how drug dose affects the risk for relapse or recurrence. Future research is also needed to reliably establish the general efficacy of second-generation antidepressants for the treatment of dysthymia and subsyndromal depression.

How do our findingsthat pharmacologic differences between second-generation antidepressants do not translate into substantial clinical differences, although tolerability may differinform the practicing clinician? Given the difficulty in predicting what medication will be both efficacious for and tolerated by an individual patient, familiarity with a broad spectrum of antidepressants is prudent. An emphasis on providing treatment trials of adequate dose and duration, with recent evidence providing support for maximum but tolerable doses for at least 8 weeks (146), seems at least as important as the choice of specific drug.

References

Kessler
RC
,
Berglund
P
,
Demler
O
,
Jin
R
,
Merikangas
KR
,
Walters
EE
.
Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.
Arch Gen Psychiatry
2005
62
593
602
PubMed
CrossRef

PubMed
Greenberg
PE
,
Kessler
RC
,
Birnbaum
HG
,
Leong
SA
,
Lowe
SW
,
Berglund
PA
.
The economic burden of depression in the United States: how did it change between 1990 and 2000?
J Clin Psychiatry
2003
64
1465
75
PubMed
CrossRef

PubMed
Williams
JW
Jr
,
Mulrow
CD
,
Chiquette
E
,
Nol
PH
,
Aguilar
C
,
Cornell
J
.
A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.
Ann Intern Med
2000
132
743
56
CrossRef

PubMed
Hansen
RA
,
Gartlehner
G
,
Lohr
KN
,
Gaynes
BN
,
Carey
TS
.
Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder.
Ann Intern Med
2005
143
415
26
CrossRef

PubMed
Gartlehner G, Hansen RA, Thieda P, DeVeaugh-Geiss AM, Gaynes BN, Krebs EE, et al. Comparative Effectiveness of Second-generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7-EHC007-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2007. Accessed at www.effectivehealthcare.ahrq.gov/reports/final.cfm on 30 September 2008.
Balk
EM
,
Lau
J
,
Bonis
PA
.
Reading and critically appraising systematic reviews and meta-analyses: a short primer with a focus on hepatology.
J Hepatol
2005
43
729
36
PubMed
CrossRef

PubMed
Harris
RP
,
Helfand
M
,
Woolf
SH
,
Lohr
KN
,
Mulrow
CD
,
Teutsch
SM
.
Methods Work Group
Third US Preventive Services Task Force
Current methods of the US Preventive Services Task Force: a review of the process.
Am J Prev Med
2001
20
21
35
PubMed
CrossRef

PubMed
Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews. CRD Report Number 4. 2nd ed. York, United Kingdom: Univ of York; 2001. Accessed at www.york.ac.uk/inst/crd/report4.htm on 3 October 2008.
Deeks
JJ
,
Dinnes
J
,
D'Amico
R
,
Sowden
AJ
,
Sakarovitch
C
,
Song
F
.
International Stroke Trial Collaborative Group
Evaluating non-randomised intervention studies.
Health Technol Assess
2003
7
iii
x, 1-173
PubMed
CrossRef

PubMed
Gartlehner
G
,
Hansen
RA
,
Nissman
D
,
Lohr
KN
,
Carey
TS
.
A simple and valid tool distinguished efficacy from effectiveness studies.
J Clin Epidemiol
2006
59
1040
8
PubMed
CrossRef

PubMed
Begg
CB
,
Mazumdar
M
.
Operating characteristics of a rank correlation test for publication bias.
Biometrics
1994
50
1088
101
PubMed
CrossRef

PubMed
Lumley
T
.
Network meta-analysis for indirect treatment comparisons.
Stat Med
2002
21
2313
24
PubMed
CrossRef

PubMed
Glenny
AM
,
Altman
DG
,
Song
F
,
Sakarovitch
C
,
Deeks
JJ
,
D'Amico
R
.
International Stroke Trial Collaborative Group
Indirect comparisons of competing interventions.
Health Technol Assess
2005
9
1
134, iii-iv
PubMed
CrossRef

PubMed
Atkins
D
,
Eccles
M
,
Flottorp
S
,
Guyatt
GH
,
Henry
D
,
Hill
S
.
GRADE Working Group
Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group.
BMC Health Serv Res
2004
4
38
PubMed
CrossRef

PubMed
Guyatt
G
,
Gutterman
D
,
Baumann
MH
,
Addrizzo-Harris
D
,
Hylek
EM
,
Phillips
B
.
Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force.
Chest
2006
129
174
81
PubMed
CrossRef

PubMed
Lepola
UM
,
Loft
H
,
Reines
EH
.
Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care.
Int Clin Psychopharmacol
2003
18
211
7
PubMed
CrossRef

PubMed
Colonna
L
,
Andersen
HF
,
Reines
EH
.
A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder.
Curr Med Res Opin
2005
21
1659
68
PubMed
CrossRef

PubMed
Burke
WJ
,
Gergel
I
,
Bose
A
.
Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients.
J Clin Psychiatry
2002
63
331
6
PubMed
CrossRef

PubMed
Moore
N
,
Verdoux
H
,
Fantino
B
.
Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.
Int Clin Psychopharmacol
2005
20
131
7
PubMed
CrossRef

PubMed
FDA Center for Drug Evaluation and Research. Statistical Review of NDA 21-323 (Escitalopram Oxalate). Rockville, MD: U.S. Food and Drug Administration; 2001. Accessed at www.fda.gov/cder/foi/nda/2002/21-323.pdf_Lexapro_Statr.pdf on 3 October 2008.
Norman
GR
,
Sloan
JA
,
Wyrwich
KW
.
Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation.
Med Care
2003
41
582
92
PubMed
PubMed
Newhouse
PA
,
Krishnan
KR
,
Doraiswamy
PM
,
Richter
EM
,
Batzar
ED
,
Clary
CM
.
A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients.
J Clin Psychiatry
2000
61
559
68
PubMed
CrossRef

PubMed
Sechter
D
,
Troy
S
,
Paternetti
S
,
Boyer
P
.
A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients.
Eur Psychiatry
1999
14
41
8
PubMed
CrossRef

PubMed
Fava
M
,
Hoog
SL
,
Judge
RA
,
Kopp
JB
,
Nilsson
ME
,
Gonzales
JS
.
Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia.
J Clin Psychopharmacol
2002
22
137
47
PubMed
CrossRef

PubMed
Bennie
EH
,
Mullin
JM
,
Martindale
JJ
.
A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression.
J Clin Psychiatry
1995
56
229
37
PubMed
PubMed
Costa e Silva
J
.
Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression.
J Clin Psychiatry
1998
59
352
7
PubMed
CrossRef

PubMed
Alves
C
,
Cachola
I
,
Brandao
J
.
Efficacy and tolerability of venlafaxine and fluoxetine in outpatients with major depression.
Primary Care Psychiatry
1999
5
57
63
Tzanakaki
M
,
Guazzelli
M
,
Nimatoudis
I
,
Zissis
NP
,
Smeraldi
E
,
Rizzo
F
.
Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia.
Int Clin Psychopharmacol
2000
15
29
34
PubMed
CrossRef

PubMed
Tylee
A
,
Beaumont
G
,
Bowden
MW
,
Reynolds
A
.
A double-blind, randomized, 12-week comparison study of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general practice.
Primary Care Psychiatry
1997
3
51
8
Rudolph
RL
,
Feiger
AD
.
A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression.
J Affect Disord
1999
56
171
81
PubMed
CrossRef

PubMed
De Nayer
A
,
Geerts
S
,
Ruelens
L
,
Schittecatte
M
,
De Bleeker
E
,
Van Eeckhoutte
I
.
Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety.
Int J Neuropsychopharmacol
2002
5
115
20
PubMed
CrossRef

PubMed
Dierick
M
,
Ravizza
L
,
Realini
R
,
Martin
A
.
A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients.
Prog Neuropsychopharmacol Biol Psychiatry
1996
20
57
71
PubMed
CrossRef

PubMed
Nemeroff
CB
,
Thase
ME
.
EPIC 014 Study Group
A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients.
J Psychiatr Res
2007
41
351
9
PubMed
CrossRef

PubMed
Aberg-Wistedt
A
,
Agren
H
,
Ekselius
L
,
Bengtsson
F
,
Akerblad
AC
.
Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy.
J Clin Psychopharmacol
2000
20
645
52
PubMed
CrossRef

PubMed
Sir
A
,
D'Souza
RF
,
Uguz
S
,
George
T
,
Vahip
S
,
Hopwood
M
.
Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms.
J Clin Psychiatry
2005
66
1312
20
PubMed
CrossRef

PubMed
Ravindran
AV
,
Guelfi
JD
,
Lane
RM
,
Cassano
GB
.
Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression.
J Clin Psychiatry
2000
61
821
7
PubMed
CrossRef

PubMed
Beasley
CM
Jr
,
Dornseif
BE
,
Pultz
JA
,
Bosomworth
JC
,
Sayler
ME
.
Fluoxetine versus trazodone: efficacy and activating-sedating effects.
J Clin Psychiatry
1991
52
294
9
PubMed
PubMed
Devanand
DP
,
Nobler
MS
,
Cheng
J
,
Turret
N
,
Pelton
GH
,
Roose
SP
.
Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.
Am J Geriatr Psychiatry
2005
13
59
68
PubMed
CrossRef

PubMed
Wheatley
DP
,
van Moffaert
M
,
Timmerman
L
,
Kremer
CM
.
Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.
J Clin Psychiatry
1998
59
306
12
PubMed
CrossRef

PubMed
Leinonen
E
,
Skarstein
J
,
Behnke
K
,
Agren
H
,
Helsdingen
JT
.
Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group.
Int Clin Psychopharmacol
1999
14
329
37
PubMed
CrossRef

PubMed
McPartlin
GM
,
Reynolds
A
,
Anderson
C
,
Casoy
J
.
A comparison of once-daily venlafaxine XR and paroxetine in depressed outpatients treated in general practice.
Primary Care Psychiatry
1998
127
32
Guelfi
JD
,
Ansseau
M
,
Timmerman
L
,
Krsgaard
S
.
Mirtazapine-Venlafaxine Study Group
Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.
J Clin Psychopharmacol
2001
21
425
31
PubMed
CrossRef

PubMed
Vanelle
JM
,
Attar-Levy
D
,
Poirier
MF
,
Bouhassira
M
,
Blin
P
,
Oli
JP
.
Controlled efficacy study of fluoxetine in dysthymia.
Br J Psychiatry
1997
170
345
50
PubMed
CrossRef

PubMed
Weihs
KL
,
Settle
EC
Jr
,
Batey
SR
,
Houser
TL
,
Donahue
RM
,
Ascher
JA
.
Bupropion sustained release versus paroxetine for the treatment of depression in the elderly.
J Clin Psychiatry
2000
61
196
202
PubMed
CrossRef

PubMed
Versiani
M
,
Moreno
R
,
Ramakers-van Moorsel
CJ
,
Schutte
AJ
.
Comparative Efficacy Antidepressants Study Group
Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients.
CNS Drugs
2005
19
137
46
PubMed
CrossRef

PubMed
Boyer
P
,
Danion
JM
,
Bisserbe
JC
,
Hotton
JM
,
Troy
S
.
Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France.
Pharmacoeconomics
1998
13
157
69
PubMed
CrossRef

PubMed
Bielski
RJ
,
Ventura
D
,
Chang
CC
.
A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder.
J Clin Psychiatry
2004
65
1190
6
PubMed
CrossRef

PubMed
Finkel
SI
,
Richter
EM
,
Clary
CM
,
Batzar
E
.
Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression.
Am J Geriatr Psychiatry
1999
7
221
7
PubMed
CrossRef

PubMed
Ekselius
L
,
von Knorring
L
,
Eberhard
G
.
A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.
Int Clin Psychopharmacol
1997
12
323
31
PubMed
CrossRef

PubMed
Kroenke
K
,
West
SL
,
Swindle
R
,
Gilsenan
A
,
Eckert
GJ
,
Dolor
R
.
Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial.
JAMA
2001
286
2947
55
PubMed
CrossRef

PubMed
Hong
CJ
,
Hu
WH
,
Chen
CC
,
Hsiao
CC
,
Tsai
SJ
,
Ruwe
FJ
.
A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients.
J Clin Psychiatry
2003
64
921
6
PubMed
CrossRef

PubMed
Benkert
O
,
Szegedi
A
,
Kohnen
R
.
Mirtazapine compared with paroxetine in major depression.
J Clin Psychiatry
2000
61
656
63
PubMed
CrossRef

PubMed
Szegedi
A
,
Mller
MJ
,
Anghelescu
I
,
Klawe
C
,
Kohnen
R
,
Benkert
O
.
Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression.
J Clin Psychiatry
2003
64
413
20
PubMed
CrossRef

PubMed
Schatzberg
AF
,
Kremer
C
,
Rodrigues
HE
,
Murphy
GM
Jr
.
Mirtazapine vs. Paroxetine Study Group
Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.
Am J Geriatr Psychiatry
2002
10
541
50
PubMed
CrossRef

PubMed
Behnke
K
,
Sgaard
J
,
Martin
S
,
Buml
J
,
Ravindran
AV
,
Agren
H
.
Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.
J Clin Psychopharmacol
2003
23
358
64
PubMed
CrossRef

PubMed
Rush
AJ
,
Trivedi
MH
,
Wisniewski
SR
,
Stewart
JW
,
Nierenberg
AA
,
Thase
ME
.
STAR*D Study Team
Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.
N Engl J Med
2006
354
1231
42
PubMed
CrossRef

PubMed
Baldomero
EB
,
Ubago
JG
,
Cercs
CL
,
Ruiloba
JV
,
Calvo
CG
,
Lpez
RP
.
Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study.
Depress Anxiety
2005
22
68
76
PubMed
CrossRef

PubMed
Poirier
MF
,
Boyer
P
.
Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison.
Br J Psychiatry
1999
175
12
6
PubMed
CrossRef

PubMed
van Moffaert
M
,
Bartholome
F
,
Cosyns
P
,
De Nayer
AR
.
A controlled comparison of sertraline and fluoxetine in acute and continuation treatment of major depression.
Hum Psychopharmacol
1995
10
393
405
CrossRef
Franchini
L
,
Gasperini
M
,
Perez
J
,
Smeraldi
E
,
Zanardi
R
.
A double-blind study of long-term treatment with sertraline or fluvoxamine for prevention of highly recurrent unipolar depression.
J Clin Psychiatry
1997
58
104
7
PubMed
CrossRef

PubMed
Franchini
L
,
Gasperini
M
,
Zanardi
R
,
Smeraldi
E
.
Four-year follow-up study of sertraline and fluvoxamine in long-term treatment of unipolar subjects with high recurrence rate.
J Affect Disord
2000
58
233
6
PubMed
CrossRef

PubMed
Cunningham
LA
,
Borison
RL
,
Carman
JS
,
Chouinard
G
,
Crowder
JE
,
Diamond
BI
.
A comparison of venlafaxine, trazodone, and placebo in major depression.
J Clin Psychopharmacol
1994
14
99
106
PubMed
CrossRef

PubMed
Perahia
DG
,
Wang
F
,
Mallinckrodt
CH
,
Walker
DJ
,
Detke
MJ
.
Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial.
Eur Psychiatry
2006
21
367
78
PubMed
CrossRef

PubMed
Fava
M
,
Rosenbaum
JF
,
Hoog
SL
,
Tepner
RG
,
Kopp
JB
,
Nilsson
ME
.
Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression.
J Affect Disord
2000
59
119
26
PubMed
CrossRef

PubMed
Flament
MF
,
Lane
RM
,
Zhu
R
,
Ying
Z
.
Predictors of an acute antidepressant response to fluoxetine and sertraline.
Int Clin Psychopharmacol
1999
14
259
75
PubMed
CrossRef

PubMed
Rush
AJ
,
Trivedi
MH
,
Carmody
TJ
,
Donahue
RM
,
Houser
TL
,
Bolden-Watson
C
.
Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline.
Neuropsychopharmacology
2001
25
131
8
PubMed
CrossRef

PubMed
Rush
AJ
,
Batey
SR
,
Donahue
RM
,
Ascher
JA
,
Carmody
TJ
,
Metz
A
.
Does pretreatment anxiety predict response to either bupropion SR or sertraline?
J Affect Disord
2001
64
81
7
PubMed
CrossRef

PubMed
Trivedi
MH
,
Rush
AJ
,
Carmody
TJ
,
Donahue
RM
,
Bolden-Watson
C
,
Houser
TL
.
Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients?
J Clin Psychiatry
2001
62
776
81
PubMed
CrossRef

PubMed
Rush
AJ
,
Armitage
R
,
Gillin
JC
,
Yonkers
KA
,
Winokur
A
,
Moldofsky
H
.
Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder.
Biol Psychiatry
1998
44
3
14
PubMed
CrossRef

PubMed
Lader
M
,
Andersen
HF
,
Baekdal
T
.
The effect of escitalopram on sleep problems in depressed patients.
Hum Psychopharmacol
2005
20
349
54
PubMed
CrossRef

PubMed
Clerc
GE
,
Ruimy
P
,
Verdeau-Palls
J
.
A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group.
Int Clin Psychopharmacol
1994
9
139
43
PubMed
CrossRef

PubMed
Brannan
SK
,
Mallinckrodt
CH
,
Brown
EB
,
Wohlreich
MM
,
Watkin
JG
,
Schatzberg
AF
.
Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder.
J Psychiatr Res
2005
39
43
53
PubMed
CrossRef

PubMed
Dickens
C
,
Jayson
M
,
Sutton
C
,
Creed
F
.
The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain.
Psychosomatics
2000
41
490
9
PubMed
CrossRef

PubMed
Baldwin
DS
,
Hawley
CJ
,
Abed
RT
,
Maragakis
BP
,
Cox
J
,
Buckingham
SA
.
A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression.
J Clin Psychiatry
1996
57
46
52
PubMed
PubMed
Chouinard
G
,
Saxena
B
,
Blanger
MC
,
Ravindran
A
,
Bakish
D
,
Beauclair
L
.
A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder.
J Affect Disord
1999
54
39
48
PubMed
CrossRef

PubMed
Fava
M
,
Amsterdam
JD
,
Deltito
JA
,
Salzman
C
,
Schwaller
M
,
Dunner
DL
.
A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression.
Ann Clin Psychiatry
1998
10
145
50
PubMed
CrossRef

PubMed
Gagiano
CA
.
A double blind comparison of paroxetine and fluoxetine in patients with major depression.
Br J Clin Res
1993
4
145
52
Detke
MJ
,
Wiltse
CG
,
Mallinckrodt
CH
,
McNamara
RK
,
Demitrack
MA
,
Bitter
I
.
Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial.
Eur Neuropsychopharmacol
2004
14
457
70
PubMed
CrossRef

PubMed
Clinical Study Summary: Study F1J-MC-HMAT Study Group A. Indianapolis, IN: Eli Lilly; 2004. Accessed at www.clinicalstudyresults.org/drugdetails/?unique_id=4091a##amp##sort=c.company_name##amp##page=1##amp##drug_id=170 on 30 September 2008.
Goldstein
DJ
,
Lu
Y
,
Detke
MJ
,
Wiltse
C
,
Mallinckrodt
C
,
Demitrack
MA
.
Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine.
J Clin Psychopharmacol
2004
24
389
99
PubMed
CrossRef

PubMed
Montejo
AL
,
Llorca
G
,
Izquierdo
JA
,
Rico-Villademoros
F
.
Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.
J Clin Psychiatry
2001
62
10
21
PubMed
PubMed
Coleman
CC
,
King
BR
,
Bolden-Watson
C
,
Book
MJ
,
Segraves
RT
,
Richard
N
.
A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine.
Clin Ther
2001
23
1040
58
PubMed
CrossRef

PubMed
Segraves
RT
,
Kavoussi
R
,
Hughes
AR
,
Batey
SR
,
Johnston
JA
,
Donahue
R
.
Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment.
J Clin Psychopharmacol
2000
20
122
8
PubMed
CrossRef

PubMed
Coleman
CC
,
Cunningham
LA
,
Foster
VJ
,
Batey
SR
,
Donahue
RM
,
Houser
TL
.
Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.
Ann Clin Psychiatry
1999
11
205
15
PubMed
CrossRef

PubMed
Croft
H
,
Settle
E
Jr
,
Houser
T
,
Batey
SR
,
Donahue
RM
,
Ascher
JA
.
A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline.
Clin Ther
1999
21
643
58
PubMed
CrossRef

PubMed
Feighner
JP
,
Gardner
EA
,
Johnston
JA
,
Batey
SR
,
Khayrallah
MA
,
Ascher
JA
.
Double-blind comparison of bupropion and fluoxetine in depressed outpatients.
J Clin Psychiatry
1991
52
329
35
PubMed
PubMed
Hicks
JA
,
Argyropoulos
SV
,
Rich
AS
,
Nash
JR
,
Bell
CJ
,
Edwards
C
.
Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression.
Br J Psychiatry
2002
180
528
35
PubMed
CrossRef

PubMed
Kiev
A
,
Feiger
A
.
A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients.
J Clin Psychiatry
1997
58
146
52
PubMed
CrossRef

PubMed
Committee on Safety of Medicines. Report of the CSM expert working group on the safety of selective serotonin reuptake inhibitor antidepressants. London: Medicines and Healthcare products Regulatory Agency; 2004. Accessed at www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con019472.pdf on 2 December 2008.
Fergusson
D
,
Doucette
S
,
Glass
KC
,
Shapiro
S
,
Healy
D
,
Hebert
P
.
Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials.
BMJ
2005
330
396
PubMed
CrossRef

PubMed
Martinez
C
,
Rietbrock
S
,
Wise
L
,
Ashby
D
,
Chick
J
,
Moseley
J
.
Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case##ndash##control study.
BMJ
2005
330
389
PubMed
CrossRef

PubMed
Gunnell
D
,
Saperia
J
,
Ashby
D
.
Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review.
BMJ
2005
330
385
PubMed
CrossRef

PubMed
Didham
RC
,
McConnell
DW
,
Blair
HJ
,
Reith
DM
.
Suicide and self-harm following prescription of SSRIs and other antidepressants: confounding by indication.
Br J Clin Pharmacol
2005
60
519
25
PubMed
CrossRef

PubMed
Jick
H
,
Kaye
JA
,
Jick
SS
.
Antidepressants and the risk of suicidal behaviors.
JAMA
2004
292
338
43
PubMed
CrossRef

PubMed
Jick
SS
,
Dean
AD
,
Jick
H
.
Antidepressants and suicide.
BMJ
1995
310
215
8
PubMed
CrossRef

PubMed
Jick
H
,
Ulcickas
M
,
Dean
A
.
Comparison of frequencies of suicidal tendencies among patients receiving fluoxetine, lofepramine, mianserin, or trazodone.
Pharmacotherapy
1992
12
451
4
PubMed
PubMed
Aursnes
I
,
Tvete
IF
,
Gaasemyr
J
,
Natvig
B
.
Suicide attempts in clinical trials with paroxetine randomised against placebo.
BMC Med
2005
3
14
PubMed
CrossRef

PubMed
Khan
A
,
Khan
S
,
Kolts
R
,
Brown
WA
.
Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports.
Am J Psychiatry
2003
160
790
2
PubMed
CrossRef

PubMed
Lopez-Iibor
.
Reduced suicidality with paroxetine.
Eur Psychiatry
1993
8
17S
19S
Rocca
P
,
Calvarese
P
,
Faggiano
F
,
Marchiaro
L
,
Mathis
F
,
Rivoira
E
.
Citalopram versus sertraline in late-life nonmajor clinically significant depression: a 1-year follow-up clinical trial.
J Clin Psychiatry
2005
66
360
9
PubMed
CrossRef

PubMed
Kasper
S
,
de Swart
H
,
Friis Andersen
H
.
Escitalopram in the treatment of depressed elderly patients.
Am J Geriatr Psychiatry
2005
13
884
91
PubMed
CrossRef

PubMed
Schne
W
,
Ludwig
M
.
A double-blind study of paroxetine compared with fluoxetine in geriatric patients with major depression.
J Clin Psychopharmacol
1993
13
34S
39S
PubMed
PubMed
Geretsegger
C
,
Bhmer
F
,
Ludwig
M
.
Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects.
Int Clin Psychopharmacol
1994
9
25
9
PubMed
CrossRef

PubMed
Cassano
GB
,
Puca
F
,
Scapicchio
PL
,
Trabucchi
M
.
Italian Study Group on Depression in Elderly Patients
Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients.
J Clin Psychiatry
2002
63
396
402
PubMed
CrossRef

PubMed
Rossini
D
,
Serretti
A
,
Franchini
L
,
Mandelli
L
,
Smeraldi
E
,
De Ronchi
D
.
Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.
J Clin Psychopharmacol
2005
25
471
5
PubMed
CrossRef

PubMed
Allard
P
,
Gram
L
,
Timdahl
K
,
Behnke
K
,
Hanson
M
,
Sgaard
J
.
Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram.
Int J Geriatr Psychiatry
2004
19
1123
30
PubMed
CrossRef

PubMed
Oslin
DW
,
Ten Have
TR
,
Streim
JE
,
Datto
CJ
,
Weintraub
D
,
DiFilippo
S
.
Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.
J Clin Psychiatry
2003
64
875
82
PubMed
CrossRef

PubMed
Thase
ME
,
Entsuah
R
,
Cantillon
M
,
Kornstein
SG
.
Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions.
J Womens Health (Larchmt)
2005
14
609
16
PubMed
CrossRef

PubMed
Entsuah
AR
,
Huang
H
,
Thase
ME
.
Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo.
J Clin Psychiatry
2001
62
869
77
PubMed
CrossRef

PubMed
Rapaport
MH
,
Schneider
LS
,
Dunner
DL
,
Davies
JT
,
Pitts
CD
.
Efficacy of controlled-release paroxetine in the treatment of late-life depression.
J Clin Psychiatry
2003
64
1065
74
PubMed
CrossRef

PubMed
Tollefson
GD
,
Bosomworth
JC
,
Heiligenstein
JH
,
Potvin
JH
,
Holman
S
.
A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. The Fluoxetine Collaborative Study Group.
Int Psychogeriatr
1995
7
89
104
PubMed
CrossRef

PubMed
Tollefson
GD
,
Holman
SL
.
Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression.
Int Clin Psychopharmacol
1993
8
253
9
PubMed
CrossRef

PubMed
Small
GW
,
Birkett
M
,
Meyers
BS
,
Koran
LM
,
Bystritsky
A
,
Nemeroff
CB
.
Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group.
J Am Geriatr Soc
1996
44
1220
5
PubMed
CrossRef

PubMed
Schneider
LS
,
Nelson
JC
,
Clary
CM
,
Newhouse
P
,
Krishnan
KR
,
Shiovitz
T
.
Sertraline Elderly Depression Study Group
An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression.
Am J Psychiatry
2003
160
1277
85
PubMed
CrossRef

PubMed
Sheikh
JI
,
Cassidy
EL
,
Doraiswamy
PM
,
Salomon
RM
,
Hornig
M
,
Holland
PJ
.
Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness.
J Am Geriatr Soc
2004
52
86
92
PubMed
CrossRef

PubMed
Roose
SP
,
Sackeim
HA
,
Krishnan
KR
,
Pollock
BG
,
Alexopoulos
G
,
Lavretsky
H
.
Old-Old Depression Study Group
Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.
Am J Psychiatry
2004
161
2050
9
PubMed
CrossRef

PubMed
Kennedy
SH
,
Eisfeld
BS
,
Dickens
SE
,
Bacchiochi
JR
,
Bagby
RM
.
Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine.
J Clin Psychiatry
2000
61
276
81
PubMed
CrossRef

PubMed
Morishita
S
,
Arita
S
.
Differential effects of milnacipran, fluvoxamine and paroxetine for depression, especially in gender.
Eur Psychiatry
2003
18
418
20
PubMed
CrossRef

PubMed
Wagner
GJ
,
Maguen
S
,
Rabkin
JG
.
Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients.
Psychiatr Serv
1998
49
239
40
PubMed
CrossRef

PubMed
Ferrando
SJ
,
Goldman
JD
,
Charness
WE
.
Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms.
Gen Hosp Psychiatry
1997
19
89
97
PubMed
CrossRef

PubMed
Rabkin
JG
,
Wagner
GJ
,
McElhiney
MC
,
Rabkin
R
,
Lin
SH
.
Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial.
J Clin Psychopharmacol
2004
24
379
85
PubMed
CrossRef

PubMed
Rabkin
JG
,
Wagner
GJ
,
Rabkin
R
.
Fluoxetine treatment for depression in patients with HIV and AIDS: a randomized, placebo-controlled trial.
Am J Psychiatry
1999
156
101
7
PubMed
CrossRef

PubMed
Gual
A
,
Balcells
M
,
Torres
M
,
Madrigal
M
,
Diez
T
,
Serrano
L
.
Sertraline for the prevention of relapse in detoxicated alcohol dependent patients with a comorbid depressive disorder: a randomized, controlled trial.
Alcohol Alcohol
2003
38
619
25
PubMed
CrossRef

PubMed
Hernandez-Avila
CA
,
Modesto-Lowe
V
,
Feinn
R
,
Kranzler
HR
.
Nefazodone treatment of comorbid alcohol dependence and major depression.
Alcohol Clin Exp Res
2004
28
433
40
PubMed
CrossRef

PubMed
Moak
DH
,
Anton
RF
,
Latham
PK
,
Voronin
KE
,
Waid
RL
,
Durazo-Arvizu
R
.
Sertraline and cognitive behavioral therapy for depressed alcoholics: results of a placebo-controlled trial.
J Clin Psychopharmacol
2003
23
553
62
PubMed
CrossRef

PubMed
Lyketsos
CG
,
DelCampo
L
,
Steinberg
M
,
Miles
Q
,
Steele
CD
,
Munro
C
.
Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.
Arch Gen Psychiatry
2003
60
737
46
PubMed
CrossRef

PubMed
Magai
C
,
Kennedy
G
,
Cohen
CI
,
Gomberg
D
.
A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer's disease.
Am J Geriatr Psychiatry
2000
8
66
74
PubMed
CrossRef

PubMed
Nyth
AL
,
Gottfries
CG
,
Lyby
K
,
Smedegaard-Andersen
L
,
Gylding-Sabroe
J
,
Kristensen
M
.
A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia.
Acta Psychiatr Scand
1992
86
138
45
PubMed
CrossRef

PubMed
Roscoe
JA
,
Morrow
GR
,
Hickok
JT
,
Mustian
KM
,
Griggs
JJ
,
Matteson
SE
.
Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy.
Breast Cancer Res Treat
2005
89
243
9
PubMed
CrossRef

PubMed
Glassman
AH
,
O'Connor
CM
,
Califf
RM
,
Swedberg
K
,
Schwartz
P
,
Bigger
JT
Jr
.
Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group
Sertraline treatment of major depression in patients with acute MI or unstable angina.
JAMA
2002
288
701
9
PubMed
CrossRef

PubMed
Krishnan
KR
,
Doraiswamy
PM
,
Clary
CM
.
Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline.
Prog Neuropsychopharmacol Biol Psychiatry
2001
25
347
61
PubMed
CrossRef

PubMed
Strik
JJ
,
Honig
A
,
Lousberg
R
,
Lousberg
AH
,
Cheriex
EC
,
Tuynman-Qua
HG
.
Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial.
Psychosom Med
2000
62
783
9
PubMed
CrossRef

PubMed
Andersen
G
,
Vestergaard
K
,
Lauritzen
L
.
Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.
Stroke
1994
25
1099
104
PubMed
CrossRef

PubMed
Murray
V
,
von Arbin
M
,
Bartfai
A
,
Berggren
AL
,
Landtblom
AM
,
Lundmark
J
.
Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression.
J Clin Psychiatry
2005
66
708
16
PubMed
CrossRef

PubMed
Schmitz
JM
,
Averill
P
,
Stotts
AL
,
Moeller
FG
,
Rhoades
HM
,
Grabowski
J
.
Fluoxetine treatment of cocaine-dependent patients with major depressive disorder.
Drug Alcohol Depend
2001
63
207
14
PubMed
CrossRef

PubMed
Petrakis
I
,
Carroll
KM
,
Nich
C
,
Gordon
L
,
Kosten
T
,
Rounsaville
B
.
Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts.
Drug Alcohol Depend
1998
50
221
6
PubMed
CrossRef

PubMed
Bush
DE
,
Ziegelstein
RC
,
Patel
UV
,
Thombs
BD
,
Ford
DE
,
Fauerbach
JA
.
Post-myocardial infarction depression.
Evid Rep Technol Assess (Summ)
2005
1
8
PubMed
.
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.
Washington, DC
American Psychiatric Assoc
2000
Kocsis
JH
,
Zisook
S
,
Davidson
J
,
Shelton
R
,
Yonkers
K
,
Hellerstein
DJ
.
Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: psychosocial outcomes.
Am J Psychiatry
1997
154
390
5
PubMed
CrossRef

PubMed
Thase
ME
,
Fava
M
,
Halbreich
U
,
Kocsis
JH
,
Koran
L
,
Davidson
J
.
A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.
Arch Gen Psychiatry
1996
53
777
84
PubMed
CrossRef

PubMed
Williams
JW
Jr
,
Barrett
J
,
Oxman
T
,
Frank
E
,
Katon
W
,
Sullivan
M
.
Treatment of dysthymia and minor depression in primary care: A randomized, controlled trial in older adults.
JAMA
2000
284
1519
26
PubMed
CrossRef

PubMed
Barrett
JE
,
Williams
JW
Jr
,
Oxman
TE
,
Frank
E
,
Katon
W
,
Sullivan
M
.
Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years.
J Fam Pract
2001
50
405
12
PubMed
PubMed
Judd
LL
,
Rapaport
MH
,
Yonkers
KA
,
Rush
AJ
,
Frank
E
,
Thase
ME
.
Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder.
Am J Psychiatry
2004
161
1864
71
PubMed
CrossRef

PubMed
Kavoussi
RJ
,
Segraves
RT
,
Hughes
AR
,
Ascher
JA
,
Johnston
JA
.
Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients.
J Clin Psychiatry
1997
58
532
7
PubMed
CrossRef

PubMed
Cipriani
A
,
Barbui
C
,
Brambilla
P
,
Furukawa
TA
,
Hotopf
M
,
Geddes
JR
.
Are all antidepressants really the same? The case of fluoxetine: a systematic review.
J Clin Psychiatry
2006
67
850
64
PubMed
CrossRef

PubMed
Rush
AJ
,
Trivedi
MH
,
Wisniewski
SR
,
Nierenberg
AA
,
Stewart
JW
,
Warden
D
.
Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.
Am J Psychiatry
2006
163
1905
17
PubMed
CrossRef

PubMed
Aguglia
E
,
Casacchia
M
,
Cassano
GB
,
Faravelli
C
,
Ferrari
G
,
Giordano
P
.
Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression.
Int Clin Psychopharmacol
1993
8
197
202
PubMed
CrossRef

PubMed
Amini
H
,
Aghayan
S
,
Jalili
SA
,
Akhondzadeh
S
,
Yahyazadeh
O
,
Pakravan-Nejad
M
.
Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.
J Clin Pharm Ther
2005
30
133
8
PubMed
CrossRef

PubMed
Brown
ES
,
Vigil
L
,
Khan
DA
,
Liggin
JD
,
Carmody
TJ
,
Rush
AJ
.
A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study.
Biol Psychiatry
2005
58
865
70
PubMed
CrossRef

PubMed
Byerley
WF
,
Reimherr
FW
,
Wood
DR
,
Grosser
BI
.
Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression.
J Clin Psychopharmacol
1988
8
112
5
PubMed
CrossRef

PubMed
Claghorn
JL
,
Lesem
MD
.
A double-blind placebo-controlled study of Org 3770 in depressed outpatients.
J Affect Disord
1995
34
165
71
PubMed
CrossRef

PubMed
Claghorn
JL
,
Earl
CQ
,
Walczak
DD
,
Stoner
KA
,
Wong
LF
,
Kanter
D
.
Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients.
J Clin Psychopharmacol
1996
16
113
20
PubMed
CrossRef

PubMed
Claghorn
JL
.
The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients.
J Clin Psychiatry
1992
53
33
5
PubMed
PubMed
Cohn
JB
,
Crowder
JE
,
Wilcox
CS
,
Ryan
PJ
.
A placebo- and imipramine-controlled study of paroxetine.
Psychopharmacol Bull
1990
26
185
9
PubMed
PubMed
Cohn
JB
,
Wilcox
CS
.
Paroxetine in major depression: a double-blind trial with imipramine and placebo.
J Clin Psychiatry
1992
53
52
6
PubMed
PubMed
Corrigan
MH
,
Denahan
AQ
,
Wright
CE
,
Ragual
RJ
,
Evans
DL
.
Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.
Depress Anxiety
2000
11
58
65
PubMed
CrossRef

PubMed
Croft
H
,
Houser
TL
,
Jamerson
BD
,
Leadbetter
R
,
Bolden-Watson
C
,
Donahue
R
.
Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks.
Clin Ther
2002
24
662
72
PubMed
CrossRef

PubMed
Dunbar
GC
,
Cohn
JB
,
Fabre
LF
,
Feighner
JP
,
Fieve
RR
,
Mendels
J
.
A comparison of paroxetine, imipramine and placebo in depressed out-patients.
Br J Psychiatry
1991
159
394
8
PubMed
CrossRef

PubMed
Dunbar
GC
,
Claghorn
JL
,
Kiev
A
,
Rickels
K
,
Smith
WT
.
A comparison of paroxetine and placebo in depressed outpatients.
Acta Psychiatr Scand
1993
87
302
5
PubMed
CrossRef

PubMed
Elliott
AJ
,
Uldall
KK
,
Bergam
K
,
Russo
J
,
Claypoole
K
,
Roy-Byrne
PP
.
Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients.
Am J Psychiatry
1998
155
367
72
PubMed
PubMed
Evans
M
,
Hammond
M
,
Wilson
K
,
Lye
M
,
Copeland
J
.
Placebo-controlled treatment trial of depression in elderly physically ill patients.
Int J Geriatr Psychiatry
1997
12
817
24
PubMed
CrossRef

PubMed
Fabre
L
,
Birkhimer
LJ
,
Zaborny
BA
,
Wong
LF
,
Kapik
BM
.
Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients.
Int Clin Psychopharmacol
1996
11
119
27
PubMed
PubMed
Fabre
LF
,
Abuzzahab
FS
,
Amin
M
,
Claghorn
JL
,
Mendels
J
,
Petrie
WM
.
Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo.
Biol Psychiatry
1995
38
592
602
PubMed
CrossRef

PubMed
Fabre
LF
.
A 6-week, double-blind trial of paroxetine, imipramine, and placebo in depressed outpatients.
J Clin Psychiatry
1992
53
40
3
PubMed
PubMed
Fabre
LF
,
Putman
HP
3rd
.
A fixed-dose clinical trial of fluoxetine in outpatients with major depression.
J Clin Psychiatry
1987
48
406
8
PubMed
PubMed
Falk
WE
,
Rosenbaum
JF
,
Otto
MW
,
Zusky
PM
,
Weilburg
JB
,
Nixon
RA
.
Fluoxetine versus trazodone in depressed geriatric patients.
J Geriatr Psychiatry Neurol
1989
2
208
14
PubMed
CrossRef

PubMed
Fava
M
,
Alpert
J
,
Nierenberg
AA
,
Mischoulon
D
,
Otto
MW
,
Zajecka
J
.
A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.
J Clin Psychopharmacol
2005
25
441
7
PubMed
CrossRef

PubMed
Fava
M
,
Mulroy
R
,
Alpert
J
,
Nierenberg
AA
,
Rosenbaum
JF
.
Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine.
Am J Psychiatry
1997
154
1760
2
PubMed
CrossRef

PubMed
Feighner
JP
.
A double-blind comparison of paroxetine, imipramine and placebo in depressed outpatients.
Int Clin Psychopharmacol
1992
6
31
5
PubMed
CrossRef

PubMed
Feighner
JP
,
Boyer
WF
.
Paroxetine in the treatment of depression: a comparison with imipramine and placebo.
J Clin Psychiatry
1992
53
44
7
PubMed
PubMed
Feighner
JP
,
Cohn
JB
,
Fabre
LF
Jr
,
Fieve
RR
,
Mendels
J
,
Shrivastava
RK
.
A study comparing paroxetine placebo and imipramine in depressed patients.
J Affect Disord
1993
28
71
9
PubMed
CrossRef

PubMed
Feighner
J
,
Targum
SD
,
Bennett
ME
,
Roberts
DL
,
Kensler
TT
,
D'Amico
MF
.
A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression.
J Clin Psychiatry
1998
59
246
53
PubMed
CrossRef

PubMed
Flament
MF
,
Lane
R
.
Acute antidepressant response to fluoxetine and sertraline in psychiatric outpatients with psychomotor agitation.
Int J Psychiatry Clin Pract
2001
5
103
9
CrossRef

PubMed
Gilaberte
I
,
Montejo
AL
,
de la Gandara
J
,
Perez-Sola
V
,
Bernardo
M
,
Massana
J
.
Fluoxetine Long-Term Study Group
Fluoxetine in the prevention of depressive recurrences: a double-blind study.
J Clin Psychopharmacol
2001
21
417
24
PubMed
CrossRef

PubMed
Grigoriadis
S
,
Kennedy
SH
,
Bagby
RM
.
A comparison of antidepressant response in younger and older women.
J Clin Psychopharmacol
2003
23
405
7
PubMed
CrossRef

PubMed
Glseren
L
,
Glseren
S
,
Hekimsoy
Z
,
Mete
L
.
Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients.
Arch Med Res
2005
36
159
65
PubMed
CrossRef

PubMed
Kennedy
SH
,
Fulton
KA
,
Bagby
RM
,
Greene
AL
,
Cohen
NL
,
Rafi-Tari
S
.
Sexual function during bupropion or paroxetine treatment of major depressive disorder.
Can J Psychiatry
2006
51
234
42
PubMed
CrossRef

PubMed
Lapierre
YD
,
Browne
M
,
Horn
E
,
Oyewumi
LK
,
Sarantidis
D
,
Roberts
N
.
Treatment of major affective disorder with fluvoxamine.
J Clin Psychiatry
1987
48
65
8
PubMed
PubMed
March
JS
,
Kobak
KA
,
Jefferson
JW
,
Mazza
J
,
Greist
JH
.
A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression.
J Clin Psychiatry
1990
51
200
2
PubMed
PubMed
McGrath
PJ
,
Stewart
JW
,
Janal
MN
,
Petkova
E
,
Quitkin
FM
,
Klein
DF
.
A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression.
Am J Psychiatry
2000
157
344
50
PubMed
CrossRef

PubMed
Mesters
P
,
Cosyns
P
,
Dejaiffe
G
,
Fanielle
J
,
Gilles
C
,
Godderis
J
.
Assessment of quality of life in the treatment of major depressive disorder with fluoxetine, 20 mg, in ambulatory patients aged over 60 years.
Int Clin Psychopharmacol
1993
8
337
40
PubMed
CrossRef

PubMed
Montgomery
SA
,
Rasmussen
JG
,
Lyby
K
,
Connor
P
,
Tanghj
P
.
Dose response relationship of citalopram 20 mg, citalopram 40 mg and placebo in the treatment of moderate and severe depression.
Int Clin Psychopharmacol
1992
6
65
70
PubMed
CrossRef

PubMed
Muijen
M
,
Roy
D
,
Silverstone
T
,
Mehmet
A
,
Christie
M
.
A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients.
Acta Psychiatr Scand
1988
78
384
90
PubMed
CrossRef

PubMed
Petracca
GM
,
Chemerinski
E
,
Starkstein
SE
.
A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease.
Int Psychogeriatr
2001
13
233
40
PubMed
CrossRef

PubMed
Ravindran
AV
,
Teehan
MD
,
Bakish
D
.
The impact of sertraline, desipramine, and placebo on psychomotor functioning in depression.
Hum Psychopharmacol
1995
10
4
273
281
CrossRef
Reimherr
FW
,
Cunningham
LA
,
Batey
SR
,
Johnston
JA
,
Ascher
JA
.
A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients.
Clin Ther
1998
20
505
16
PubMed
CrossRef

PubMed
Rickels
K
,
Schweizer
E
,
Clary
C
,
Fox
I
,
Weise
C
.
Nefazodone and imipramine in major depression: a placebo-controlled trial.
Br J Psychiatry
1994
164
802
5
PubMed
CrossRef

PubMed
Rickels
K
,
Case
WG
.
Trazodone in depressed outpatients.
Am J Psychiatry
1982
139
803
6
PubMed
CrossRef

PubMed
Rickels
K
,
Amsterdam
J
,
Clary
C
,
Fox
I
,
Schweizer
E
,
Weise
C
.
The efficacy and safety of paroxetine compared with placebo in outpatients with major depression.
J Clin Psychiatry
1992
53
30
2
PubMed
PubMed
Rosenbaum
JF
,
Fava
M
,
Hoog
SL
,
Ascroft
RC
,
Krebs
WB
.
Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial.
Biol Psychiatry
1998
44
77
87
PubMed
CrossRef

PubMed
Roth
D
,
Mattes
J
,
Sheehan
KH
,
Sheehan
DV
.
A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression.
Prog Neuropsychopharmacol Biol Psychiatry
1990
14
929
39
PubMed
CrossRef

PubMed
Roy-Byrne
PP
,
Pages
KP
,
Russo
JE
,
Jaffe
C
,
Blume
AW
,
Kingsley
E
.
Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial.
J Clin Psychopharmacol
2000
20
129
36
PubMed
CrossRef

PubMed
Rudolph
RL
,
Fabre
LF
,
Feighner
JP
,
Rickels
K
,
Entsuah
R
,
Derivan
AT
.
A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression.
J Clin Psychiatry
1998
59
116
22
PubMed
CrossRef

PubMed
Schweizer
E
,
Weise
C
,
Clary
C
,
Fox
I
,
Rickels
K
.
Placebo-controlled trial of venlafaxine for the treatment of major depression.
J Clin Psychopharmacol
1991
11
233
6
PubMed
CrossRef

PubMed
Smith
WT
,
Glaudin
V
,
Panagides
J
,
Gilvary
E
.
Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.
Psychopharmacol Bull
1990
26
191
6
PubMed
PubMed
Smith
WT
,
Glaudin
V
.
A placebo-controlled trial of paroxetine in the treatment of major depression.
J Clin Psychiatry
1992
53
36
9
PubMed
PubMed
Stahl
SM
.
Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.
Biol Psychiatry
2000
48
894
901
PubMed
CrossRef

PubMed
Thase
ME
,
Entsuah
AR
,
Rudolph
RL
.
Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors.
Br J Psychiatry
2001
178
234
41
PubMed
CrossRef

PubMed
Tollefson
GD
,
Rampey
AH
Jr
,
Beasley
CM
Jr
,
Enas
GG
,
Potvin
JH
.
Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression.
J Clin Psychopharmacol
1994
14
163
9
PubMed
PubMed
Beasley
CM
Jr
,
Dornseif
BE
,
Bosomworth
JC
,
Sayler
ME
,
Rampey
AH
Jr
,
Heiligenstein
JH
.
Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.
BMJ
1991
303
685
92
PubMed
CrossRef

PubMed
Vartiainen
H
,
Leinonen
E
.
Double-blind study of mirtazapine and placebo in hospitalized patients with major depression.
Eur Neuropsychopharmacol
1994
4
145
50
PubMed
CrossRef

PubMed
Wade
A
,
Crawford
GM
,
Angus
M
,
Wilson
R
,
Hamilton
L
.
A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care.
Int Clin Psychopharmacol
2003
18
133
41
PubMed
PubMed
Wernicke
JF
,
Dunlop
SR
,
Dornseif
BE
,
Zerbe
RL
.
Fixed-dose fluoxetine therapy for depression.
Psychopharmacol Bull
1987
23
164
8
PubMed
PubMed
Winokur
A
,
DeMartinis
NA
3rd
,
McNally
DP
,
Gary
EM
,
Cormier
JL
,
Gary
KA
.
Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia.
J Clin Psychiatry
2003
64
1224
9
PubMed
CrossRef

PubMed
Zanardi
R
,
Franchini
L
,
Gasperini
M
,
Perez
J
,
Smeraldi
E
.
Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression.
Am J Psychiatry
1996
153
1631
3
PubMed
CrossRef

PubMed
Baldwin
DS
,
Cooper
JA
,
Huusom
AK
,
Hindmarch
I
.
A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder.
Int Clin Psychopharmacol
2006
21
159
69
PubMed
CrossRef

PubMed
Boulenger
JP
,
Huusom
AK
,
Florea
I
,
Baekdal
T
,
Sarchiapone
M
.
A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients.
Curr Med Res Opin
2006
22
1331
41
PubMed
CrossRef

PubMed
Dalery
J
,
Honig
A
.
Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.
Hum Psychopharmacol
2003
18
379
84
PubMed
CrossRef

PubMed
De Wilde
J
,
Spiers
R
,
Mertens
C
,
Bartholom
F
,
Schotte
G
,
Leyman
S
.
A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients.
Acta Psychiatr Scand
1993
87
141
5
PubMed
CrossRef

PubMed
Ekselius
L
,
von Knorring
L
.
Effect on sexual function of long-term treatment with selective serotonin reuptake inhibitors in depressed patients treated in primary care.
J Clin Psychopharmacol
2001
21
154
60
PubMed
CrossRef

PubMed
Fava
M
,
Judge
R
,
Hoog
SL
,
Nilsson
ME
,
Koke
SC
.
Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment.
J Clin Psychiatry
2000
61
863
7
PubMed
CrossRef

PubMed
Haffmans
PM
,
Timmerman
L
,
Hoogduin
CA
.
Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group.
Int Clin Psychopharmacol
1996
11
157
64
PubMed
CrossRef

PubMed
Nemeroff
CB
,
Ninan
PT
,
Ballenger
J
,
Lydiard
RB
,
Feighner
J
,
Patterson
WM
.
Double-blind multicenter comparison of fluvoxamine versus sertraline in the treatment of depressed outpatients.
Depression
1995
3
163
9
CrossRef
Patris
M
,
Bouchard
JM
,
Bougerol
T
,
Charbonnier
JF
,
Chevalier
JF
,
Clerc
G
.
Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.
Int Clin Psychopharmacol
1996
11
129
36
PubMed
PubMed
Rapaport
M
,
Coccaro
E
,
Sheline
Y
,
Perse
T
,
Holland
P
,
Fabre
L
.
A comparison of fluvoxamine and fluoxetine in the treatment of major depression.
J Clin Psychopharmacol
1996
16
373
8
PubMed
CrossRef

PubMed
Tignol
J
.
A double-blind, randomized, fluoxetine-controlled, multicenter study of paroxetine in the treatment of depression.
J Clin Psychopharmacol
1993
13
18S
22S
PubMed
CrossRef

PubMed
Ventura
D
,
Armstrong
EP
,
Skrepnek
GH
,
Haim Erder
M
.
Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial.
Curr Med Res Opin
2007
23
245
50
PubMed
CrossRef

PubMed
Balls
C
,
Quiros
G
,
De Flores
T
,
de la Torre
J
,
Palao
D
,
Rojo
L
.
The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorder or dysthymia.
Int Clin Psychopharmacol
2000
15
43
8
PubMed
CrossRef

PubMed
Goldstein
DJ
,
Mallinckrodt
C
,
Lu
Y
,
Demitrack
MA
.
Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial.
J Clin Psychiatry
2002
63
225
31
PubMed
CrossRef

PubMed
Mehtonen
OP
,
Sgaard
J
,
Roponen
P
,
Behnke
K
.
Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group.
J Clin Psychiatry
2000
61
95
100
PubMed
CrossRef

PubMed
Montgomery
SA
,
Huusom
AK
,
Bothmer
J
.
A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder.
Neuropsychobiology
2004
50
57
64
PubMed
CrossRef

PubMed
Nierenberg
AA
,
Greist
JH
,
Mallinckrodt
CH
,
Prakash
A
,
Sambunaris
A
,
Tollefson
GD
.
Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study.
Curr Med Res Opin
2007
23
401
16
PubMed
CrossRef

PubMed
Schatzberg
A
,
Roose
S
.
A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression.
Am J Geriatr Psychiatry
2006
14
361
70
PubMed
CrossRef

PubMed
Shelton
RC
,
Haman
KL
,
Rapaport
MH
,
Kiev
A
,
Smith
WT
,
Hirschfeld
RM
.
A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.
J Clin Psychiatry
2006
67
1674
81
PubMed
CrossRef

PubMed
Silverstone
PH
,
Ravindran
A
.
Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group.
J Clin Psychiatry
1999
60
22
8
PubMed
CrossRef

PubMed
Feiger
A
,
Kiev
A
,
Shrivastava
RK
,
Wisselink
PG
,
Wilcox
CS
.
Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction.
J Clin Psychiatry
1996
57
53
62
PubMed
PubMed
Kasper
S
,
Olivieri
L
,
Di Loreto
G
,
Dionisio
P
.
A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder.
Curr Med Res Opin
2005
21
1139
46
PubMed
CrossRef

PubMed
Munizza
C
,
Olivieri
L
,
Di Loreto
G
,
Dionisio
P
.
A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.
Curr Med Res Opin
2006
22
1703
13
PubMed
CrossRef

PubMed
Perry
PJ
,
Garvey
MJ
,
Kelly
MW
,
Cook
BL
,
Dunner
FJ
,
Winokur
G
.
A comparative trial of fluoxetine versus trazodone in outpatients with major depression.
J Clin Psychiatry
1989
50
290
4
PubMed
PubMed
Halikas
JA
.
Org 3770 (mirtazapine) versus trazodone: A placebo controlled trial in depressed elderly patients.
Hum Psychopharmacol
1995
10
S125
33
CrossRef
van Moffaert
M
,
de Wilde
J
,
Vereecken
A
,
Dierick
M
,
Evrard
JL
,
Wilmotte
J
.
Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression.
Int Clin Psychopharmacol
1995
10
3
9
PubMed
CrossRef

PubMed
Weisler
RH
,
Johnston
JA
,
Lineberry
CG
,
Samara
B
,
Branconnier
RJ
,
Billow
AA
.
Comparison of bupropion and trazodone for the treatment of major depression.
J Clin Psychopharmacol
1994
14
170
9
PubMed
CrossRef

PubMed
Weihs
KL
,
Houser
TL
,
Batey
SR
,
Ascher
JA
,
Bolden-Watson
C
,
Donahue
RM
.
Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression.
Biol Psychiatry
2002
51
753
61
PubMed
CrossRef

PubMed
Hochstrasser
B
,
Isaksen
PM
,
Koponen
H
,
Lauritzen
L
,
Mahnert
FA
,
Rouillon
F
.
Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy.
Br J Psychiatry
2001
178
304
10
PubMed
CrossRef

PubMed
Klysner
R
,
Bent-Hansen
J
,
Hansen
HL
,
Lunde
M
,
Pleidrup
E
,
Poulsen
DL
.
Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy.
Br J Psychiatry
2002
181
29
35
PubMed
CrossRef

PubMed
Kornstein
SG
,
Bose
A
,
Li
D
,
Saikali
KG
,
Gandhi
C
.
Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial.
J Clin Psychiatry
2006
67
1767
75
PubMed
CrossRef

PubMed
Montgomery
SA
,
Rasmussen
JG
.
Citalopram 20 mg, citalopram 40 mg and placebo in the prevention of relapse of major depression.
Int Clin Psychopharmacol
1992
6
71
3
PubMed
CrossRef

PubMed
Robert
P
,
Montgomery
SA
.
Citalopram in doses of 20-60 mg is effective in depression relapse prevention: a placebo-controlled 6 month study.
Int Clin Psychopharmacol
1995
10
29
35
PubMed
CrossRef

PubMed
Rapaport
MH
,
Bose
A
,
Zheng
H
.
Escitalopram continuation treatment prevents relapse of depressive episodes.
J Clin Psychiatry
2004
65
44
9
PubMed
CrossRef

PubMed
Schmidt
ME
,
Fava
M
,
Robinson
JM
,
Judge
R
.
The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder.
J Clin Psychiatry
2000
61
851
7
PubMed
CrossRef

PubMed
Dinan
TG
.
Efficacy and safety of weekly treatment with enteric-coated fluoxetine in patients with major depressive disorder.
J Clin Psychiatry
2001
62
48
52
PubMed
PubMed
Reimherr
FW
,
Amsterdam
JD
,
Quitkin
FM
,
Rosenbaum
JF
,
Fava
M
,
Zajecka
J
.
Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment.
Am J Psychiatry
1998
155
1247
53
PubMed
CrossRef

PubMed
Michelson
D
,
Amsterdam
JD
,
Quitkin
FM
,
Reimherr
FW
,
Rosenbaum
JF
,
Zajecka
J
.
Changes in weight during a 1-year trial of fluoxetine.
Am J Psychiatry
1999
156
1170
6
PubMed
PubMed
Terra
JL
,
Montgomery
SA
.
Fluvoxamine prevents recurrence of depression: results of a long-term, double-blind, placebo-controlled study.
Int Clin Psychopharmacol
1998
13
55
62
PubMed
CrossRef

PubMed
Thase
ME
,
Nierenberg
AA
,
Keller
MB
,
Panagides
J
.
Relapse Prevention Study Group
Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.
J Clin Psychiatry
2001
62
782
8
PubMed
CrossRef

PubMed
Gelenberg
AJ
,
Trivedi
MH
,
Rush
AJ
,
Thase
ME
,
Howland
R
,
Klein
DN
.
Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression.
Biol Psychiatry
2003
54
806
17
PubMed
CrossRef

PubMed
Feiger
AD
,
Bielski
RJ
,
Bremner
J
,
Heiser
JF
,
Trivedi
M
,
Wilcox
CS
.
Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.
Int Clin Psychopharmacol
1999
14
19
28
PubMed
CrossRef

PubMed
Claghorn
JL
,
Feighner
JP
.
A double-blind comparison of paroxetine with imipramine in the long-term treatment of depression.
J Clin Psychopharmacol
1993
13
23S
27S
PubMed
CrossRef

PubMed
Montgomery
SA
,
Dunbar
G
.
Paroxetine is better than placebo in relapse prevention and the prophylaxis of recurrent depression.
Int Clin Psychopharmacol
1993
8
189
95
PubMed
CrossRef

PubMed
Reynolds
CF
3rd
,
Dew
MA
,
Pollock
BG
,
Mulsant
BH
,
Frank
E
,
Miller
MD
.
Maintenance treatment of major depression in old age.
N Engl J Med
2006
354
1130
8
PubMed
CrossRef

PubMed
Lpine
JP
,
Caillard
V
,
Bisserbe
JC
,
Troy
S
,
Hotton
JM
,
Boyer
P
.
A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder.
Am J Psychiatry
2004
161
836
42
PubMed
CrossRef

PubMed
Doogan
DP
,
Caillard
V
.
Sertraline in the prevention of depression.
Br J Psychiatry
1992
160
217
22
PubMed
CrossRef

PubMed
Keller
MB
,
Kocsis
JH
,
Thase
ME
,
Gelenberg
AJ
,
Rush
AJ
,
Koran
L
.
Maintenance phase efficacy of sertraline for chronic depression: a randomized, controlled trial.
JAMA
1998
280
1665
72
PubMed
CrossRef

PubMed
Kocsis
JH
,
Schatzberg
A
,
Rush
AJ
,
Klein
DN
,
Howland
R
,
Gniwesch
L
.
Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo.
Arch Gen Psychiatry
2002
59
723
8
PubMed
CrossRef

PubMed
Lustman
PJ
,
Clouse
RE
,
Nix
BD
,
Freedland
KE
,
Rubin
EH
,
McGill
JB
.
Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.
Arch Gen Psychiatry
2006
63
521
9
PubMed
CrossRef

PubMed
Wilson
KC
,
Mottram
PG
,
Ashworth
L
,
Abou-Saleh
MT
.
Older community residents with depression: long-term treatment with sertraline. Randomised, double-blind, placebo-controlled study.
Br J Psychiatry
2003
182
492
7
PubMed
CrossRef

PubMed
Venlafaxine 335 Study Group
Venlafaxine versus placebo in the preventive treatment of recurrent major depression.
J Clin Psychiatry
2004
65
328
36
PubMed
CrossRef

PubMed
Simon
JS
,
Aguiar
LM
,
Kunz
NR
,
Lei
D
.
Extended-release venlafaxine in relapse prevention for patients with major depressive disorder.
J Psychiatr Res
2004
38
249
57
PubMed
CrossRef

PubMed
Joliat
MJ
,
Schmidt
ME
,
Fava
M
,
Zhang
S
,
Michelson
D
,
Trapp
NJ
.
Long-term treatment outcomes of depression with associated anxiety: efficacy of continuation treatment with fluoxetine.
J Clin Psychiatry
2004
65
373
8
PubMed
CrossRef

PubMed
Khan
A
,
Upton
GV
,
Rudolph
RL
,
Entsuah
R
,
Leventer
SM
.
The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group.
J Clin Psychopharmacol
1998
18
19
25
PubMed
CrossRef

PubMed
Gillin
JC
,
Rapaport
M
,
Erman
MK
,
Winokur
A
,
Albala
BJ
.
A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial.
J Clin Psychiatry
1997
58
185
92
PubMed
CrossRef

PubMed
Mallinckrodt
CH
,
Watkin
JG
,
Liu
C
,
Wohlreich
MM
,
Raskin
J
.
Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features.
BMC Psychiatry
2005
5
1
PubMed
CrossRef

PubMed
Detke
MJ
,
Lu
Y
,
Goldstein
DJ
,
Hayes
JR
,
Demitrack
MA
.
Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial.
J Clin Psychiatry
2002
63
308
15
PubMed
CrossRef

PubMed
Detke
MJ
,
Lu
Y
,
Goldstein
DJ
,
McNamara
RK
,
Demitrack
MA
.
Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression.
J Psychiatr Res
2002
36
383
90
PubMed
CrossRef

PubMed
Brambilla
P
,
Cipriani
A
,
Hotopf
M
,
Barbui
C
.
Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data.
Pharmacopsychiatry
2005
38
69
77
PubMed
CrossRef

PubMed
Greist
J
,
McNamara
RK
,
Mallinckrodt
CH
,
Rayamajhi
JN
,
Raskin
J
.
Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine.
Clin Ther
2004
26
1446
55
PubMed
CrossRef

PubMed
Mackay
FJ
,
Dunn
NR
,
Wilton
LV
,
Pearce
GL
,
Freemantle
SN
,
Mann
RD
.
A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies.
Pharmacoepidemiol Drug Saf
1997
6
235
46
PubMed
CrossRef

PubMed
Mackay
FR
,
Dunn
NR
,
Martin
RM
,
Pearce
GL
,
Freemantle
SN
,
Mann
RD
.
Newer antidepressants: a comparison of tolerability in general practice.
Br J Gen Pract
1999
49
892
6
PubMed
PubMed
Mackay
FJ
,
Dunn
NR
,
Mann
RD
.
Antidepressants and the serotonin syndrome in general practice.
Br J Gen Pract
1999
49
871
4
PubMed
PubMed
Meijer
WE
,
Heerdink
ER
,
van Eijk
JT
,
Leufkens
HG
.
Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands.
Pharmacoepidemiol Drug Saf
2002
11
655
62
PubMed
CrossRef

PubMed
Goldstein
DJ
,
Hamilton
SH
,
Masica
DN
,
Beasley
CM
Jr
.
Fluoxetine in medically stable, depressed geriatric patients: effects on weight.
J Clin Psychopharmacol
1997
17
365
9
PubMed
CrossRef

PubMed
Harto
NE
,
Spera
KF
,
Branconnier
RJ
.
Fluoxetine-induced reduction of body mass in patients with major depressive disorder.
Psychopharmacol Bull
1988
24
220
3
PubMed
PubMed
Judge
R
,
Parry
MG
,
Quail
D
,
Jacobson
JG
.
Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment.
Int Clin Psychopharmacol
2002
17
217
25
PubMed
CrossRef

PubMed
Perahia
DG
,
Kajdasz
DK
,
Desaiah
D
,
Haddad
PM
.
Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder.
J Affect Disord
2005
89
207
12
PubMed
CrossRef

PubMed
Zajecka
J
,
Fawcett
J
,
Amsterdam
J
,
Quitkin
F
,
Reimherr
F
,
Rosenbaum
J
.
Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study.
J Clin Psychopharmacol
1998
18
193
7
PubMed
CrossRef

PubMed
Pedersen
AG
.
Escitalopram and suicidality in adult depression and anxiety.
Int Clin Psychopharmacol
2005
20
139
43
PubMed
CrossRef

PubMed
Clayton
AH
,
Pradko
JF
,
Croft
HA
,
Montano
CB
,
Leadbetter
RA
,
Bolden-Watson
C
.
Prevalence of sexual dysfunction among newer antidepressants.
J Clin Psychiatry
2002
63
357
66
PubMed
CrossRef

PubMed
Clayton
AH
,
Croft
HA
,
Horrigan
JP
,
Wightman
DS
,
Krishen
A
,
Richard
NE
.
Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies.
J Clin Psychiatry
2006
67
736
46
PubMed
CrossRef

PubMed
Delgado
PL
,
Brannan
SK
,
Mallinckrodt
CH
,
Tran
PV
,
McNamara
RK
,
Wang
F
.
Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder.
J Clin Psychiatry
2005
66
686
92
PubMed
CrossRef

PubMed
Ferguson
JM
,
Shrivastava
RK
,
Stahl
SM
,
Hartford
JT
,
Borian
F
,
Ieni
J
.
Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline.
J Clin Psychiatry
2001
62
24
9
PubMed
CrossRef

PubMed
Landn
M
,
Hgberg
P
,
Thase
ME
.
Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine.
J Clin Psychiatry
2005
66
100
6
PubMed
CrossRef

PubMed
Nieuwstraten
CE
,
Dolovich
LR
.
Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression.
Ann Pharmacother
2001
35
1608
13
PubMed
CrossRef

PubMed
Philipp
M
,
Tiller
JW
,
Baier
D
,
Kohnen
R
.
Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults. The Australian and German Study Groups.
Eur Neuropsychopharmacol
2000
10
305
14
PubMed
CrossRef

PubMed
Dunner
DL
,
Zisook
S
,
Billow
AA
,
Batey
SR
,
Johnston
JA
,
Ascher
JA
.
A prospective safety surveillance study for bupropion sustained-release in the treatment of depression.
J Clin Psychiatry
1998
59
366
73
PubMed
CrossRef

PubMed
Johnston
JA
,
Lineberry
CG
,
Ascher
JA
,
Davidson
J
,
Khayrallah
MA
,
Feighner
JP
.
A 102-center prospective study of seizure in association with bupropion.
J Clin Psychiatry
1991
52
450
6
PubMed
PubMed
Whyte
IM
,
Dawson
AH
,
Buckley
NA
.
Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants.
QJM
2003
96
369
74
PubMed
CrossRef

PubMed
Thase
ME
.
Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients.
J Clin Psychiatry
1998
59
502
8
PubMed
CrossRef

PubMed
Thase
ME
,
Tran
PV
,
Wiltse
C
,
Pangallo
BA
,
Mallinckrodt
C
,
Detke
MJ
.
Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine.
J Clin Psychopharmacol
2005
25
132
40
PubMed
CrossRef

PubMed
Buckley
NA
,
McManus
PR
.
Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data.
BMJ
2002
325
1332
3
PubMed
CrossRef

PubMed
Coogan
PF
,
Palmer
JR
,
Strom
BL
,
Rosenberg
L
.
Use of selective serotonin reuptake inhibitors and the risk of breast cancer.
Am J Epidemiol
2005
162
835
8
PubMed
CrossRef

PubMed
Kirby
D
,
Harrigan
S
,
Ames
D
.
Hyponatraemia in elderly psychiatric patients treated with selective serotonin reuptake inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit.
Int J Geriatr Psychiatry
2002
17
231
7
PubMed
CrossRef

PubMed
Thapa
PB
,
Gideon
P
,
Cost
TW
,
Milam
AB
,
Ray
WA
.
Antidepressants and the risk of falls among nursing home residents.
N Engl J Med
1998
339
875
82
PubMed
CrossRef

PubMed
Burt
VK
,
Wohlreich
MM
,
Mallinckrodt
CH
,
Detke
MJ
,
Watkin
JG
,
Stewart
DE
.
Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years.
Psychosomatics
2005
46
345
54
PubMed
CrossRef

PubMed
Kranzler
HR
,
Mueller
T
,
Cornelius
J
,
Pettinati
HM
,
Moak
D
,
Martin
PR
.
Sertraline treatment of co-occurring alcohol dependence and major depression.
J Clin Psychopharmacol
2006
26
13
20
PubMed
CrossRef

PubMed
Addington
D
,
Addington
J
,
Patten
S
,
Remington
G
,
Moamai
J
,
Labelle
A
.
Double-blind, placebo-controlled comparison of the efficacy of sertraline as treatment for a major depressive episode in patients with remitted schizophrenia.
J Clin Psychopharmacol
2002
22
20
5
PubMed
CrossRef

PubMed
Burke
WJ
,
McArthur-Miller
DA
.
Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder.
J Clin Psychiatry
2001
62
38
42
PubMed
PubMed
Claghorn
J
.
A double-blind comparison of paroxetine and placebo in the treatment of depressed outpatients.
Int Clin Psychopharmacol
1992
6
25
30
PubMed
CrossRef

PubMed
Claghorn
JL
,
Kiev
A
,
Rickels
K
,
Smith
WT
,
Dunbar
GC
.
Paroxetine versus placebo: a double-blind comparison in depressed patients.
J Clin Psychiatry
1992
53
434
8
PubMed
PubMed
Cohn
CK
,
Robinson
DS
,
Roberts
DL
,
Schwiderski
UE
,
O'Brien
K
,
Ieni
JR
.
Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression.
J Clin Psychiatry
1996
57
15
8
PubMed
PubMed
Cunningham
LA
.
Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group.
Ann Clin Psychiatry
1997
9
157
64
PubMed
CrossRef

PubMed
Feighner
JP
,
Over
K
.
Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression.
J Clin Psychiatry
1999
60
824
30
PubMed
CrossRef

PubMed
Fontaine
R
,
Ontiveros
A
,
Elie
R
,
Kensler
TT
,
Roberts
DL
,
Kaplita
S
.
A double-blind comparison of nefazodone, imipramine, and placebo in major depression.
J Clin Psychiatry
1994
55
234
41
PubMed
PubMed
Hypericum Depression Trial Study Group
Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized, controlled trial.
JAMA
2002
287
1807
14
PubMed
CrossRef

PubMed
Khan
A
,
Fabre
LF
,
Rudolph
R
.
Venlafaxine in depressed outpatients.
Psychopharmacol Bull
1991
27
141
4
PubMed
PubMed
Lineberry
CG
,
Johnston
JA
,
Raymond
RN
,
Samara
B
,
Feighner
JP
,
Harto
NE
.
A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients.
J Clin Psychiatry
1990
51
194
9
PubMed
PubMed
Lydiard
RB
,
Laird
LK
,
Morton
WA
Jr
,
Steele
TE
,
Kellner
C
,
Laraia
MT
.
Fluvoxamine, imipramine, and placebo in the treatment of depressed outpatients: effects on depression.
Psychopharmacol Bull
1989
25
68
70
PubMed
PubMed
Lydiard
RB
,
Stahl
SM
,
Hertzman
M
,
Harrison
WM
.
A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression.
J Clin Psychiatry
1997
58
484
91
PubMed
CrossRef

PubMed
Mendels
J
,
Johnston
R
,
Mattes
J
,
Riesenberg
R
.
Efficacy and safety of b.i.d. doses of venlafaxine in a dose-response study.
Psychopharmacol Bull
1993
29
169
74
PubMed
PubMed
Mendels
J
,
Reimherr
F
,
Marcus
RN
,
Roberts
DL
,
Francis
RJ
,
Anton
SF
.
A double-blind, placebo-controlled trial of two dose ranges of nefazodone in the treatment of depressed outpatients.
J Clin Psychiatry
1995
56
30
6
PubMed
PubMed
Olie
JP
,
Gunn
KP
,
Katz
E
.
A double-blind placebo-controlled multicentre study of sertraline in the acute and continuation treatment of major depression.
Eur Psychiatry
1997
12
34
41
CrossRef

PubMed
Reimherr
FW
,
Chouinard
G
,
Cohn
CK
,
Cole
JO
,
Itil
TM
,
LaPierre
YD
.
Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.
J Clin Psychiatry
1990
51
18
27
PubMed
PubMed
Reimherr
FW
,
Byerley
WF
,
Ward
MF
,
Lebegue
BJ
,
Wender
PH
.
Sertraline, a selective inhibitor of serotonin uptake, for the treatment of outpatients with major depressive disorder.
Psychopharmacol Bull
1988
24
200
5
PubMed
PubMed
Rickels
K
,
Amsterdam
J
,
Clary
C
,
Fox
I
,
Schweizer
E
,
Weise
C
.
A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients.
Acta Psychiatr Scand Suppl
1989
350
117
23
PubMed
CrossRef

PubMed
Shrivastava
RK
,
Shrivastava
SH
,
Overweg
N
,
Blumhardt
CL
.
A double-blind comparison of paroxetine, imipramine, and placebo in major depression.
J Clin Psychiatry
1992
53
48
51
PubMed
PubMed
Thase
ME
.
Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group.
J Clin Psychiatry
1997
58
393
8
PubMed
CrossRef

PubMed
Heiligenstein
JH
,
Ware
JE
Jr
,
Beusterien
KM
,
Roback
PJ
,
Andrejasich
C
,
Tollefson
GD
.
Acute effects of fluoxetine versus placebo on functional health and well-being in late-life depression.
Int Psychogeriatr
1995
7
125
37
PubMed
CrossRef

PubMed
Trivedi
MH
,
Pigotti
TA
,
Perera
P
,
Dillingham
KE
,
Carfagno
ML
,
Pitts
CD
.
Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder.
J Clin Psychiatry
2004
65
1356
64
PubMed
CrossRef

PubMed
Wade
A
,
Michael Lemming
O
,
Bang Hedegaard
K
.
Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care.
Int Clin Psychopharmacol
2002
17
95
102
PubMed
CrossRef

PubMed
Walczak
DD
,
Apter
JT
,
Halikas
JA
,
Borison
RL
,
Carman
JS
,
Post
GL
.
The oral dose-effect relationship for fluvoxamine: a fixed-dose comparison against placebo in depressed outpatients.
Ann Clin Psychiatry
1996
8
139
51
PubMed
CrossRef

PubMed

Figure 1.

Study flow diagram.

The number of included articles differs from the number of included studies because some studies have multiple publications.

Figure 2.

Relative benefit of response comparing selective serotonin reuptake inhibitors (SSRIs) with other SSRIs

All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

* Based on meta-analysis of head-to-head trials.

Based on indirect comparisons with meta-regression.

Figure 3.

All estimates are based on network meta-analyses except for those marked with an asterisk or a dagger.

* Based on meta-analysis of head-to-head trials.

Based on indirect comparisons with meta-regression.

Figure 4.

All estimates are based on network meta-analyses except for those marked with an asterisk.* Based on meta-analysis of head-to-head trials.

Table 1. Second-Generation Antidepressants Approved for Use in the United States

Appendix Table 1. Characteristics of Studies with Poor Internal Validity

Appendix Table 2. Comparative Efficacy and Effectiveness Studies on Therapy for Major Depressive Disorder

Appendix Table 3. Comparative Efficacy and Effectiveness Studies on Therapy for Dysthymia

Appendix Table 4. Comparative Efficacy and Effectiveness Studies on Therapy for Subsyndromal Depressive Disorders

Appendix Table 5. Comparative Efficacy and Effectiveness Studies on Maintaining Remission and Preventing Relapse

Appendix Table 6. Comparative Efficacy and Effectiveness Studies on Therapy for Recurrent and Treatment-Resistant Depression

Appendix Table 7. Placebo-Controlled Studies of Relapse and Recurrence

Appendix Table 8. Comparative Efficacy and Effectiveness Studies of Treatment in Adults with Major Depressive Disorder and Accompanying Symptoms

Appendix Table 9. Studies of Comparative Risk for Harms in Adults with Major Depressive Disorder

Appendix Table 10. Comparative Efficacy and Effectiveness Studies in Subgroups

Appendix Table 11. Randomized, Placebo-Controlled Trials Included for Indirect Comparisons

Table 2. Summary of Findings on General Effectiveness

Table 3. Summary of Findings on Adverse Events: Comparative Risk for Harms

Table 4. Summary of Findings on Effectiveness in Subgroups

Table 5. Main Differences in Specific Adverse Events

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1 Comment

Thomas E. Finucane

Johns Hopkins School of Medicine

December 5, 2008

Comparative Benefits and Harms of Second-Generation Antidepressants

Dr. Gartlehner and colleague's Background Paper on the comparative benefits and harms of second-generation antidepressants (SGAs) finds "no substantial differences in efficacy among these drugs," but notes that "other differences" may be relevant in choosing a drug (1). They also note that 69% of the studies were supported by the pharmaceutical industry, and for 21% of the studies, source of funding could not be determined. Drug company funding has a strong impact on the published literature. Companies naturally tend to seek publication of results favorable to their products (2).

Seven fair quality studies are cited, all showing that mirtazapine leads to higher weight gain than other SGAs; not shown is that all seven studies are sponsored by mirtazapine's vendor, Organon, and that three of the seven have at least one author who is a drug company employee. Without any good evidence, a market niche for mirtazapine has been created: depressed patients who are losing weight.

Writers of systematic reviews must decide how to weigh vendor-sponsored evidence, especially when most or all of the available evidence is vendor-sponsored. Here is a modest suggestion. In bibliographies, why not make the first initial of the first author scarlet if the paper is sponsored by the vendor? This would make it easy to see where the influence of industry might be suspected.

References

1. Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, et al. Comparative benefits and harms of second-generation antidepressants: Background paper for the American College of Physicians. Ann Intern Med. 2008; 149: 734-750.

2. Rising K, Bacchetti P, Bero L. Reporting bias in drug trials submitted to the Food and Drug Administration: A review of publication and presentation. PLoS Med 2008; 5(11): e217: 0001-10.

Conflict of Interest:

None declared

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2008 American College of Physicians

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