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Review: venlafaxine is more effective than selective serotoninreuptake inhibitors for depression
  1. Gregory E Simon, MD, MPH
  1. Group Health Cooperative
 Seattle, WA, USA

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 QUESTION: In patients with depressive disorders, is venlafaxine more effective and tolerable than other antidepressants?

    Data sources

    Studies were identified by searching Medline, EMBASE/Excerpta Medica, BIOSIS, PsycLIT, National Research Register, HealthSTAR, SIGLE, Cochrane Database of Systematic Reviews, DARE, Cochrane Controlled Trials Register, and Current Controlled Trials. Reference lists were hand searched, and authors and study sponsors were contacted.

    Study selection

    2 reviewers independently selected randomised, double blind, controlled trials that compared venlafaxine with another antidepressant for the treatment of depression. Disagreements were resolved by discussion.

    Data extraction

    Data were extracted on patient age and sex, patient selection criteria, drug doses and regimens, quality of study methods, length of follow-up, and outcomes (depression severity, response [≥50% improvement from baseline], remission [depression rating scale score below predefined threshold], and total dropouts).

    Main results

    32 studies (5562 patients) were included. Sample sizes ranged from 28 to 382 patients (mean 179 patients). The length of follow up ranged from 4 to 48 weeks (mean 10 wks). When studies were pooled, the mean severity of depressive symptoms was lower for venlafaxine than for other antidepressants. When grouped by drug class, venlafaxine was more effective than selective serotonin reuptake inhibitors (SSRIs) but did not differ from tricyclic agents (TCAs) or other drugs. A similar treatment effect was seen for response and remission rates. Venlafaxine did not differ from other antidepressants for total dropout rates.


    In patients with depressive disorders, venlafaxine is more effective than selective serotonin reuptake inhibitors. Dropout rates do not differ between venlafaxine and other types of antidepressants.


    Clinical guidelines and systematic reviews typically hold that available antidepressants are equally efficacious and effective. The meta-analysis by Smith et al, however, found that venlafaxine led to greater reduction in depressive symptoms and greater probability of good clinical outcome than did prescription of other antidepressants in general or SSRI antidepressants in particular. Because the meta-analysis included data from traditional efficacy studies, some questions remain regarding generalisation to everyday practice.

    Firstly, did the selection process for these efficacy trials create an inadvertent bias in favour of venlafaxine? Given current medication-use patterns, previous unsuccessful treatment with SSRI drugs may have been more common than unsuccessful treatment with venlafaxine.

    Secondly, does the Hamilton Depression Rating Scale (HDRS) measure the treatment effects that matter most to patients? The authors’ point would be stronger if other measures (such as patients’ global ratings of improvement or quality of life measures) also showed an advantage for venlafaxine. The specific symptoms included in the HDRS (eg, insomnia rather than hypersomnia) might bias comparisons of venlafaxine with other classes of drugs.

    Thirdly, how might results be affected by the treatment structure of a randomised efficacy trial? Such trials typically limit dose adjustment and prohibit medication switches. Data collection ignores patients discontinuing protocol treatment. In actual practice, switching antidepressant medication is common and not an indication of treatment failure. Practicing clinicians ask, “Which medication should I try first?” rather than, “Which medication must I stick with regardless of the outcome?”

    As the authors correctly point out, their finding of an efficacy advantage for venlafaxine should be confirmed by subsequent studies, including more generalised patient populations, a broader range of outcome measures, and more typical treatment conditions. Pending such studies, this meta-analysis strengthens previous suggestions that venlafaxine offers some efficacy advantage over SSRI antidepressants.

    Venlafaxine v other antidepressants for depressive disorders at mean follow up of 10 weeks*

 QUESTION: In patients with depressive disorders, is venlafaxine more effective and tolerable than other antidepressants?

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    • Source of funding: Wyeth Laboratories.

    • For correspondence: Dr N Freemantle, University of Birmingham, Birmingham, UK. Email N.Freemantle{at}

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