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Venlafaxine had higher response and remission rates than paroxetine in non-chronic treatment resistant depression
  1. Lawrence Martin, MD
  1. St Joseph's Hospital, Hamilton, Ontario, Canada

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QUESTION: In patients with non-chronic treatment resistant depression, is venlafaxine as efficacious as paroxetine in achieving treatment response and remission?


Randomised (unclear allocation concealment*), blinded (patients and clinicians)*, placebo controlled trial with 4 weeks of follow up.


Clinical centres in France.


123 patients (mean age 43 y, 72% women) with major depression (DSM-III-R) of <8 months duration. Inclusion criteria were age 18–60 years, 17-item Hamilton Depression Rating Scale (HDRS) score ≥18 and resistance (Clinical Global Impression [CGI] scale improvement score of 3 at the second treatment) to 2 antidepressant treatments for the current depression (therapeutic dose for ≥4 wk, then an alternative antidepressant at an effective dose equivalent to clomipramine 100–150 mg for ≥4 or ≥2 weeks if discontinued because of safety problems). Exclusion criteria were use of study drugs during the current episode; use of anticoagulants, phenytoin, mood stabilisers, or electroconvulsive therapy; recent use of antipsychotics or monoamine oxidase inhibitors; nonaffective disorder; suicide ideation; treatment inhibiting organic disease; seizure disorders; psychoactive substance dependence; cardiac, renal, or hepatic disease; pregnancy; or lactation. Follow up was 87% (observed case analysis).


61 patients were allocated to venlafaxine and 62 to paroxetine. Venlafaxine was started at 75 mg/day then titrated to and maintained at 200–300 mg/day by day 10 (mean dose 269 mg/d). Paroxetine was started at 20 mg/day, then increased to and maintained at 30 or 40 mg/d by day 8 (mean dose 36 mg/d).

Main outcome measures

HDRS score at day 28 for those who completed the trial. Treatment response was a HDRS score decrease >50% plus a CGI scale improvement score of 1 or 2. Remission was a HDRS score <10.

Main results

More patients who completed the trial in the venlafaxine group achieved therapeutic response (p=0.04) and remission (p=0.01) than patients in the paroxetine group (table). Using the last outcome carried forward, venlafaxine showed a trend toward achievement of response (45% v 36%, p=0.07) and had higher rates of remission (37% v 18%, p=0.02). Because of worsening scores for some patients who received venlafaxine, the groups did not differ for change in HDRS score (decrease of 11 v 10 points, p=0.6), or improvement on the CGI severity (73% v 84%, p=0.4) or improvement scale (64% v 66%, {p=0.8}). The groups did not differ for total adverse effects.

Venlafaxine v paroxetine for non-chronic treatment resistant depression


Venlafaxine was more effective than paroxetine for increasing the therapeutic response and remission rates after 4 weeks of treatment in non-chronic treatment resistant depression.


Treatment of depression has increasingly focussed on achieving full remission, because patients with residual symptoms are at substantially higher risk of relapse.1 No antidepressant has yet been shown to be consistently superior, however, in achieving remission in either new onset or resistant depression. Arguments have been made that altering both norepinephrine and serotonin levels may produce a more robust antidepressant response.2

Paroxetine is a highly specific selective serotonin reuptake inhibitor (SSRI); venlafaxine has dual noradrenergic and serotonergic activity at therapeutic doses. Previous trials of venlafaxine have suggested superior efficacy over fluoxetine in initial treatment of severe depression.3

The type of patients studied (moderately depressed, with poor response to 2 treatments) are very commonly seen in general practice and general psychiatry clinics; the study's finding, if validated, has direct relevance for day to day practice for both generalists and specialists. Uncertainty as to the trial setting (ie, primary, intermediary, or tertiary), however, will hinder clinicians' ability to compare the patients studied with their own.

The results in this study showed greater response and remission rates in the venlafaxine group. 2 problems, however, limit the robustness of the findings. Firstly, more melancholic patients and those who were severely ill were in the paroxetine group (the difference was not statistically significant). Secondly, the cut off point for declaring remission (HDRS score <10) was higher than that usually used (HDRS score ≤7 or 8).

This study is important because it further supports the strategy of using high dose venlafaxine as a preferred antidepressant in treating refractory patients.



  • Source of funding: Wyeth-Lederle, Paris, France.

  • For correspondence: Dr M F Poirier, SHU-Centre Hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris, France. Fax +33 1 45 65 81 60.

  • * See glossary.

  • p Value calculated from data in article.

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