Elsevier

Journal of Affective Disorders

Volume 180, 15 July 2015, Pages 179-184
Journal of Affective Disorders

Research report
Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials

https://doi.org/10.1016/j.jad.2015.03.021Get rights and content
Under a Creative Commons license
open access

Abstract

Background

Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method.

Methods

We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40 mg/d.

Results

We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40 mg/day was equivalent to paroxetine dosage of 34.0 mg/day, agomelatine 53.2 mg/day, amitriptyline, 122.3 mg/day, bupropion 348.5 mg/day, clomipramine 116.1 mg/day, desipramine 196.3 mg/day, dothiepin 154.8 mg/day, doxepin 140.1 mg/day, escitalopram 18.0 mg/day, fluvoxamine 143.3 mg/day, imipramine 137.2 mg/day, lofepramine 250.2 mg/day, maprotiline 118.0 mg/day, mianserin, 101.1 mg/day, mirtazapine 50.9 mg/day, moclobemide 575.2 mg/day, nefazodone 535.2 mg/day, nortriptyline 100.9 mg/day, reboxetine 11.5 mg/day, sertraline 98.5 mg/day, trazodone 401.4 mg/day, and venlafaxine 149.4 mg/day. Sensitivity analyses corroborated the results except for doxepin.

Limitations

The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants.

Conclusions

Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.

Keywords

Major depression
Antidepressive agents
Dose equivalence
Fluoxetine

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