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Antidepressants and Weight Change: An Evidence-Based Tool

Dent et al [1] conducted a systematic synthesis of the literature to rank the effect of psychotropic drugs on weight change. We summarize and reproduce some of their findings for antidepressant medications.

Some key points include:

  • Paroxetine and mirtazapine rank in the first two positions of drug-induced weight gain
  • Tricyclic antidepressants and MAOIs are associated with weight gain
  • Bupropion is associated with weight loss

Methods

The authors developed a hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available they went on to evaluate clinical trials that were double blind and randomly controlled, followed by cohort and other clinical trials.

Results

The ranking was based on the data from drug non naïve patients. This article presented the effect of each antidepressant on weight during two treatment periods, 4–12 weeks and ≥4 months. Data from the 4–12 week interval was used to rank the antidepressants only when data from the longer time period was not available. The quality of the evidence for the change in weight was classified as good for the ≥4 month treatment period interval. However, when the duration of the treatment period was ≤12 weeks we assigned a poor quality rating to the evidence.

AntidepressantQuality of Evidence for the drugQuantitative Weight Change in kg. >12 weeks unless indicated
Weight gain
Paroxetine12.73 CI 0.78 to 4.68 *
Mirtazapine12.59 CI -0.23 to 5.41 *
Doxepine22.73
Amitriptyline12.24 CI 1.82 to 2.66
Citalopram11.69 CI -0.97 to 4.34
Nortriptyline 11.24 CI -0.51 to 2.99
Clomipramine31.0 CI -0.44 to 2.43 ≤ 12 weeks
Desipramine30.82 CI -0.77 to 2.42 ≤ 12 weeks
Imipramine1-0.04 CI -1.36 to 1.28 *
Duloxetine10.71 CI -0.23 to 1.65
Escitalopram10.65 CI -0.16 to 1.45
Trimipramine3Qualitative data only
Minimal Effect on weight
Venlafaxine30.5 CI 0.74 to -0.27 ≤ 12 weeks
Fluvoxamine3-0.02 CI -0.49 to 0.45 ≤ 12 weeks
Fluvoxamine CR1Qualitative data only
Sertraline1-0.12 CI -1.65 to 1.42 ≤ 12 weeks
Trazodone3-0.2 CI -0.94 to 0.54 ≤ 12 weeks
Moclobemide3-0.21 CI -0.30 to -0.13 ≤ 12 weeks
Fluoxetine1-0.31 CI -1.04 to 0.43
Desvenlafaxine2-0.8 kg, Minimal effect on weight in both short/term and long term use( 12 weeks)
Weight loss
Bupropion1-1.87 CI -2.37 to -1.37

* Controversy in the ranking table.

Paroxetine and Mirtazapine

Three articles [2], [5], [6] provided controversy in the ranking between paroxetine and mirtazapine. Two articles [6] and[5] both concluded that mirtazapine caused more weight gain that paroxetine. After reviewing the evidence from the three studies, the ranking from the Serretti article was selected due to the fact that the other two studies were ranked lower on our scoring system, and were of shorter duration compared to Serretti. It was also noted that the short term data from these two articles were consistent with the short term data from Serretti. In addition, although [5] and[4] were published as two separate articles, they both obtained their data from the same references.

Tricyclic antidepressants

Based on the clinical experience of the panel, all tricyclic antidepressants are associated with some degree of weight gain. One article [3] used to rank the antidepressants provided evidence to support the claim that imipramine causes weight gain in the long term. As a result, imipramine was ranked with, but below, the other tricyclic antidepressants.

Venlafaxine

The data from Serretti on venlafaxine was ≤12 weeks. Based on the clinical experience of the panel and the lack of long term data on venlafaxine that met our selection criteria, the panel disagreed with Serretti’s classification of venlafaxine as causing weight loss. In their experience, longer term use of venlafaxine would not result in significant weight loss and as a result it was ranked just below escitalopram as venlafaxine was observed to have minimal effect on weight in the long term.

Fluoxetine

The long term data on fluoxetine from the Serretti article would imply that fluoxetine was associated with a small weight loss. The panel considered fluoxetine as having minimal effect on weight.

Although there was no data to rank four antidepressants, doxepin, trimipramine, fluvoxamine CR and desvenlafaxine, there was quantitative and/or qualitative data available and this data was included in the ranking table 4 [7]–[10].

MAO Inhibitors

MAOIQuality of Evidence for the DrugEffect on Weight
Phenelzine3Qualitative gain only
Isocarboxazide3Qualitative gain only
Tranylcypromine3Significant weight gain not noted when compared with phenelzine

There was no controversy between the two articles that ranked the MAOIs [3,4]. In the panel’s opinion, the ranking in this table was consistent with that seen in clinical practice.

References

  1. Dent, Robert, et al. “Changes in body weight and psychotropic drugs: a systematic synthesis of the literature.” PloS one 7.6 (2012): e36889.
  2. Serretti A, Mandelli L (2010) Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 71: 1259–1272.
  3. Garland EJ, Remick RA, Zis AP (1988) Weight gain with antidepressants and lithium. J Clin Psychopharmacol 8: 323–330. doi: 10.1097/00004714-198810000-00003
  4. Cantu TG, Korek JS (1988) Monoamine oxidase inhibitors and weight gain. Drug Intell Clin Pharm 22: 755–759.
  5. Gartlehner G, Thieda P, Hansen RA, Gaynes BN, Deveaugh-Geiss A, et al. (2008) Comparative risk for harms of second-generation antidepressants : a systematic review and meta-analysis. Drug Saf 31: 851–865. doi: 10.2165/00002018-200831100-00004
  6. Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, et al. (2008) Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Ann Intern Med 149: 734–750. doi: 10.7326/0003-4819-149-10-200811180-00008
  7. Feighner J, Hendrickson G, Miller L, Stern W (1986) Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. J Clin Psychopharmacol 6: 27–32. doi: 10.1097/00004714-198602000-00006
  8. Harris B, Young J, Hughes B (1986) Comparative effects of seven antidepressant regimes on appetite, weight and carbohydrate preference. Br J Psychiatry 148: 590–592. doi: 10.1192/bjp.148.5.590
  9. Davidson J, Yaryura-Tobias J, DuPont R, Stallings L, Barbato LM, et al. (2004) Fluvoxamine-controlled release formulation for the treatment of generalized social anxiety disorder. J Clin Psychopharmacol 24: 118–125. doi: 10.1097/01.jcp.0000106222.36344.96
  10. Westenberg HG, Stein DJ, Yang H, Li D, Barbato LM (2004) A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder. J Clin Psychopharmacol 24: 49–55. doi: 10.1097/01.jcp.0000104906.75206.8b

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