[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.
| Antidepressant | Quality of Evidence for the drug | Quantitative Weight Change in kg. >12 weeks unless indicated |
|---|---|---|
| Weight gain | ||
| Paroxetine | 1 | 2.73 CI 0.78 to 4.68 * |
| Mirtazapine | 1 | 2.59 CI -0.23 to 5.41 * |
| Doxepine | 2 | 2.73 |
| Amitriptyline | 1 | 2.24 CI 1.82 to 2.66 |
| Citalopram | 1 | 1.69 CI -0.97 to 4.34 |
| Nortriptyline | 1 | 1.24 CI -0.51 to 2.99 |
| Clomipramine | 3 | 1.0 CI -0.44 to 2.43 ≤ 12 weeks |
| Desipramine | 3 | 0.82 CI -0.77 to 2.42 ≤ 12 weeks |
| Imipramine | 1 | -0.04 CI -1.36 to 1.28 * |
| Duloxetine | 1 | 0.71 CI -0.23 to 1.65 |
| Escitalopram | 1 | 0.65 CI -0.16 to 1.45 |
| Trimipramine | 3 | Qualitative data only |
| Minimal Effect on weight | ||
| Venlafaxine | 3 | 0.5 CI 0.74 to -0.27 ≤ 12 weeks |
| Fluvoxamine | 3 | -0.02 CI -0.49 to 0.45 ≤ 12 weeks |
| Fluvoxamine CR | 1 | Qualitative data only |
| Sertraline | 1 | -0.12 CI -1.65 to 1.42 ≤ 12 weeks |
| Trazodone | 3 | -0.2 CI -0.94 to 0.54 ≤ 12 weeks |
| Moclobemide | 3 | -0.21 CI -0.30 to -0.13 ≤ 12 weeks |
| Fluoxetine | 1 | -0.31 CI -1.04 to 0.43 |
| Desvenlafaxine | 2 | -0.8 kg, Minimal effect on weight in both short/term and long term use( 12 weeks) |
| Weight loss | ||
| Bupropion | 1 | -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
| MAOI | Quality of Evidence for the Drug | Effect on Weight |
|---|---|---|
| Phenelzine | 3 | Qualitative gain only |
| Isocarboxazide | 3 | Qualitative gain only |
| Tranylcypromine | 3 | Significant 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
- Dent, Robert, et al. “Changes in body weight and psychotropic drugs: a systematic synthesis of the literature.” PloS one 7.6 (2012): e36889.
- Serretti A, Mandelli L (2010) Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 71: 1259–1272.
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- 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
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