What are the effects of fluoxetine treatment in overweight or obese adults?
Fluoxetine – Is a drug used to treat depression, the side effect of which is decreased appetite. Therefore, it is suspected that fluoxetine may be used as a treatment for people who are overweight or obese. For this group of people, fluoxetine is a non-labeled medication, which means it is not licensed to treat obesity.
Study characteristics. We found 19 randomized controlled trials (clinical trials in which people are randomly assigned to one of two or more treatment groups) that mainly evaluated women who received different doses of fluoxetine. A total of 1,280 participants who were overweight or obese received fluoxetine, and 936 participants received mostly a placebo or other anti-obesity medication. Participants in the included studies were followed for a period of three weeks to one year.
Main findings In the main comparison group (fluoxetine versus placebo) and at all doses of fluoxetine, there was a weight loss of 2.7 kg in favor of fluoxetine. However, it is unclear whether further research will show a positive effect of fluoxetine. Side effects were observed in 399 of 627 participants (63.6%) who received fluoxetine, compared with 352 of 626 participants (56.2%) who received placebo. Dizziness, drowsiness, fatigue, insomnia, and nausea were observed about twice as often in patients after taking fluoxetine compared with placebo. A total of 15 of 197 participants (7.6%) who received fluoxetine, compared with 12 of 196 participants (6.1%) who received placebo, experienced depression. Studies did not report any cause of death, health-related quality of life, or socioeconomic outcomes.
Data are current as of December 2018.
Certainty of evidence. The overall reliability of the evidence was low or very low, mainly because of the small number of studies for each outcome measure and the small number of participants.
Low confidence data suggest that although fluoxetine is not approved for use in this indication, it may reduce weight compared to placebo. However, low confidence data indicate an increased risk of dizziness, drowsiness, fatigue, insomnia, and nausea after treatment with fluoxetine.
Fluoxetine is a serotonin reuptake inhibitor indicated for the treatment of major depression. It is also thought to affect weight control: this occurs through changes in appetite, resulting in decreased food intake and normalization of unusual eating behavior. However, the risk-benefit ratio of off-label use of this medication for this indication remains unclear.
Evaluation of the effects of fluoxetine in adults who are overweight or obese.
We searched the Cochrane Library, MEDLINE, Embase, LILACS, ICTRP search portal, and ClinicalTrials.gov, and on the World Health Organization’s (WHO) ICTRP search portal. The last search date in all databases was December 2018, no language restrictions applied.
Randomized controlled trials (RCTs) comparing fluoxetine with placebo, other anti-obesity agents, non-pharmacological treatment, or no treatment in overweight or obese adults without depression, mental illness, or abnormal eating patterns were included.
Two reviewers independently verified the relevance of abstracts and titles. One author screened for inclusion, data extraction, and risk of bias, and a second author screened for bias. Overall reliability of the studies’ evidence was assessed using GRADE criteria. We contacted the study authors by e-mail for more information. We performed a meta-analysis with random effects and calculated hazard ratios (HRs) with 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes.
1,036 records were found, 52 full-text articles were reviewed, and 19 completed RCTs were included (one study is awaiting evaluation). The studies included 2,216 participants, 1,280 were randomized to receive fluoxetine (60 mg/day, 40 mg/day, 20 mg/day, and 10 mg/day), and 936 participants were randomized to various comparison groups (placebo; antiobesity drugs diethylpropion, fenproporex, mazindol, sibutramine, metformin, fenfluramine, dexfenfluramine, fluvoxamine, 5-hydroxytryptophan; no treatment and omega-3 gel). Nineteen RCTs had 56 studies. Fifteen studies were parallel RCTs and four were cross-sectional RCTs. Participants in the included studies were followed for a period of three weeks to one year. The reliability of the evidence was low or very low: most studies had a high risk of bias in one or more areas of risk of bias.
In the main comparison group (fluoxetine vs. placebo) and at all doses of fluoxetine and duration of treatment, MD was -2.7 kg (95% CI -4 to -1.4, P < 0.001; 10 studies, 95 participants; low confidence evidence) < 0.001; 10 studies, 956 participants; low confidence). 95% prediction interval ranged from -7.1 kg to 1.7 kg. MD in body mass index (BMI) reduction with all doses of fluoxetine compared to placebo was -1.1 kg/m² (95% CI -3.7-1.4; three studies, 97 participants; very low confidence). Only nine placebo-controlled studies reported adverse events. Adverse events occurred in 399 of 627 participants (63.6%) receiving fluoxetine, compared with 352 of 626 participants (56.2%) receiving placebo. Meta-analysis of random effects showed an increased risk of at least one adverse event of any type in the fluoxetine groups compared with placebo (OR 1.18, 95% CI 0.99-1.42, p=0.07; nine studies, 1253 participants; low confidence). 95% prediction interval ranged from 0.74 to 1.88. After treatment with fluoxetine, adverse events in the form of dizziness, drowsiness, fatigue, insomnia, and nausea were observed about twice as often compared to placebo. A total of 15 of 197 participants (7.6%) who received fluoxetine, compared to 12 of 196 participants (6.1%) who received placebo, experienced depression. The OR for all doses of fluoxetine compared with placebo was 1.20 (95% CI 0.57 to 2.52, p=0.62, three studies, 393 participants, very low confidence). All-cause mortality, health-related quality of life, and socioeconomic outcomes were not reported.
Comparisons of fluoxetine with other anti-obesity drugs (three studies, 234 participants), omega-3 gel (one study, 48 participants), and no treatment (one study, 60 participants) showed inconclusive results (very low confidence).