Fluoxetine: can it decrease weight in obese and overweight patients?

This evidence summary presents the best available evidence on the effectiveness of fluoxetine in decreasing weight.

Introduction

Selective serotonin reuptake inhibitors (SSRIs) are associated with weight changes. Fluoxetine has been used for depression, obsessive compulsive disorders, panic disorders and bulimia; an association with weight loss has also been found by doctors.^2,3

It works by inhibiting presynaptic reuptake of serotonin. Blocking serotonin reuptake results in decreased food intake, changes in food selection, normalisation of unusual eating behaviours and decreasing frequency of binge eating.⁴ Fluoxetine was shown in small studies to decrease food intake in both normal and obese patients but there are no systematic reviews that summarise the evidence on this topic. The current evidence summary will present the effectiveness of fluoxetine to decrease weight in obese and overweight patients.^4,5

Characteristics of the study

The review included 19 randomised controlled trials where participants received fluoxetine, placebo or another anti-obesity medicine. Overweight (BMI of 25–29.9) and obese (BMI of 30 and over) participants were included in the review.

Quality of the studies

There was low to very low quality evidence to suggest that fluoxetine may decrease weight compared to placebo. Limitations to the systematic review include risk of bias, low number of trials and participants, and consistent confidence intervals for benefits and harms.

Results

• For the Cochrane systematic review, the following databases were searched; Cochrane Library, MEDLINE, Embase, LILACS, the ICTRP Search Portal and ClinicalTrials.gov and World Health Organization.
• (WHO) ICTRP Search Portal until December 2018.
• The primary outcomes measures were; weight loss (kg), health-related quality of life and adverse events.
• The review included a total of 19 studies with 2,216 participants. The studies included various interventions and comparators. The interventions included a range of fluoxetine doses varying between 10 and 60 mg per day. The comparators group included one of the following; placebo, anti-obesity medications such as sibutramine, metformin, fenfluramine, dexfenfluramine, fluvoxamine, 5-hydroxy-tryptophan; no treatment; and omega-3 gel. The participants were followed up for a period of between three weeks to up to one year.
• Secondary outcomes measures were; anthropometric measurements other than weight loss in kg such as body mass index (BMI), morbidity, all-cause mortality and socioeconomic effects.
• A total of seven studies (819 participants) compared fluoxetine 60 mg with placebo. There was a significant difference in weight loss between the fluoxetine and placebo group (MD = −2.5 kg; 95% CI −3.8 to −1.2; P < 0.001).
• A total of two studies (182 participants) compared fluoxetine 40 mg with placebo. There was no significant difference in weight loss between fluoxetine and placebo group (MD = −4 kg; 95% CI −8.8 to 0.8; P = 0.10).
• A total of three studies (279 participants) compared fluoxetine 20 mg with placebo. There was no significant difference in weight loss between the fluoxetine and placebo group (MD = −1.5 kg; 95% CI −3.5 to 0.5; P = 0.15).
• There was a significant increase in the risk of at least one adverse event in the fluoxetine 60 mg/d group compared with the no-treatment group (RR =8.67; 95% CI 2.94 to 25.59; P < 0.001).
• There was no significant difference in the rate of discontinuation of fluoxetine due to adverse events compared to placebo (RR = 1.88; 95% CI 0.87 to 4.06; P = 0.11; 8 trials).
• Regarding BMI, three trials compared fluoxetine with placebo. There was a non-significant reduction in BMI across all fluoxetine doses compared with placebo. MD = −1.1 kg; 95% CI −3.7 to 1.4; P = 0.10).
• None of the trials reported any measures on quality of life, all-cause mortality and socioeconomic effects.
• Three studies compared different doses of fluoxetine versus six different anti-obesity medicines and found no significant difference in weight loss for fluoxetine compared with sibutramine and metformin. However, fluoxetine showed greater benefit in weight loss than diethylpropion.

Conclusion

Low quality evidence suggests that fluoxetine 60 mg, compared to placebo, decreased weight by 2.5 kg with a 95% confidence interval of 1.4 kg and 6.4 kg. However, adverse effects were seen almost twice as frequently in those on active treatment. There were inconclusive results when comparisons were made between fluoxetine, other anti-obesity drugs and no treatment.

Implications for research and practice

Fluoxetine is currently used to manage depression. When it is given as an off- label medication to reduce weight, it has modest benefit in high doses. However, further research, with larger samples and more robust studies, is needed to confirm these results.

References

1. Serralde-Zúñiga AE, Gonzalez Garay AG, Rodríguez-Carmona Y, et al. Fluoxetine for adults who are overweight or obese. Cochrane Database of Systematic Reviews 2019, Issue 10. At: www.ncbi.nlm.nih.gov/pubmed/31613390
2. Maina G, Albert U, Salvi V, et al. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry 2004;65:1365–71. At : www.ncbi.nlm.nih.gov/pubmed/15491240
3. Ye Z, Chen L, Yang Z, Li Q, et al. Metabolic effects of fluoxetine in adults with type 2 diabetes mellitus: a meta-analysis of randomised placebo-controlled trials. PloS One 2011;6(7):e21551. At: www.ncbi.nlm.nih.gov/pubmed/21829436
4. Orzack M, Friedman L, Marby D. Weight changes on fluoxetine as a function of baseline weight in depressed outpatients. Psychopharmacol Bull 1990;26:327–30. At: www.ncbi.nlm.nih.gov/pubmed/2274632
5. Harto N, Spera K, Branconnier R. Fluoxetine-induced reduction of body mass in patients with major depressive disorder. Psychopharmacol Bull 1988;24:220–3. At: www.ncbi.nlm.nih.gov/pubmed/3264922