AIM: To assess whether there is a beneficial or detrimental effect of weight reduction on mental health.
MATERIALS AND METHODS: Meta-analysis of randomized trials performed for weight loss, in which weight loss at endpoint was greater than 5% in the intervention arm and smaller than 5% in the control arm, obtained with any surgical, endoscopic, or EMA-approved pharmacological intervention. The endpoints were the incidence of overall and specific psychiatric adverse events.
RESULTS: Weight loss was associated with a reduced risk of major depression (MH-OR 0.45 95% CI [0.21, 0.94], I2 = 0), and overall depression (MH-OR 0.72 [0.54, 0.97]); in subgroup analyses, a weight loss greater than 10% was associated with a lower incidence of depression than smaller weight loss (p = 0.04), whereas no difference was found between different interventions. No difference was detected in the incidence of anxiety (MH-OR 1.04 [0.78, 1.39]), of serious (M-H, OR CI 1.07 [0.78, 1.47]) and overall (MH-OR 1.09 [0.89, 1.34]) psychiatric adverse events, suicidal ideation (M-H, OR 0.87 [0.44, 1.70]), or suicide (M-H, OR 0.87 [0.44, 1.70]). An improvement in functional health status was detected, either as SF-36 Mental (SMD-IV 0.45 [0.37, 0.52]) or SF-36 Physical function (SMD-IV 0.29 [0.14, 0.44]) or IWQOL Lite Physical function (MD-IV 3.96 [1.60, 6.32]).
CONCLUSION: Weight-reducing treatments were associated with a beneficial effect on quality of life and functional health status and a reduced risk of depression, without any safety signal for serious or non-serious psychiatric adverse events.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
This meta-analysis provides reassuring evidence that modern weight-reducing interventions improve both mood and functional quality of life without increasing psychiatric risk. The observed reduction in depression, particularly with greater weight loss, highlights the broader mental health benefits of effective obesity treatment. These data help clinicians address concerns about the psychological safety of GLP-1–based therapies and support integrating weight management into comprehensive mental and metabolic care.
Physician rater
This meta-analysis clearly shows how medical interventions for weight loss can improve psychological well-being. Nevertheless, I have my doubts about the results of this study: 1. All authors have conflicts of interest in connection with manufacturers of weight loss drugs; 2. All the different interventions (Y-Roux bypass, Orlistat, Topiramate, Tirzepatide, etc) are lumped together; 3. It is clear that severe psychiatric events are increasing in frequency, albeit not significantly, but numerically very clearly; and 4. There is no indication of how those affected fare when their weight increases again after the end of the intervention, which is not observed in the included RCTs. In this respect, I am certain that the last word on this matter has not yet been spoken.
Physician rater
As a geriatric psychiatrist, we're well aware of the positive effects of lifestyle interventions like diet and exercise on mood and mental health wellbeing. However, this article adds to that evidence base by showing an additional effect of weight loss in reducing depression risk that has a moderate effect size that is larger than I would have predicted. After learning about the results of this study, I would be more likely to encourage and track weight loss as a means of potentially improving mood in overweight and obese patients with depression.
Physician rater
Useful conclusions especially as more practitioners in primary care clinics are prescribing weight-loss medications.
, McMaster University