Can GLP-1 Drugs Help with Depression, Addiction, and Other Psychiatric Conditions? A Systematic Review | Research

The takeaway

GLP-1 receptor agonists showed mixed effects on psychiatric symptoms across 26 studies — some benefits for depression, cocaine craving, and alcohol use, but overall results remain inconclusive and require further research.

3 of 9 RCTs showed significant effects
Only a third of randomized controlled trials found statistically significant psychiatric benefits from GLP-1 receptor agonists, highlighting that despite promising signals, the evidence remains inconclusive.

What the researchers found

Among 26 studies (n=3,020), 5 evaluated psychiatric symptoms as primary outcomes and 21 as secondary outcomes:

Primary psychiatric outcomes: Exenatide 2 mg weekly reduced cocaine craving in a case series but showed no significant change in a separate study (n=12, p=0.46). Dulaglutide 1.5 mg weekly did not significantly affect smoking cessation (RR=0.87, p=0.25) but reduced alcohol consumption by 29% in a secondary analysis.

Secondary psychiatric outcomes: Liraglutide 1.8 mg/day significantly improved depression and anhedonia. Semaglutide improved diabetes-related quality of life and anxiety (Cohen's d=0.48) compared to dulaglutide. Exenatide showed mixed results, with one RCT finding significant BDI score reduction (Δ=-5.2).

Overall: Only 3 of 9 included RCTs reported significant effects on primary psychiatric outcomes; 6 reported null findings.

Why it matters

Millions of people now take GLP-1 drugs, and there is enormous public interest in their potential psychiatric benefits — especially for addiction and depression. This systematic review provides the most comprehensive assessment to date, tempering the hype with evidence. While some signals are promising, the mixed results highlight that GLP-1 drugs are not yet proven psychiatric treatments and more rigorous research is needed.

How the study worked

Systematic review searching OVID databases from inception to November 2024. 26 studies (n=3,020) were included, categorized by whether psychiatric outcomes were primary or secondary. 10 registered clinical trials were also identified. Risk of bias for the 9 included RCTs was assessed using the JBI Critical Appraisal Checklist, with all meeting majority of criteria indicating moderate-to-high methodological quality.

What this study cannot tell us

The included studies were heterogeneous in design, GLP-1RA type, dosing, psychiatric outcomes measured, and patient populations. Most psychiatric outcomes were assessed as secondary endpoints, not primary. The number of studies with primary psychiatric outcomes was very small (5). Case series and observational studies constitute much of the evidence. Publication bias may favor positive findings. The review could not perform meta-analysis due to study heterogeneity.

How to read the evidence

This is a well-conducted systematic review of heterogeneous studies. While the review methodology is strong, the underlying evidence is mixed — comprising case series, observational studies, and RCTs with variable quality. The inconsistent findings across studies limit the overall evidence strength for psychiatric applications.

When this study was published

Published in 2025 with literature search through November 2024, this is the most current systematic review of GLP-1RA psychiatric effects and identifies 10 ongoing clinical trials that may provide clearer answers.

The bigger picture

The potential psychiatric effects of GLP-1 receptor agonists are among the most discussed topics in current medicine. Anecdotal reports of reduced addictive behaviors have generated enormous interest. This systematic review provides important context: while the biological rationale is strong (GLP-1 receptors exist in brain reward centers), the clinical evidence is still emerging and inconsistent. The 10 registered clinical trials identified suggest the field is actively working to resolve these questions.

Questions still open

Will dedicated, adequately powered RCTs for specific psychiatric conditions (depression, addiction) show clearer benefits?
Do different GLP-1RAs have different psychiatric profiles based on their brain penetration?
Are the psychiatric benefits of GLP-1RAs independent of weight loss, or mediated entirely through metabolic improvements?

Common questions

Can GLP-1 drugs like semaglutide help with depression or addiction?

The evidence is mixed. Some studies showed benefits — liraglutide improved depression, exenatide reduced cocaine craving, and dulaglutide reduced alcohol consumption. But many other studies found no significant effects, and only 3 of 9 randomized trials showed positive psychiatric outcomes. It's too early to recommend GLP-1 drugs specifically for psychiatric conditions.

Why might GLP-1 drugs affect mental health?

GLP-1 receptors are found in brain areas involved in reward, mood, and motivation. This provides a biological basis for potential psychiatric effects. Some researchers think GLP-1 drugs might reduce addictive behaviors by dampening reward signaling, while anti-inflammatory effects could improve depression. However, these mechanisms are still being studied and clinical evidence remains inconclusive.

Read the original research

Efficacy and Safety of Glucagon-Like Peptide-1 Agonists for Psychiatric Symptoms: A Systematic Review.

Brain and behavior, 15(7), e70661

View on PubMed ↗Publisher’s paper ↗

Citation

Meshkat, Shakila; Di Luciano, Corinna; Swiderski, Alyssa; Li, Gloria; Aguilar, Reinhard Janssen; Dunkley, Benjamin T; Reichelt, Amy C; Zhang, Yanbo; Greenshaw, Andrew; Vermetten, Eric; Jetly, Rakesh; Dash, Satya; Agarwal, Sri Mahavir; Swainson, Jennifer; Bhat, Venkat. (2025). Efficacy and Safety of Glucagon-Like Peptide-1 Agonists for Psychiatric Symptoms: A Systematic Review.. Brain and behavior, 15(7), e70661. https://doi.org/10.1002/brb3.70661