Semaglutide Does Not Increase Depression, Suicidal Ideation in Patients With Obesity
Taking once-weekly subcutaneous semaglutide does not increase depression symptoms or suicidal ideation in patients with obesity.
Patients with overweight or obesity who take subcutaneous semaglutide 2.4 mg once a week do not have increased depressive symptoms or suicidal ideation, according to results of a post hoc analysis published in JAMA Internal Medicine.1
Semaglutide Does Not Increase Depression, Suicidal Ideation in Patients with Obesity / Kassandra - stock.adobe.com
The researchers actually found a small but not clinically significant reduction in depression symptoms among those taking semaglutide compared with those taking placebo.
Since obesity is known to be associated with several psychosocial complications, psychiatric safety should always be considered when treating patients with the condition. In the study, the researchers wanted to evaluate the psychiatric safety of once-weekly subcutaneous semaglutide in adult patients with overweight or obesity who did not have previous major psychopathology.
The post hoc analysis included pooled data from the randomized, double-blind, placebo-controlled multicenter phase 3a Semaglutide Treatment Effect in People With Obesity (STEP) 1, 2, and 3 trials as well as the phase 3b STEP 5 trial, which enrolled adults with overweight or obesity. The STEP 2 trial participants also had type 2 diabetes. Participants in all trials were randomized to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo. For this analysis, the researchers excluded those randomized to semaglutide 1.0 mg.
READ MORE: Obesity in Adolescents: Prevalence, Health Effects, and Treatment Options
The researchers used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms and the Columbia-Suicide Severity Rating Scale (C-SSRS) to assess suicidal ideation/behavior. The PHQ-9 and C-SSRS were administered at baseline and at weeks 12, 20, 36, 52, and 68 in STEP 1, 2, and 3, and again at weeks 84 and 104 in STEP 5. They also investigated psychiatric and nervous system disorder adverse events.
The analysis included 3377 participants from the STEP 1, 2, and 3 trials; they had a mean age of 49 years, and 69.6% were women. They included an additional 304 participants from the STEP 5 trial with a mean age of 47; 77.6% were women. Among the STEP 1, 2, and 3 participants, the mean baseline PHQ-9 scores were 2.0 in the semaglutide 2.4 mg group compared with 1.8 in the placebo group; both indicated no/minimal symptoms of depression. At week 68, mean PHQ-9 scores were 2.0 in the semaglutide group compared with 2.4 for placebo. This indicated that participants taking semaglutide were less likely to shift to a more severe category of PHQ-9 depression score compared with placebo (odds ratio 0.63).
Using the C-SSRS, the researchers found that less than 1% of participants reported suicidal ideation/behavior during the study period. They did not find any significant differences between participants in the semaglutide or placebo groups.
Reports of psychiatric adverse events were similar between the semaglutide and placebo groups across all trials. The researchers found that the semaglutide groups had a slightly higher incidence of nervous system disorder adverse events compared with placebo, driven largely by an increase in reports of headaches and dizziness.
Although the researchers did not find increased depressive symptoms or suicidal ideation in patients with obesity taking semaglutide, they still encourage clinicians to monitor the mental health of all patients with overweight or obesity. “This is essential for ensuring that these individuals obtain the psychiatric care they require to manage anxiety, depression, and related psychiatric complications, which may occur in the presence or absence of weight management interventions,” the researchers wrote.
READ MORE: Obesity Management Resource Center
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