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“It's been 3 weeks on semaglutide,” wrote an anonymous user on the Quora website last year. “I feel completely numb and depressed ... does this side effect go away?” “I feel like I cannot feel joy from anything anymore. No energy. No motivation,” wrote another semaglutide user on Reddit. As use of glucagon-like peptide-1 (GLP-1)–receptor agonists has soared worldwide, anecdotal accounts of drug-associated dysphoria and depression have created new clinical and regulatory concerns.
As an expert outlines in a March 2024 review (Expert Opin Drug Saf 2024 Mar 26; [e-pub]), so far no convincing evidence supports a clear cause-and-effect relationship. Premarketing studies of the drugs showed no mental health sequelae; subsequent analyses of real-wo…