Can dextromethorphan-bupropion reduce mental pain in depressed individuals? A generating hypothesis overview perspective.
Annals of general psychiatry March 17, 2025 Maurizio Pompili, Isabella Berardelli, Denise Erbuto et al.
Major depressive disorder (MDD) is a leading cause of disability globally, with prevalence twice as high in women as in men. Mental pain, distinct from depression, is a crucial framework in MDD that may precipitate suicide risk. According to Panksepp's emotional theory, the opioid system influences feelings tied to grief and separation, making it a renewed target for antidepressant treatment. Antidepressants with partial mu-opioid receptor agonism and kappa-opioid receptor antagonism could address unmet needs. The combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment for adults with MDD. It is hypothesized that this combination reduces mental pain by targeting the opioid system, potentially improving treatment outcomes.