Can dextromethorphan-bupropion reduce mental pain in depressed individuals? A generating hypothesis overview perspective.

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.

Study at a glance

Abstract

Globally, major depressive disorder, or MDD, is a leading cause of disability. It negatively impacts social interactions and significantly limits daily functioning, ultimately reducing life satisfaction. The prevalence rate is about twice as high in women as in males. It is believed that the genesis of major depressive disorder is complicated and includes biological, genetic, environmental, and psychological factors. Mental pain, although distinguishable, constitutes a crucial framework in major depressive disorder (MDD) as the pair may precipitate suicide risk. Mental pain, as conceptualized in Panksepp's emotional theory, is especially relevant when considering the key role of the opioid system, which can influence feelings tied to grief and separation. There has been a renewed interest in targeting the opioid system for antidepressant treatment in MDD and to soothe mental pain. Antidepressant drugs endowed with partial mu-opioid receptor (MOR) agonism and kappa-opioid receptor (KOR) antagonism might represent novel pharmacological tools to address unmet needs in MDD patients. The combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults affected by MDD. We hypothesized that dextromethorphan-bupropion could impact the reduction of mental pain in MDD patients by targeting the opioid system, as supported by Panksepp's theory. The combination of dextromethorphan with bupropion might deal with various aspects of mental pain, possibly improving treatment results.