Anhedonia and neuropsychotropics: A pharmacovigilance-pharmacodynamic study

Anhedonia is defined as inability to experience pleasure or enjoyment from activities normally pleasurable. Role of drugs in occurrence of anhedonia is little known. The study was performed to investigate, first associations between anhedonia and exposure to neuropsychotropics and, second potential pharmacodynamic mechanisms of this adverse drug reaction.

The first part of the study used individual case safety reports (ICSRs) in adults registered in the global pharmacovigilance database, Vigibase®, between 01/01/2000 and 31/12/2024 with neuropsychotropics. Results are shown as reporting odds ratios (ROR) with their 95%CI. Second, we performed a pharmacovigilance-pharmacodynamic study using linear regression analyses to explore the association between anhedonia with antidepressants and binding affinities for their monoamine transporters.

Among 24,913,179 ICSRs, 1123 reported anhedonia with neuropsychotropics, mainly in females (52.5%) and between 18-44 years (55.6%). Significant associations were found with psycholeptics [ROR=1.23 (1.14-1.33), including second generation of antipsychotics and anxiolytics], psychoanaleptics [ROR=1.66 (1.52-1.82), including serotonin reuptake inhibitors and venlafaxine but not other antidepressants] and some other drugs like naltrexone, varenicline, duloxetine, clonazepam or oxycodone. No association was found for anesthetics, other analgesics, other antiepileptics, hypnotics/sedatives, or antiparkinsonians. Direct drug comparisons found significant ROR values for psychoanaleptics versus psycholeptics [1.35 (1.20-1.51)], for antidepressants versus antipsychotics [2.63 (2.24-3.09)] and for antidepressants versus anxiolytics [1.27 (1.11-1.45)]. No significant association was found between monoamine pKi values and occurrence of anhedonia with antidepressants.

Among neuropsychotropics, serotonin reuptake inhibitors, benzodiazepine anxiolytics and antipsychotics are associated with anhedonia reports. We were unable to find any correlation between anhedonia reports with antidepressants and their direct effects on monoamine transporters.