Lack of efficacy of the 5-HT3 receptor antagonist granisetron in the treatment of acute neuroleptic-induced akathisia

The specific mechanism underlying the apparent involvement of the serotonergic (5-HT) system in the pathophysiology of extrapyramidal side-effects, particularly neuroleptic-induced akathisia (NIA), remains unknown. We hypothesized that the 5-HT3 receptor subtype may play a role in the light of the moderate-to-high affinity to this receptor of some of the atypical antipsychotic agents which have a low propensity to cause akathisia, as well as our earlier findings with the 5-HT2/5-HT3 antagonist mianserin. In an open-label pilot study, we administered the selective 5-HT3 antagonist granisetron (fixed dose, 2 mg/day) for 4 days to 10 neuroleptic-treated patients with acute NIA Three patients discontinued granisetron because of a lack of response. The remainder showed no significant change in score on the Barnes Akathisia Scale during the trial. NIA symptoms remained unchanged or worsened in five patients (71.4%) and improved to a certain degree in only two. It seems that the 5-MT3, subtype of serotonergic receptor is not involved in the development of NIA, and 5-HT3 antagonists are ineffective in the serotonin-related pharmacotherapy of NIA. Int Clin Psychopharmacol 14:357-360 (C) 1999 Lippincott Williams and Wilkins.