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-HT3 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.
Poyurovsky
M
M
Research Unit, Tirat Carmel Mental Health Center, Israel.
Weizman
A
A
D000208:Acute Disease; D000328:Adult; D017109:Akathisia, Drug-Induced / Q000188:drug therapy*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D017829:Granisetron / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D017829:Granisetron; D012702:Serotonin Antagonists