Neuroleptic-induced
akathisia (NIA) is a common, sometimes incapacitating, adverse side-effect of
antipsychotic drugs (APDs). Several non-selective post-synaptic 5-HT2 blockers have shown a beneficial antiakathisic effect. We hypothesized that selective stimulation of the presynaptic 5-HT1D serotonergic inhibitory
autoreceptor could also be beneficial in NIA. The study group included eight
schizophrenia inpatients with acute or chronic NIA who were treated with unchanged doses of APDs. Participants received, in an open-labelled design, 7.5 mg/day of
zolmitriptan (selective
5-HT1D agonist) for 3 consecutive days. Positive and Negative Syndrome Scale and Barnes
akathisia scale (BAS) scores were monitored before and at the end of the study. BAS score decreased by 5.25 points following
zolmitriptan administration (9.0+/-2.27 to 3.75+/-2.55, t=6.1, d.f.=7, P=0.0005). In one case, the BAS score dropped from a 3-year score >or=9 points (while relatively non-responsive to numerous antiakathisic agents) to 4 points at endpoint. In conclusion,
zolmitriptan appears to exert significant and rapid beneficial antiakathisic effect, even in chronic and resistant NIA. Larger, long-term, double-blind, placebo- and comparator- (e.g.
propranolol) controlled studies are required to substantiate the efficacy, safety and tolerability of
zolmitriptan, as well as the role of serotonergic neurotransmission in NIA.