The 5-HT1D receptor agonist zolmitriptan for neuroleptic-induced akathisia: An open label preliminary study

Ruth Gross-Isseroff*, Ayelet Magen, Roni Shiloh, Haggai Hermesh, Abraham Weizman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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-HT 1D 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 S-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 ≥ 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.

Original languageEnglish
Pages (from-to)23-25
Number of pages3
JournalInternational Clinical Psychopharmacology
Issue number1
StatePublished - Jan 2005


  • Neuroleptic-induced akathisia
  • Zolmitriptan


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