Background: Treatment strategies for acute neuroleptic-induced akathisia (NIA) contain anticholinergic (antimuscarinic) agents, dopamine agonists, γ-aminobutyric acid (GABA)-ergic agents, β-blockers, benzodiazepines, and serotonin antagonists. Nevertheless, many patients who suffer from acute akathisia fail to respond to treatment. In earlier studies, vitamin B 6 was found to be effective in the treatment of neuroleptic-induced movement disorders. The purpose of this study was to evaluate the efficacy of vitamin B 6 in the treatment of acute NIA. This is the first report of B 6 as a treatment for NIA. Method: This study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design. The Barnes Akathisia Scale (BAS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale (CGI) were used to assess the severity of NIA and psychotic symptoms. The BAS assessment was made at baseline and every day during the study. The BPRS and CGI were completed at baseline and at the end of the study. Results: The vitamin B 6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B 6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B 6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037). Conclusion: Our preliminary results indicate that high doses of vitamin B 6 may be useful additions to the available treatments for NIA, perhaps due to its combined effects on various neurotransmitter systems.