BackgroundDifferent studies have suggested that antipsychotic medications of the first generation have better effectiveness for the treatment of psychotic symptoms compared with antipsychotic medications of the second generation.ObjectivesThe current study was the first pilot study in Iran that compared Haloperidol with Risperidone in the treatment of positive symptoms of psychosis among a group of methamphetamine-dependent patients.Materials and MethodsThis randomized clinical trial was designed and conducted in 2012. Overall, 44 patients who met the diagnostic and statistical manual of mental disorders, fourth edition-text revised (DSM.IV-TR) criteria for methamphetamine-associated psychosis (MAP) and were hospitalized at Razi psychiatric hospital in Tehran were selected. Patients (1: 1) were randomly divided to two groups. Overall, 22 subjects received Haloperidol (5 - 20 mg) and 22 subjects received Risperidone (2 - 8 mg). All subjects were assessed at baseline, during three consecutive weeks of treatment and one week after treatment (i.e., follow-up). Scale of assessment of positive symptoms (SAPS) was completed for each subject.ResultsThe study findings indicated that both Haloperidol (< 0.05) and Risperidone (< 0.05) were similarly applicable in the treatment of MAP but no differential effectiveness was found between the two medications. The treatment effects of both medications increased in the first two weeks of treatment and remained stable in the second two weeks.ConclusionsRisperidone and Haloperidol are two effective antipsychotic medications for the treatment of positive symptoms of MAP but other aspects of these two neuroleptic medications such as the long-term treatment effects should be studied. Further studies with more samples and longer follow-ups are suggested.