The connection of nearly all current antipsychotic drugs to their in vivo cytogenetic activity has not been yet fully investigated. Fluvoxamine, Valproic acid (VA) and Haloperidol (HLP) are three universally common consumed psychotic drugs whereas used to treat several psychiatric disorders. This study aims to investigate the cytogenetic effects of these three psychotropic drugs by evaluating the frequency of Sister Chromatid Exchanges (SCEs) and the Proliferation Rate Index (PRI) in cultured lymphocytes. Fifteen patients with psychiatric disorders (i.e. depression, bipolar and schizophrenia) consisting of smokers and non-smokers were included. Estimation of SCEs was used as a sensitive biomarker of the potential cytotoxicity, while PRI was used as a valuable marker of cytostatic activity. A significant increase of SCEs in the cultured lymphocyte of the smoker controls (P= 0.013) was found in compared to the non-smoker controls. This study found that there is no difference in the average of SCEs values in lymphocytes isolated from the smoker and non-smoker patients treated with Fluvoxamine, Valproic acid and Haloperidol (P> 0.05). A significant difference of PRI (P= 0.036) in the lymphocytes of smoker controls compared to those of the non-smoker controls were detected. This study also found a significant difference with respect to PRI between the three patient groups (P= 0.017). These results illustrated that treatment (monotherapy) of psychiatric patients with Fluvoxamine, Valproic acid, and Haloperidol exerts a significant cytostatic but not cytotoxic effect on their lymphocytes whereas these effects are intensified by smoking.