Two years after commencing the treatment, he exhibited an irregular sleep-wake cycle with a dominant 48-h clrcabidlan component. When therapy with haloperldol was changed to atypical neuroleptic risperidone, the timing and duration of sleep episodes became more organized, although his sleep-wake schedule still remained somewhat disturbed. Addition of melatonin as a secondary therapy fully recovered the patient’s sleep-wake clrcadian Inhibitors,research,lifescience,medical rhythm. This was accompanied by improvement

in his quality of life, social interactions, and employment status.61 These findings support the proposition that whereas atypical neuroleptics like clozapine and risperidone enhance the congruity of the individual’s sleep-wake cycle with the environment, typical neuroleptics like haloperldol and flupentixol might alter the circadlan sleep-wake rhythm. Since this effect was evident in several medical disorders, eg, schizophrenia, Alzheimer’s disease, Inhibitors,research,lifescience,medical and Tourette syndrome, it was argued that CRSDs are side effects of typical neuroleptics,

rather than an illness-related phenomenon.58-61 The exact mechanisms through which typical and atypical neu-roleptics exert their differential effects on sleep-wake cycle remain to be elucidated. Clinical evidence indicates that apart from neuroleptics other psychoactive drugs, such as specific selective serotonin inhibitors Inhibitors,research,lifescience,medical (SSRIs), can trigger the emergence of CRSDs as a side effect. Hermesh et al62 described Inhibitors,research,lifescience,medical 10 patients with obsessive-compulsive disorder who developed

DSPS during fluvoxamlne treatment. It was postulated that delayed sleep-wake schedule in this case series was iatrogenic to fluvoxamlne based on the http://www.selleckchem.com/CXCR.html following observations: (I) all patients received no other medications except fluvoxamlne prior to the onset of DSPS; (II) in all patients, DSPS first occurred following fluvoxamlne initiation; (iii) when fluvoxamlne was withdrawn or the dose considerably reduced, the sleep-wake cycle returned to normal; and (Iv) with reexposure to fluvoxamlne, DSPS recurred. Interestingly, emergence of DSPS was quite specific to fluvoxamlne; Inhibitors,research,lifescience,medical treatment with two other SSRIs (clomipramine and fluoxetine) has not been associated with any adverse effects on sleepwake cycle of these patients. The authors hypothesized that the alteration those of sleep-wake schedule or the lack of it by different SSRI agents might depend on the differentlal effects of these drugs on serum melatonin levels.62 To summarize, the above cases indicate that certain psychoactlve medications might have adverse effects on the circadlan rhythm of the sleep-wake cycle. To date, we have clinical evidence of such effects for haloperldol, flupentixol, and fluvoxamlne. Whether there are additional psychotropics associated with disruptions of the sleepwake schedule, whether the response is doseand timedependent, and what the characteristics are of the particular patients who might develop CRSDs while on these drugs, remain questions for future research.