Vitamin D impact in affecting clozapine plasma exposure: A potential contribution of seasonality.

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity. In the literature, papers showed how psychiatric disorders could be associated with low vitamin D levels, but a few studies focusing on its role in affecting clozapine exposure are available. A TDM repository was analyzed: clozapine and vitamin D levels measured with liquid chromatography were considered. 1261 samples obtained from 228 individuals were evaluated: 624 patients (49.5%) showed clozapine plasma levels in therapeutic range (350-600 ng/mL). Clozapine toxic plasma levels (>1000 ng/mL) were more present in winter (p = 0.025), compared to other seasons. Concerning vitamin D, a sub-analysis of 859 samples was performed: 326 (37.81%) were deficient ( ng/mL), 490 (57.12%) had insufficient concentrations (10-30 ng/mL), while 43 (5.02%) had sufficient (>30 ng/mL) levels. A correlation between vitamin D and clozapine plasma levels (p = 0.007, Pearson coefficient=0.093) was observed. The role of seasonal variation in clozapine plasma exposure in psychiatric patients treated with clozapine was suggested. Further studies in larger cohorts are needed in order to clarify these aspects.

Gabapentin in antipsychotic-induced tardive dyskinesia: results of 1-year follow-up.

BACKGROUND: In a previous study, improvement of antipsychotic-induced blefarospasm and involuntary oral-mandibulo movements were observed with the use of the anticonvulsant drug gabapentin among affectively ill patients who had been exposed to maintenance neuroleptics. The results reported in the present paper represent the sequel to the previous study. METHODS: The purported efficacy of gabapentin in the treatment of tardive dyskinesia has been assessed in an open design 1-year follow-up study, in which 30 schizoaffective, bipolar I and schizophrenic patients from seven Italian centres were evaluated by means of AIMS. The results showed a statistically significant time-related decrease in AIMS scores. The mean percentage of improvement at AIMS was 47.5+/-18.2%. An improvement of more than 35% after 1 year in 76% of the subjects who completed the trial (n=25) and in 63.3% of the entire sample admitted to the study was revealed. LIMITATION: Open trial. CONCLUSION: The introduction of new antipsychotic drugs has probably already limited the problems related to tardive dyskinesia. However, this type of side-effect is also observed during the course of treatment with atypical neuroleptics albeit with a lesser frequency. The fact that gabapentin treatment may have further improved clinical conditions of patients in whom therapeutic protocols had already been modified, appears to suggest exertion of a possible synergic action by the new neuroleptics on tardive dyskinesia.