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.

Does substance use disorder affect clinical expression in first-hospitalization patients with schizophrenia? Analysis of a prospective cohort.

Although several papers reported a wide range of negative outcomes among patients with both schizophrenia and Substance Use Disorder (SUD), only a few studies evaluated the impact of SUD on psychopathology and thus on the length of first-hospitalization. The aim of the present study was to compare clinical expression of first-episode of schizophrenia between inpatients with and without SUD, giving close attention to the length of stay. One hundred and thirty inpatients at first-episode of schizophrenia were assigned to either SUD or not SUD group depending on SUD diagnosis and were assessed through BPRS at admission, during hospitalization and at discharge. Cross-sectional and longitudinal statistical analysis were performed to investigate differences between groups and also a linear regression was used to evaluate relationship between length of stay and BPRS scores. SUD group showed more disorganization at admission, less marked improvement of symptoms (disorganization, thought disturbance, anergia), and longer hospital stay than not SUD group. Moreover BPRS total score during hospitalization was a significant positive predictor for length of stay. Taken together, these findings suggest that SUD patients have a more severe and drug-resistant expression of schizophrenia, hence, they need longer treatment to achieve the overall symptoms improvement required for discharge.

Premorbid conditions and precipitating events in early-onset panic disorder.

This study investigates differences in premorbid conditions and in the role of triggering events in the onset of early-onset versus adult-onset panic disorder (PD). Two hundred forty-one outpatients with a principal diagnosis of PD (DSM-IV) were evaluated using a semistructured interview to generate axis I and axis II diagnoses according to DSM-IV, and to collect family history of psychiatric disorders and life events. For statistical analysis the sample was subdivided in two groups according to age at onset (< or =18 years or >18 years). Early-onset and adult-onset patients with PD do not differ in the severity of the disorder and in the interference with their overall functioning. Early-onset patients have (1) higher familial loading for psychiatric disorders in general and for PD in particular; (2) higher frequency of preceding anxiety disorders, dysmorphophobia, and bulimia nervosa; and (3) higher comorbidity rates for personality disorders and particularly for disorders of the "anxious-fearful" cluster. The data we found on life stress indicate that the environmental factors play a major role in the development and/or in precipitating the onset of adult-onset PD. Our findings suggest that the early-onset form of PD seems to be more characterized by endogenous components compared to the adult-onset form.