Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disorder: A Prospective Observational Study.

BACKGROUND: The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility. METHODS: This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50-800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state. RESULTS: There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects. CONCLUSIONS: Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.

The Use of Zonisamide for the Treatment of Psychiatric Disorders: A Systematic Review.

OBJECTIVE: Traditional pharmacotherapy has undoubtedly improved the outcome of patients with psychiatric disorders, but partial efficacy or poor tolerability persists in a number of these subjects. Among different compounds, zonisamide has been used to address unmet needs of standard pharmacotherapy. The purpose of the present article is to provide a review about the use of zonisamide for the treatment of psychiatric conditions. METHODS: A research in the main database sources has been conducted to obtain an overview of the use of zonisamide in psychiatric disorders or associated conditions (obesity and smoking cessation). RESULTS: Most available data indicate the possible effectiveness of zonisamide for the treatment of acute phases of bipolar disorder, binge-eating disorder (BED), alcohol misuse, and obesity. A further assessment of the safety and tolerability of zonisamide is made necessary by the fact that, with the exception of BED, for all other disorders at least some data come from studies with combined pharmacological therapies. CONCLUSIONS: Zonisamide may have some utility, especially as an adjunctive therapy, for the management of acute phases and weight gain in bipolar disorder and for prevention of alcohol misuse. Preliminary evidence indicates zonisamide as a candidate compound for the treatment of BED and obesity. However, open-label design and small sample sizes of most available studies prevent from drawing sound conclusions about the utility of this compound in psychiatry.