Quetiapine and norquetiapine serum concentrations and clinical effects in depressed patients under augmentation therapy with quetiapine.

BACKGROUND: Quetiapine has been recently approved as an add-on therapy in the treatment of major depressive disorders in the case of inadequate response to antidepressant monotherapy. Thereby the antidepressant potential is attributed to the N-demethylated metabolite norquetiapine (NQ). The aim of this cross-sectional analysis was to relate quetiapine (Q) doses to serum concentrations of Q and its active metabolite and clinical effects. METHODS: Data were obtained from patients who had been treated with different antidepressants and augmented under naturalistic conditions with Q for whom blood level measurements were requested. RESULTS: For this analysis, 105 depressed patients were included who had been augmented with Q. The mean daily doses of Q were 222 ± 125 mg. Doses correlated significantly (P < 0.001) with the highly variable serum concentrations of both Q and NQ. Median serum concentrations of Q and NQ were 46 ng/mL (25th to 75th percentile 20-91 ng/mL) and 59 ng/mL (25th to 75th percentile 26-133 ng/mL), respectively. Concentrations per dose ranged from 0.10 to 0.58 ng·ml·mg for Q and from 0.17 to 0.59 ng·ml·mg for NQ. Most patients (55%) received comedications in addition to the antidepressant drug and Q. According to the clinical global impressions scale, 60% of the patients were either much (36%) or very much improved (24%). Receiver-operating characteristic analysis revealed no significant differences of serum concentrations between responders and nonresponders for NQ (P = 0.835) but a trend for Q (P = 0.056). CONCLUSIONS: Due to marked variability of Q and NQ concentrations in the blood, therapeutic drug monitoring may be helpful to identify pharmacokinetic peculiarities. The lack of correlation between serum concentrations of NQ and clinical improvement casts doubts on the concept that NQ is the pharmacologically active principle for the augmentation therapy.

The impact of reboxetine and mirtazapine on driving simulator performance and psychomotor function in depressed patients.

OBJECTIVE: The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed inpatients. METHOD: Forty depressed inpatients diagnosed according to DSM-IV-TR criteria were randomly assigned to treatment with either reboxetine (N = 20) or mirtazapine (N = 20). To control for retest effects in psychomotor measures, a group of 10 healthy controls was examined on the same time schedule. Participants were tested once before pharmacologic treatment and twice after initiation of treatment (days 7 and 14) with computerized tests related to car-driving skills. Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem, measuring visual perception, reactivity, stress tolerance, concentration, and vigilance. In addition, patients went through various risk simulations on a static driving simulator. Data were analyzed with nonparametric statistics and repeated-measures analysis of variance. The study was conducted from June 2004 through June 2006. RESULTS: Before onset of treatment with antidepressants, about 65% of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety. After 14 days of treatment with reboxetine or mirtazapine, patients improved in driving ability skills. Controlling for retest effects in psychomotor measures, data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity (all p < .01). Furthermore, the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine (all p < .05). Statistically significant differences between treatment groups could not be shown. CONCLUSION: Our results indicate that partially remitted depressed inpatients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives.

[Erythema multiforme caused by carbamazepine]. / Erythema exsudativum multiforme, ausgelöst durch Carbamazepin.

The antiepileptic carbamazepine can reduce aggressive behaviour and can be used as a mood stabilizer. We present a case report of a patient suffering from borderline personality disorder who was treated with carbamazepine and developed erythema multiforme.

[QTc-interval prolongation in therapy with atypical antipsychotics--results of an open, non-randomized survey]. / QTc-Zeitverlängerung unter Therapie mit atypischen Neuroleptika--Ergebnisse einer klinikinternen Anwendungsbeobachtung.

The introduction of Ziprasidone stimulated discussion about frequency and importance of QTc-interval prolongations with antipsychotic therapy. In an open non-randomized study we collected data about QTc-interval, electrolytes, vital parameters and associated clinical symptoms in patients treated with atypical antipsychotics. 33 patients were scanned and some moderate QTc-interval prolongations but no clinical events were seen. Due to scarcity of such events existing data should be completed by large scale clinical studies and by registration of severe QTc-interval prolongations and torsades de pointes in central drug monitoring systems.

[Prolactin Levels and Symptoms of Hyperprolactinemia in Patients Treated with Amisulpride, Risperidone, Olanzapine and Quetiapine] / Prolaktinplasmaspiegel und Häufigkeit der endokrinologischen Begleitwirkungen unter Therapie mit den atypischen Neuroleptika.

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same - in minor degree - for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

[Plasma prolactin level and incidence of adverse endocrinologic effects during therapy with atypical neuroleptics]. / Prolaktinplasmaspiegel und Häufigkeit der endokrinologischen Begleitwirkungen unter Therapie mit den atypischen Neuroleptika.

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.