Use of high doses of quetiapine in bipolar disorder episodes are not linked to high activity of cytochrome P4503A4 and/or cytochrome P4502D6.

The use of quetiapine for treatment of bipolar disorders at a higher dosage than the licensed range is not unusual in clinical practice. Quetiapine is predominantly metabolised by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability observed in quetiapine dosage. The aim of the present study is to evaluate if the use of high dosages of quetiapine in some patients, as compared to patients treated with a dosage in the licensed range (up to 800 mg/day), could be explained by a high activity of CYP3A4 and/or of CYP2D6. CYP3A4 activities were determined using the midazolam metabolic ratio in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage (mean ± SD, median; range: 1467 ± 625, 1200; 1000-3000 mg/day) and 11 with a normal quetiapine dosage (433 ± 274, 350; 100-800 mg/day). One patient in the high dose and one patient in the normal dose groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4 activities were not significantly different between the two groups (midazolam metabolic ratio: 9.4 ± 8.2; 6.2; 1.7-26.8 vs 3.9 ± 2.3; 3.8; 1.5-7.6, in the normal dose group as compared to the high dose group, respectively, NS). The use of high quetiapine dosage for the patients included in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6.

Off-label utilization of antidepressants.

UNLABELLED: While antidepressant prescription rules are established for approved indications by large-scale studies, off-label utilization naturally often lacks the validation by large scientific databases, and is at its best based on expert consensus. The aim of the present survey was to study the prescription habits of hospital psychiatrists with regard to antidepressants, comparing patients treated for depressions and anxiety disorder with patients receiving off-label antidepressant treatment. METHODS: Data on drug use for this study were based on 6 reference days from April 1999 to November 2001 in the 98-bed psychiatric hospital of the University of Lausanne, Switzerland. The drug prescriptions of 174 patients were assessed. RESULTS: Whereas the diagnosis did not influence the choice between newer or older antidepressants, patients presenting an anxiety disorder were 4.5 times more likely (p<0.05) and patients with other diagnoses 8 times more likely (p<0.001) to receive an antipsychotic comedication compared to patients whose primary diagnosis was a depressive disorder. Also, patients receiving concomitantly a nonbenzodiazepine hypnotic were less likely to be prescribed an older antidepressant (p<0.05). While patients with anxiety disorder and those with major depression received their antidepressants at comparable doses, patients with an off-label indication were treated preferentially with lower doses. CONCLUSIONS: The results of this survey suggest, that the prescribing hospital psychiatrists developed preferences with regard to the choice of the antidepressant class, which they then used for both registered and off-label indications. They then seemed to adapt the dose and the comedication according to the diagnosis, confirming the initial study hypothesis.

Topiramate for smoking cessation.

Due to its AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate antagonism, topiramate would be particularly interesting in addiction treatment. Flexible-dose topiramate was prescribed to 13 smokers (10 smokers who wanted to stop smoking, and three who received topiramate for other reasons). Six out of 13 smokers were abstinent at 2 months and two more subjects had reduced their cigarette consumption by >50%. With one exception, temporary reduction of the number of smoked cigarettes preceded definitive abstinence at month 2. Three more subjects who achieved a momentary reduction had, however, to interrupt the treatment due to intolerable side-effects. Controlled trials are needed to confirm these preliminary observations.