Depression: Brøsen K

Sorensen L, Nielsen B, Stage KB, Brøsen K, Damkier P. · Amgros I/S, Dampfaergevej 22, København Ø, Denmark. · Nord J Psychiatry. · Pubmed #18622885 No free full text.

Abstract: The objective of the study was to develop, implement and evaluate two treatment algorithms for schizophrenia and depression at a psychiatric hospital department. The treatment algorithms were based on available literature and developed in collaboration between psychiatrists, clinical pharmacologists and a clinical pharmacist. The treatment algorithms were introduced at a meeting for all psychiatrists, reinforced by the project psychiatrists in the daily routine and used for educational purposes of young doctors and medical students. A quantitative pre-post evaluation was conducted using data from medical charts, and qualitative information was collected by interviews. In general, no significant differences were found when comparing outcomes from 104 charts from the baseline period with 96 charts from the post-intervention period. Most of the patients (65% in the post-intervention period) admitted during the data collection periods did not receive any medication changes. Of the patients undergoing medication changes in the post-intervention period, 56% followed the algorithms, and 70% of the patients admitted to the psychiatric hospital department for the first time had their medications changed according to the algorithms. All of the 10 interviewed doctors found the algorithms useful. The treatment algorithms were successfully implemented with a high degree of satisfaction among the interviewed doctors. The majority of patients admitted to the psychiatric hospital department for the first time had their medications changed according to the algorithms.

Brøsen K. · Syddansk Universitet, Institut for Sundhedstjenesteforskning, Klinisk Farmakologi, Odense C. · Ugeskr Laeger. · Pubmed #17594829 No free full text.

Abstract: Pharmacoepidemiological studies have shown that there are approximately 30% more adverse drug reaction reports on women than on men. The precise reason for this sex difference is unknown. It could either be due to increased drug use in women compared with men, increased polypharmacy and hence drug-drug interactions, a lower threshold for accepting adverse drug reactions in women or it could be due to true sex differences in pharmacokinetics or pharmacodynamics which render women more susceptible to adverse drug reactions. Sex differences in pharmacokinetics and in particular cytochrome P450 activity have been reported. Thus, CYP3A4 activity is increased in women compared with men, while CYP1A2 activity is lower in women than in men. The glucuronidation of drugs also appears to be slower in women than in men. In general, pharmacodynamic sex differences are less well studied. Drug-induced torsades des pointes occur twice as frequently in women as in men. There do not seem to be any sex differences with regard to placebo effect in pain or depression treatment.

Otto M, Bach FW, Jensen TS, Brøsen K, Sindrup SH. · Department of Neurology, Odense University Hospital, University of Southern Denmark, Sdr. Boulevard 29, Odense C, Denmark. · Pain. · Pubmed #18547727 No free full text.

Abstract: Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch- or pressure-evoked pain, lancinating pain, constant burning or deep aching pain) by the use of 0-10-point numeric rating scales. Changes in health-related quality of life and severity of depression were measured with the SF-36 and the Major Depression Inventory (MDI). Forty-one patients were included in the data analysis. Patients reported a better pain relief during treatment with escitalopram compared with placebo (p=0.001). Total pain and different pain symptoms were lower during escitalopram treatment (p=0.001-0.024). The Number needed to treat (NNT) to obtain one patient with good or complete pain relief was 6.8. Health-related quality of life and depressive symptoms were unaltered (p=0.086-1.0). Five patients (10.4%) discontinued the study because of adverse effects during escitalopram. This study found a pain-relieving effect of escitalopram in patients with painful polyneuropathy, but a clinically relevant effect was obtained in only few patients. Currently, the drug cannot be recommended as a standard treatment in neuropathic pain.

Kirchheiner J, Brøsen K, Dahl ML, Gram LF, Kasper S, Roots I, Sjöqvist F, Spina E, Brockmöller J. · Institute of Clinical Pharmacology, Charité, Humboldt University of Berlin, Germany. · Acta Psychiatr Scand. · Pubmed #11531654 No free full text.

Abstract: OBJECTIVE: This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring. METHOD: Our literature search covered 32 antidepressants marketed in Europe, Canada, and the United States. We evaluated studies which had compared pharmacokinetic parameters of antidepressants among poor, intermediate, extensive and ultrarapid metabolizers. RESULTS: For 14 antidepressants, distinct dose recommendations for extensive, intermediate and poor metabolizers of either CYP2D6 or CYP2C19 were given. For the tricyclic antidepressants, dose reductions around 50% were generally recommended for poor metabolizers of substrates of CYP2D6 or CYP2C19, whereas differences were smaller for the selective serotonin reuptake inhibitors. CONCLUSION: We have provided preliminary average dose suggestions based on the phenotype or genotype. This is a first attempt to apply the new pharmacogenetics to suggest dose-regimens that take the differences in drug metabolic capacity into account.