The Hospital Anxiety and Depression Scale: low sensitivity for depression screening in demented and non-demented hospitalized elderly.

BACKGROUND: We currently use the depression subscale (HADD) of the Hospital Anxiety and Depression Scale (HADS) for depression screening in elderly inpatients. Given recent concerns about the performance of the HADD in this age group, we performed a quality-control study retrospectively comparing HADD with the diagnosis of depression by a psychiatrist. We also studied the effect of dementia on the scale's performance. METHODS: HADS produces two 7-item subscales assessing depression or anxiety. The HADD was administered by a neuropsychologist. As "gold standard" we considered the psychiatrist's diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Patients older than 65 years, assessed by both the HADD and the psychiatrist, with a clinical dementia rating (CDR) score lower than 3, were included. The effect of dementia was assessed by forming three groups according to the CDR score (CDR0-0.5, CDR1, and CDR2). Simple and multiple logistic regression models were applied to predict the psychiatrist's depression diagnosis from HADD scores. Areas under the receiver operating characteristics curve (AUC) were plotted and compared by χ(2) tests. RESULTS: On both univariate and multiple analyses, HADD predicted depression diagnosis but performed poorly (univariate: p = 0.009, AUC = 0.60 (95% confidence interval (CI) = 0.53-0.66); multiple: p = 0.007, AUC = 0.65 (95% CI = 0.58-0.71)), regardless of cognitive status. Because mood could have changed between the two assessments (they occurred at different points of the hospital stay), the multiple analyses were repeated after limiting time interval at 28, 21, and 14 days. No major improvements were noted. CONCLUSION: The HADD performed poorly in elderly inpatients regardless of cognitive status. It cannot be recommended in this population for depression screening without further study.

Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression.

Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.

Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer.

A very long half-life of paroxetine (195 h instead of the usual value of around 16 h) was measured after an overdose with 2 g paroxetine and 1 g clorazepate in a patient who was an extensive cytochrome P4502D6 metabolizer. The patient recovered well without any clinically significant complications. A consequence of the close monitoring of paroxetine levels in this patient was that it was decided not to reintroduce any other antidepressant despite her suicide attempt, until normal levels of paroxetine had been reached, which took over 1 month.