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Objective: The aim of this study was, on the basis of data from health-care registers, to describe the adequacy of psychopharmacological treatment in suicides. Method: Data on consecutive suicides in a Danish County (Funen) in the period of 1 April 1991–31 December 1995 were identified in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense University Pharmacoepidemiological Database. Results: Twenty-five per cent of the suicides previously hospitalized due to affective disorders and 3% of the suicides without psychiatric hospitalizations at all, received an apparently adequate treatment with antidepressants the month before suicide. Conclusion: The most striking finding was the insufficiency of treatment with antidepressants in the group of suicides without psychiatric hospitalization, in particular in light of the fact that depression is assumed to be present in at least 50% of all suicides.

CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: A first step towards subpopulation specific dosages.

In contrast to out-patients, hospitalized depressed patients have been reported to respond better to tricyclic antidepressants (TCAs) than to selective serotonin reuptake inhibitors (SSRIs) and moclobemide. This may be due to differences in the type of patients included in the trials. The hypothesis that hospitalized depressed patients have a different symptom profile to out-patients was tested by comparing 352 patients from three in-patient studies with 581 patients from three out-patient studies conducted in Denmark during the period 1980-1992. All patients had major depression and were evaluated using the Hamilton Depression Scale. The full version of the Newcastle Diagnostic Rating Scale (1965) was applied to 443 of the patients. In-patients were characterized by higher scores on the items 'depressed mood', 'suicidal impulses', 'work and interest (reduced)', 'retardation', 'distinct quality of depression', 'weight loss', 'feeling of guilt' and 'nihilistic delusions', and by lower scores on the items 'somatic complaints', 'hypochondriasis', 'psychological stressors' and 'anxiety'. In total, 76% of the in-patients and 40% of the out-patients had melancholic/endogenous depression. These findings may explain why TCAs are superior to SSRIs and moclobemide in hospitalized patients, since other data indicate that TCAs seem to be the most effective treatment for the melancholic/endogenous subtype.

The aim of this study was, on the basis of data from health-care registers, to describe the adequacy of psychopharmacological treatment in suicides.Data on consecutive suicides in a Danish County (Funen) in the period of 1 April 1991-31 December 1995 were identified in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense University Pharmacoepidemiological Database.Twenty-five per cent of the suicides previously hospitalized due to affective disorders and 3% of the suicides without psychiatric hospitalizations at all, received an apparently adequate treatment with antidepressants the month before suicide.The most striking finding was the insufficiency of treatment with antidepressants in the group of suicides without psychiatric hospitalization, in particular in light of the fact that depression is assumed to be present in at least 50% of all suicides.

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.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.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.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.

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.

In 37 consecutive depressed inpatients afternoon plasma cortisol (1500-1520 h) was measured in 3 ways: 1) spontaneously; 2) 2 h after oral administration of 60 mg oxazepam; and 3) 16 h after oral administration of 2 mg dexamethasone. Both oxazepam and dexamethasone caused a significant suppression of cortisol secretion. Spontaneous and suppressed cortisol levels correlated significantly to stress/distress items on the Hamilton Rating Scale for Depression (sum of items 8, 9, 10 and 12), whereas no correlations to age, or type of depression were found. In an earlier similar study of 35 patients both spontaneous and suppressed cortisol levels correlated significantly with age, type and severity of depression as well as with the stress/distress items. Those patients were older, more depressed (HRSD-17) and had higher stress/distress scores compared with the present sample of 37 patients. The consistent finding of a correlation with the stress/distress items suggest that this factor is important in relation to the hypersecretion of cortisol during depression and this may explain the limited diagnostic power of spontaneous and suppressed cortisol levels.

The WHO (World Health Organization) Depression Scale is a new rating scale developed to evaluate the complete clinical history and description of depression. Items of the WHO scale were transformed to cover the items of the two Newcastle scales that are designed to differentiate between endogenous and non-endogenous depressions. In 98 depressed inpatients examined prior to antidepressive therapy only moderate agreement between scores transformed to the two Newcastle scales was found. Also the distribution patterns of the scores on the two scales were different. In patients classified as endogenous on one or both scales a significant relationship between plasma levels of imipramine or clomipramine and antidepressive effect was found. In patients classified on both scales as doubtful - or non-endogenous depressions - no such correlation could be identified. The initial severity of depression, as defined by the Hamilton Depression Scale, was the same in endogenous, doubtful and non-endogenous depression according to the scores transformed to the two Newcastle scales.

The consistency of the Hamilton Depression Scale (HDS) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial when imipramine. By use of logistic models (Rasch) the consistency of the HDS has been considered across patient-variables as age, sex, plasma levels of imipramine, and diagnosis. The results showed that the original 17-item HDS was without adequate consistency, i.e. the total score of the sample of items was no one-dimensional measure of depressive states. However, a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively, although in some part of the analysis one of these items showed ceiling effect. It was concluded that the melancholia subscale (containing the items depressed mood, guilt, work and interests, retardation, psychic anxiety, and general somatic symptoms) can form the basis for further improvements in the field of quantitative rating scales for depressive states.

We have investigated Biegel's manic-state rating scale and found the interrater reliability high when the scale was administered both by nurses and psychiatrists. In our study of validation, we tested each item of the scale for calibration, ascending monotonicity and dispersion parallel to a global clinical assessment of the manic state. Six of the scale items were then found valid and those items differed from the valid items in studies of Biegel by including increased social contact. Like Biegel, we found a positive correlation between items concerned with depressed mood, indicating a fluctuation in the mood of manic patients during 8 hours of observation.

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.