Depression and cognitive impairment in the elderly: a multicentre study.

The present study, conducted in collaboration between the Departments of Psychiatry in Swiss Universities and the World Health Organization, had two main goals: to develop assessment methods which could subsequently be used in the Swiss centres in a standard manner; and to make arrangements for continuing collaboration between the centres in Switzerland and the acquisition of new knowledge about the distinctions between depression and cognitive impairment. For this aim, three different groups of elderly patients of either sex were selected during the period of November 1989 to July 1991 for inclusion in the study. The first two groups included the first ten patients of either sex over 60 years of age consecutively contacting the participating institutions and showing depression with or without clinically significant symptoms of cognitive impairment; the control group included patients showing no depression or clinically significant symptoms of cognitive impairment. A total of 125 patients were included in the initial evaluation, 69 of which were reassessed at a seven-month follow up (on average). Each patient was administered a number of clinician-rated or self-report instruments for the assessment of depression, cognitive impairment, disabilities, physical status and onset of disorders. The study has shown that a variety of instruments can be used for the reliable assessment of depression or cognitive impairment in the elderly; but the instruments for the assessment of depression differentiate only poorly between patients with or without cognitive impairment. Because of the importance of identifying both depressed and cognitively impaired patients among the elderly, different assessment instruments targeted at the different symptom clusters need to be administered simultaneously.

Biological study of alcohol dependence syndrome with reference to ethnic difference: report of a WHO Collaborative Study.

Inherited deficiency of acetaldehyde dehydrogenase type I (ALDH-I) was found in 43% (50/117) of normals, 33% (27/82) of schizophrenics, but only 4% (5/113) of alcoholics among Japanese. The ALDH-I deficiency was never found, however, in 146 mostly schizophrenic subjects from Europe (Basel, Moscow, Zagreb), Australia (Nedlands), India (Lucknow), Morocco (Casablanca) and Mexico (Mexico City). It was demonstrated that ALDH-I deficiency produces the flushing syndrome which inhibits the development of drinking habit and alcohol dependence syndrome.

[Treatment of drug-resistant depression by intravenous administration of antidepressants]. / Lechenie rezistentnoi depressii putem vnutrivennogo vvedeniia antidepressantov.

The proportion of depressed patients no longer responding adequately to oral antidepressive medication combined with psychotherapy now amounts to as much as 15%. Depressive states failing to lift in response to antidepressants are referred to in Europe as "therapy-resistant". Before initiating some further form of treatment in a case of therapy resistance the diagnosis as well as the antidepressive treatment given hitherto (dosage, activity profile, compliance) should be reappraised. Where the diagnosis of "therapy-resistant depression" is confirmed, intravenous infusions of antidepressants in combination with psychotherapy have been found to offer the best prospects of success. With the help of daily infusions of maprotiline (ludiomil) and/or clomipramine (anafranil) it proved possible in over 1,000 patients suffering from therapy-resistant depression to achieve a remission in 60% and a marked improvement in 20%. At various research centres in Europe where intravenous drip infusions were administered in relatively low dosages, a more rapid onset of action was observed with fewer side effects, as well as higher plasma concentrations (thanks to avoidance of the first-pass effect) and no problems with respect to compliance.

Dose relationships of morning bright white light in seasonal affective disorders (SAD).

Bright white full spectrum light (greater than 2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.

Light treatment of seasonal affective disorder in Switzerland.

Seasonal Affective Disorder (SAD) has been characterised by two or more depressive episodes in autumn or winter (with remission the following spring or summer), decreased energy, increased sleep, increased appetite, weight gain and carbohydrate craving. SAD patients were identified in a Swiss-German population; 22 participated in a light-therapy protocol (1 week bright white light 2,500 lux or dim yellow light 250 lux, from 06-08 h and 18-20 h). Both observer and self-ratings indicated a significant diminution of depressive symptoms with both lights. One week after withdrawal from yellow light, depression ratings relapsed to previous values; remission lasted longer after bright white light. Global VAS self-rating scales for "mood" and "well-being" however, and the Hamilton scale for atypical SAD symptoms, differentiated clearly between bright and dim light: only bright light showed an improvement that persisted after withdrawal. These results suggest that even though a placebo effect cannot be excluded, 4 h explicit light exposure/day may not be a negligible quantity. Light treatment promises to be a useful non-pharmacological intervention in certain forms of depressive illness.

Treatment for therapy-resistant depression.

Thanks to progress in the diagnosis and treatment of depression it is now possible for most cases to be treated on an out-patient basis. Only 15-20% of patients require hospitalisation, most of them because their depression has proved resistant to therapy. To overcome therapy-resistance, the following methods of treatment are available: In therapy-resistant endogenous and psychogenic depressions, mono-infusion therapy is the treatment of choice; it can also be administered on an out-patient basis. In extremely intractable cases, it is advisable to resort to combined infusion therapy, preceded by five days of relaxation therapy with oral doses of a neuroleptic, and possibly reinforced by medication with 5-hydroxytryptophan (the precursor of serotonin) or by sleep deprival. In therapy-resistant cases of so-called masked depression, marked by overtones of anxiety and hypochondriasis, infusions of maprotiline are indicated, because this anti-depressant exerts a relaxing and mildly anxiolytic action, has a stabilising influence on the autonomic nervous system, and produces a mood-brightening effect. In patients who are apathetic and devoid of drive and suffering from involutional depression or depression of old age, infusion therapy plus administration of an MAO inhibitor can be recommended. Combination of an antidepressant with a neuroleptic agent also displaying certain antidepressive properties is really indicated only in the rare cases of schizo-affective psychosis. Electroconvulsive therapy should be employed only as a last resort in extremely retarded and apathetic patients with strong suicidal tendencies, and the indication for ECT should be established with the utmost reserve.

[Multifactorial treatment of depression]. / Multifaktorielle Depressionsbehandlung.

According to the results of all recent epidemiological enquiries, the number of cases of depression diagnosed is steadily increasing, especially in urban communities. Parallel with this increase, there has been a clear tendency for the symptomatology of depression to change in the direction of somatization. Essential prerequisites for the success of treatment of depression are not only a carefully established diagnosis but - ordinarily - also combination of the psycho-, pharmaco-, socio- and physiotherapy. In case of depressive states the nosological diagnosis determines the choice of basic therapy and the phenomenological diagnosis the selection of the right antidepressant. All antidepressants have a delayed onset of action and are apt to provoke side effects of varying severity. Prior to the initiation of treatment the patient's attention should be drawn to the possibility of side effects. The basic principles of psychotherapy for depression are briefly outlined. The possibilities to treat therapy-resistant depressions with a combined infusion therapy are prescribed. The recent improvements in biological psychiatry are shown.

[Treatment of therapy-resistant depressions. Results of combined infusion treatment]. / Zur Behandlung therapieresistenter Depressionen. Ergebnisse einer kombinierten Infusionstherapie.

230 patients with therapy-resistant depression were given intravenous drip infusion treatment with clomipramine (a predominantly serotonin-uptake inhibitor) and maprotiline (a predominantly noradrenaline-uptake inhibitor), preceded by a five-day tranquilizing regimen with a neuroleptic drug. During the treatment period of 10-20 days the patients were given one infusion daily, while later both antidepressants were taken orally. The neuroleptic drug was given at night from the start of the infusion phase to the end of hospitalization. After four weeks' treatment 68% of the endogenous depressives and 54% of the exhaustion depressives had completely remitted. In patients who fail to respond the infusion regimen can be repeated after carefully rechecking the patient's diagnosis. After discharge and resumption of work the antidepressants should be reduced stepwise. A prerequisite for success in the management of refractory depression is the combination of drug administration with adequate psychotherapeutic and physiotherapeutic measures. The infusion regimen is relatively easy to administer, can be given on an outpatient basis and could be the treatment of choice in the future not only for treatment-resistant depression but also for patients whose depressive state requires rapidly effective antidepressive measures. In view of the encouraging experience obtained to date with this treatment, the World Health Organization is conducting an international collaborative research project involving 12 psychiatric centres to elucidate the effectiveness of intravenous infusion therapy in different races with different dietary habits and varying climatic conditions.

Changes in EEG, blood levels, mood scales and performance scores during long term treatment with diazepam, phenobarbital or placebo in patients.

1. The patient population consisting of fifteen patients was divided into three groups, namely: diazepam group, phenobarbital group and placebo group. After three weeks the medicated groups were switched to placebo for a week and the placebo group was given phenobarbital. 2. The parameters to be assessed once a week comprised frequency-analyzed EEG recordings, performance in two attention tests and subjectively estimated mood modalities. 3. The EEG analysis suggested that EEG patterns: a) were drug-dependent, with a differential distribution for each drug of the four frequency bands analyzed; b) showed no change during the three-week treatment period; c) changed on cessation of medication or on switch from placebo to active medication; d) were task-dependent and changed in a systematic way with the level of activation (stress, vigilance or relaxation). 4. The results would allow a better understanding of the clinical course, the choice of therapeutic measures and of the underlying mechanisms of action.

Driving ability of depressive patients under antidepressants.

A group of twenty depressive patients was compared during a 3-4 month course of antidepressant therapy (Maprotiline: n = 6, age = 46.1; dibenzepin: n = 4, age = 43.0; lithium: n = 6, age = 44.5; "mixed" (maprotiline, dibenzepin trimeprimine): n = 4, age = 50.2) with a healthy control group (n = 32, age = 38.2) for subjective assessment of their depressive mood and performance as well as objective measurement of variables relating to driving behaviour. The measurements were taken 2-4 weeks after a pre-treatment period (day 1) and after 2-3 months of further therapy (day 2). During therapy, all patients felt "less depressive" and "more capable" in subjective terms. All patient groups made learning progress in the objectively measured variables (psychomotor co-ordination and attentiveness tests). By day 2, the patient groups had almost reached the performance level of the control group, providing they received antidepressant therapy (regardless of the action profile) which was suitable for the basic disorder and the symptoms, and therapy was successful in the opinion of the physician. It may be concluded that depressive patients, assuming suitable antidepressant treatment and good response, are capable of driving while under maintenance therapy.