[New antidepressive drugs]. / Neue Antidepressiva.

Five of the available eight substance groups known as antidepressants has been developed during the last years: selective serotonin reuptake inhibitors (SSRI), selective serotonin and norepinephrine reuptake inhibitors (SNRI), serotonin antagonists, reversible selective inhibitors of monoaminooxidase A (RIMA) and St. Johns word. Two main ideas were important for their development: more specific biochemical effects and less side effects. This development is going further. During the next years at least three new substance groups with new biochemical effects will come on the market. The growing spectrum of antidepressants is important for avoiding therapy resistant depression.

[Pharmacologic treatment of depression]. / Pharmakologische Depressionsbehandlung.

The pharmacological treatment of depression is focussed on antidepressants. Different substance groups with different biochemical mechanisms and side effects have antidepressant effects. Based on these different substances the pharmacological treatment of depression has become more and more differentiated. The combination of antidepressants and other drugs (lithium, carbamazepine, benzodiazepines, stimulants, antipsychotics, hormones) offers additional possibilities. The combination with other biological treatments of depression enlarges the spectrum of treatments. The inclusion of non-biological therapies makes the therapeutic possibilities with proven antidepressant efficacy rich and powerful.

[New psychotropic drugs--is only the price new?]. / Neuere Psychopharmaka--ist nur der Preis neu?

In this article a complete overview on all antidepressants and antipsychotics available at present is presented. The effects and side effects of the individual substance classes are systematically discussed and possible interactions stressed. Because of the great variety of available substances an appropriate medication may be found for every case.

Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients.

The use of psychostimulants as an adjuvant therapy in treatment-resistant depression is not very common nowadays and has been the subject of much criticism. This article gives a brief review of the literature and reports on the findings from a retrospective study carried out in 65 depressed patients treated with psychostimulants (amphetamine and methylphenidate) in addition to conventional antidepressants. Thirty-eight out of 65 patients showed significant improvement, in particular with respect to energy mood, and psychomotor activity. The best response to psychostimulants was seen in inhibited types of depression and in combination with a tricyclic antidepressant. None of the patients developed drug dependency. The incidence of side effects was low, and agitation and restlessness improved with an additional short-term treatment with benzodiazepines. It is concluded that the rapid onset of action (2-3 hours) after administration may help cover the therapeutic latency period of conventional antidepressants and probably potentiates their effect. In view of their potential benefits in treatment-resistant depressive states, psychostimulants should be tried more often.

Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine.

Steady state concentrations of (S)- and (R)-mianserin and desmethylmianserin were measured in 21 homozygous extensive metabolizers (as determined by genotyping for mutations 3 [or A] and 4 [or B]), in seven heterozygous extensive metabolizers and in one poor metabolizer of debrisoquine, as well as in one patient receiving very high doses of mianserin (360 mg/day) and fluoxetine (160 mg/day), a strong cytochrome P450IID6 inhibitor. The mean dose of mianserin was (mean +/- SD, range: 67 +/- 63, 10 to 360 mg/day). High dispersions of the (S)/(R)-mianserin and desmethylmianserin ratios were observed (mean +/- SD, range: 2.10 +/- 1.01, 0.64 to 4.76, and 0.29 +/- 0.14, 0.08 to 0.57, respectively). The highest (S)/(R)-mianserin ratio was calculated for the poor metabolizer (4.76) agreeing with those results of a single-dose study with poor and extensive metabolizers of debrisoquine, in that the cytochrome P450IID6 is probably involved in the metabolism of mianserin with an enantioselectivity for the (S)-enantiomer. Nevertheless, the mean concentration-to-dose ratios for (S)- or (R)-mianserin or desmethylmianserin were not significantly different between homozygous and heterozygous and extensive metabolizers, and no particular values were measured in the poor metabolizer nor in the patient receiving fluoxetine. Furthermore, the (S)/(R)-mianserin ratio measured in the PM was only slightly higher than the second highest ratio (3.85) of an homozygous extensive metabolizer, whereas no particular value (2.92) was calculated for the patient taking fluoxetine. Finally, no significant differences in (S)/(R)-mianserin or (S)/(R)-desmethylmianserin were calculated between homozygous and heterozygous extensive metabolizers. Although the number of patients included in this study is too low to allow definite conclusions, the results suggest that the debrisoquine genotype has only a moderate influence on the steady state concentrations of the enantiomers of mianserin and desmethylmianserin.

[Recognizing anxiety and successful treatment]. / Angst erkennen und erfolgreich behandeln.

It is an important task of the family doctor (general practitioner) to recognise anxiety disorders and treat them successfully. Patients and their relatives must be informed about the available effective treatment possibilities and about the right moment for their application in an individual patient. In difficult cases the family doctor can consult a psychiatrist. Based on the incidence of anxiety disorders it is not possible to send each patient to a psychiatrist for treatment. In many cases this is not necessary, a consilium or a telephone discussion is sufficient.

A case of serotonin syndrome caused by venlafaxine and lithium.

Serotonin syndrome occurred under treatment with average dose of Venlafaxine and lithium in a 50 year-old female patient with a history of sensitiveness to SSRIs. Plasma levels of Venlafaxine and its metabolite were within reference range. Parmacogenetic evaluation indicated normal metabolic pathway.

Speaking behavior and voice sound characteristics associated with negative schizophrenia.

Based on a sample of 42 chronic schizophrenic patients and 42 carefully matched controls, we investigated potential relationships between acoustic variables on the one hand, and negative syndromes, positive syndromes and affective disturbances, on the other. A set of 12 acoustic variables automatically assessed in a standardized experimental setting allowed an almost perfect discrimination between schizophrenic patients and normal subjects. Acute side-effects of medication did not explain this finding. However, the question of whether the observed changes in speaking behavior and voice sound characteristics were caused by long-term neuroleptic treatment, for example, as a consequence of tardive dyskinesia, could not be answered by our investigation. In view of a biological validation of the negative-positive model of schizophrenia, the reliability of various psychopathological subscales was tested through repeated assessments at 14 day intervals. We found most psychopathology scores to be sufficiently stable and reproducible over time, thus representing a suitable basis for the estimation of severity with respect to the negative and positive component of schizophrenia. Using the first measurements as training samples and the second measurements of 14 days later as test samples, discriminant analysis yielded conclusive proof of a close relationship between acoustic variables and the severity of the negative and positive component of schizophrenia. In particular, by means of "objective" acoustic variables and under the constraint of reproducibility, 75.9% of patients were correctly classified as low or high scorers with respect to the negative syndrome, 71.9% of patients with respect to the positive syndrome, and 79.4% of patients with respect to their depressive symptomatology.

[Are there antidepressants specially indicated in certain depressive disorders?]. / Gibt es Antidepressiva, die bei bestimmten Depressionen speziell indiziert sind?

Treatment for depression has improved and several well tolerated antidepressants have been developed. The diagnosis is less important for the choice of treatment than the severity of the symptoms. Antidepressants are indicated if a depression is of at least moderate severity. For many years attempt has been made to find specific criteria for the choice of the "right" antidepressant. At present the scientific results do not allow unequivocal formulation of criteria for the differential indication of antidepressants. When treating patients we have nevertheless to decide which antidepressants to prescribe. Based on scientific results and long therapeutic experience, the author indicates which antidepressants may be more successful in which depression (retarded depression, agitated depression, delusional depression, suicidal ideas, anxiety, obsessive compulsive symptoms, eating disorders and atypical depression).

The role of moclobemide in endogenous depression: a survey of recent data.

Earlier studies demonstrated that moclobemide has good efficacy as an antidepressant. Its efficacy was comparable to reference antidepressants, both in endogenous and non-endogenous depression. A meta-analysis was performed of recent data from more than 2000 patients who had participated in double-blind trials with moclobemide and comparison drugs. Based on HAMD-17 baseline scores, the sample was divided into three groups according to the severity of depression. In all three, moclobemide was as effective as comparison drugs, both in endogenous and non-endogenous depression. The antidepressant efficacy of both moclobemide and reference drugs was more pronounced in endogenous than in non-endogenous depression, whatever the severity.

Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.

The metabolism of most tricyclic antidepressants and some phenothiazine neuroleptics is under the genetic control of hepatic cytochrome P-450IID6, which also regulates the metabolism of dextromethorphan. This study investigated the effect of treatment with amitriptyline or thioridazine on testing for genetically regulated efficiency of the metabolism of dextromethorphan and mephenytoin. One group of 33 patients was treated with 150 mg amitriptyline a day (the AMI group); 25 other patients received a daily dose of thioridazine, either 200 mg (200-THD group; n = 7) or 400 mg (400-THD group; n = 18). Before and after 10 days of this treatment, all patients were tested with 25 mg dextromethorphan and 100 mg mephenytoin to determine their pharmacogenetic status with respect to their hepatic drug oxidizing systems (cytochrome P-450IID6 and P-450 MP). Two patients were poor metabolizers (PMs) of dextromethorphan and three of mephenytoin. Treatment with either psychotropic drug was without significant effect on the metabolism of mephenytoin, but both amitriptyline and thioridazine increased significantly the metabolic ratio of dextromethorphan/dextrorphan. Thioridazine had the effect of changing the pharmacogenetic status of 15 efficient metabolizers of dextromethorphan to poor metabolizers; amitriptyline did not have such an effect. There was no significant correlation between day-11 plasma levels of thioridazine, mesoridazine, or sulforidazine and the metabolism of dextromethorphan, but there was a correlation between the metabolism of dextromethorphan and plasma levels of amitriptyline and nortriptyline. Amitriptyline (p less than 0.05), but not thioridazine, decreases the ratio of conjugated/total dextrorphan in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Methodology of measuring the efficacy of antidepressants--European viewpoint.

The 1988 Consensus Conference on the Methodology of Clinical Trials of Antidepressants developed a European viewpoint on the methodology of measuring the efficacy of antidepressants. Placebo-controlled, parallel group trials are necessary but problematic. To test the efficacy of a new antidepressant, only patients with recognized depressive disorder of at least moderate severity should be included. In double-blind trials comparing a novel antidepressant with a well known reference drug, effective doses of the reference drug should be used. Efficacy can best be demonstrated in non-treatment-resistant patients. The recommended length of trials for proof of antidepressant efficacy is at least 4 weeks.

[Pharmacotherapy of depression]. / Pharmakotherapie der Depression.

Four cardinal rules for pharmacotherapy of depression are discussed: 1. Severity of depression is the main criterion for the decision to treat by drugs. 2. The profile of side effects of antidepressants furnishes the arguments for drug selection. 3. Sufficiently high doses are the main prerequisite for rapid and strong response. 4. The sooner the treatment with an antidepressant is initiated, the earlier an effect of treatment can be expected.

Affective state and voice: results of a pilot study with six depressive patients.

As part of an investigation into the nonverbal information in human speech, a pilot study with depressive patients was designed in order to model the global affective state as a function of time and in terms of speech parameters. Over a two-week period, six patients were examined six times at two-day intervals under comparable experimental conditions. The psychopathologic status of these patients was assessed during a psychiatric exploration half an hour before the actual examination was carried out. Besides the solution of the baisc methodological problems, a principal goal of this study was to test the ability and cooperation of depressive patients when asked to speak in the laboratory. It turned out that even scalar parameters such as energy and dynamics give insight into the intraindividual variation of global affective state, and that the examination procedure is practicable even it patients are considerably handicapped by their illness.