Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram.

From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications.

[New antidepressive drugs].

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.

[Pharmacologic treatment of depression].

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.

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.

[New psychotropic drugs--is only the price new?].

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.

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.

[Recognizing anxiety and successful treatment].

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.

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.

[Are there antidepressants specially indicated in certain depressive disorders?].

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.

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.

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).

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.

[Pharmacotherapy of 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.

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.

Effect of neuroleptics on positive and negative symptoms and the deficit state.

The concept of negative symptoms tries to operationalize a deficit syndrome observed in schizophrenia, but also in other disorders. The instruments for the measurement developed so far are unclear in their dimensional structure and validity. Further methodological development is needed.

Acetylation of maprotiline and desmethylmaprotiline in depressive patients phenotyped with sulfamidine, debrisoquine, and mephenytoin.

A gas chromatographic/mass spectrometric method (using either electron impact or chemical ionisation with methane or ammonia) is described for the quantitative analysis of maprotiline (MP, Ludiomil), N-acetylmaprotiline (AcMP) and N-acetyldesmethylmaprotiline (AcDMP) in whole blood or plasma. In two groups (A and B) of 82 and 53 depressive patients treated clinically with MP for 10 and 21 days, respectively, plasma and whole blood MP was monitored during the treatment. In group A, all subjects were phenotyped with debrisoquine and mephenytoin, and 44 with sulfamidine.

Unsolved problems in the pharmacotherapy of depression.

Five unsolved problems in the pharmacotherapy of depression are discussed: (a) it is not possible to differentiate endogenous and nonendogenous depression; (b) a selective efficacy of serotonin and noradrenaline reuptake inhibitors cannot be demonstrated; (c) the relationship between plasma levels and antidepressant effect is still unclear: plasma levels are influenced by pharmacogenetic factors, age, route of application, and concomitant treatment with other drugs; (d) evidence is growing for the development of tolerance towards therapeutic effects of antidepressants; (e) no pretreatment variable allows prediction of treatment response: the best predictor is the initial response to treatment.