Improved Alertness Is Associated with Early Increase in Serum Brain-Derived Neurotrophic Factor and Antidepressant Treatment Outcome in Major Depression.

Background/aims: In major depression cognitive impairment is common and may persist despite improvement in psychopathology. So far it is unclear how closely related improvement in cognitive functioning is to the clinical course of depression. Further, it is unclear whether recovery from cognitive impairment is linked to changes in serum brain-derived neurotrophic factor (sBDNF).

High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression.

Rationale: Major depressive disorder has been associated with low serum levels of brain-derived neurotrophic factor (sBDNF), which is functionally involved in neuroplasticity. Although sBDNF levels tend to normalize following psychopathological improvement with antidepressant treatment, it is unclear how closely sBDNF changes are associated with treatment outcome.

Objectives: To examine whether baseline sBDNF or early changes in sBDNF are predictive of response to therapy.

[Actual therapeutic options in the treatment of generalized anxiety disorders].

Among a variety of drugs used in the treatment of anxiety disorders, benzodiazepines and antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are at present the most established and prescribed. In fact, recent guidelines recommend the antidepressants SSRI and SNRI as well as pregabaline, a newly developed drug, as the 1st choice treatment in generalized anxiety disorder (GAD). However, antidepressants have several disadvantages (latency of onset of action, adverse effects and drug interactions) that should not be neglected.

Treating depression with different galenical drug formulations: Does it make a difference? The comparison of mirtazapine fast dissolving formulation (FDT) with conventional mirtazapine tablets (CT).

Objective. To assess clinical advantages of fast dissolving tablet (FDT) formulation of mirtazapine by comparison to conventional (CT) mirtazapine tablets in the treatment of depressed patients. Methods.

[Psychiatry].

Introduced this year on the Swiss market, duloxetine (Cymbalta) is a new antidepressant which inhibits the reuptake of noradrenaline and serotonin. Clinical studies have shown its efficacy in depression as well as in neuropathic pains (60-120 mg/day) with a good tolerability. In this paper are also included short reviews about the two large American studies developed by the National Institute of Mental Health in the fields of the treatment for depression (STAR-D) and of the antipsychotic treatments for schizophrenia (CATIE study).

The results of the Swiss observational study of the new, fast-dissolving mirtazapine formulation in depressed patients.

Objective. The purpose of the present study was to document the experience with the use of a new, fast-dissolving oral tablet (FDT, RemeronSolTab®) of mirtazapine, a NaSSA antidepressant, in the treatment of depressed patients in daily practice in Switzerland. Methods.

[Pharmacology of Alzheimer's disease: where do we go from here?].

Ten years after the introduction of the first drug for the treatment of Alzheimer's disease, tacrine, it seems appropriate to reappraise the pharmacological processes of innovation in the field of research in dementia. The aim of this review is to pinpoint concrete improvements achieved in this field, in terms of experimental methods and clinical evaluation of the compounds, as well as the neurochemistry of the disease and cellular targets deserving of initial consideration. * The article first considers the use of animal models of Alzheimer's disease, which are classified according to two categories: animals with lesions of some neuronal pathways specifically implicated in clinical symptoms (i.

Pharmacology of Alzheimer's disease: appraisal and prospects.

Ten years after the introduction of the first drug, tacrine, in the treatment of Alzheimer's disease, it seems appropriate to re-appraise the pharmacological processes of innovation in the research field of dementia. The aim of this review is to pinpoint concrete improvements achieved in this field, regarding experimental methods and clinical evaluation of the compounds, as well as the neurochemistry of the disease and cellular targets to consider in priority. This review deals with this objective in three parts: (1) assessment of current therapeutics, (2) discussion of the experimental models and clinical practices and (3) prospective drugs of the future.

Milnacipran: an antidepressant with dual selectivity of action on noradrenaline and serotonin uptake.

Milnacipran is a new antidepressant which possesses potent and doubly selective action in that it inhibits both the re-uptake of serotonin and noradrenaline without any effect on other neurotransmitter systems. The almost equipotent inhibition of serotonin and noradrenaline by milnacipran is functionally reflected in the several-fold and long-lasting increase of the levels of these monoamines in the brain and in antidepressant-like effects in animals. In man, milnacipran distinguishes itself from many other antidepressants by its simple pharmacokinetics.

Undesirable blood pressure changes under naturalistic treatment with moclobemide, a reversible MAO-A inhibitor--results of the drug utilization observation studies.

Blood pressure decrease, associated with postural hypotension, as well as spontaneous hypertension are considered to be typical side-effects of conventional, irreversible and nonselective MAO (A+B) inhibitors. The new generation of reversible MAO-A inhibitors is, however, expected to have negligible cardiovascular effects and low propensity to induce either blood pressure increases or decreases. But, the true incidence of such changes is largely unknown since observation studies, specifically assessing the frequency of blood pressure changes, in unselected population of patients treated in the practice, are lacking.

Fluoxetine versus moclobemide: cross-comparison between the time courses of improvement.

Competitive statistical methods were used in a meta-analysis of the data of 440 fluoxetine-treated and 437 moclobemide-treated patients in order to address the issue of the timing of recovery from depression, and to elucidate potential differences in the onset of action between the two different classes of antidepressants. In spite of large biochemical and pharmacological differences, fluoxetine and moclobemide turned out to be virtually identical with regard to the overall efficacy, proportions and time characteristics of premature withdrawal, and most notably, the time course of recovery. The onset of improvement occurred in the majority of cases within the first two weeks of treatment and was highly predictive for the outcome after six weeks.

Assessment of sexual dysfunction in depressed patients and reporting attitudes in routine daily practice: Results of the postmarketing observational studies with moclobemide, a reversible MAO-A inhibitor.

Object: The aim of this study was to assess the effect of moclobemide on sexual dysfunction in depressed patients treated under routine conditions in private practice and hospital settings.

Method: sexual function was systematically assessed by a specific questionnaire and by recording spontaneously reported adverse events during large prospective postmarketing surveillance studies with moclobemide, carried out in Germany between 1992 and 1995. The data of 4333 patients were collected in two different settings: (a) specialized psychiatric and neurological private practices and (b) psychiatric hospitals.

Onset of improvement under fluoxetine and moclobemide.

In a meta-analysis of the selective serotonin reuptake inhibitor fluoxetine (n = 440) and the reversible and selective monoamine oxidase-A inhibitor moclobemide (n = 437) we investigated the time course of improvement over 6 weeks for these two classes of anti-depressants. Two different methods of approach were applied: (1) repeated measurement analysis of variance in combination with regression analysis, and (2) a survival-analytical approach that allowed us to determine onset of improvement for the individual patient, to distinguish between early and late improvers, to assess the predictive value of early improvement, and to adequately process premature withdrawals. The two antidepressants of large biochemical and pharmacological differences yielded virtually identical response- and drop-out rates, and exhibited no difference with respect to the time course of improvement.

Delayed onset of action of antidepressant drugs? Survey of recent results.

The onset of action of antidepressant drugs was investigated on the basis of two independent multicenter, double-blind efficacy studies comparing amitriptyline (n = 120), oxaprotiline (n = 120), imipramine (n = 506) and moclobemide (n = 580) with placebo (n = 189 + 191). The samples consisted of in- and outpatients diagnosed, according to Diagnostic and Statistical Manual (DSM)-III criteria, as suffering from major depressive disorder. Measures of efficacy criteria were the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A) and the Zung Self-Rating Depression scale.

Onset of action under antidepressant treatment.

The issues of timing in antidepressant treatment are of great theoretical and practical relevance, even more so since recent meta-analyses yielded no evidence for a specific mode of action of antidepressants, which, according to the theory of delayed onset of action, is expected to emerge after 2 weeks of therapy. To address the issues of timing on a methodologically sound basis, future trials should adapt a 'longitudinal' rather than 'cross-sectional' design, standardized with respect to a washout period, baseline and first 2 week assessments. With this in mind, special attention should be paid to parameters which potentially enable the identification of placebo responders, true drug responders and patients at risk of non-improvement.

Moclobemide versus fluoxetine for double depression: a randomized double-blind study.

The efficacy and tolerability of the selective reversible monoamine oxidase A inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor, fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind fixed-dose study in patients (n = 42) with double depression (DSM-III-R: dysthymia with superimposed major depressive episode) using weekly assessment on the Hamilton depression rating scale (HDRS-17 items) and clinical global impression (CGI) scale. The primary efficacy outcome measure was a decrease > or = 50% in end of treatment HDRS score, secondary measures were the mean total endpoint HDRS scores and percentages of CGI very good and good responses. Tolerability was measured by the frequency and severity of volunteered adverse events.

Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia--a study group report.

The results of an open tolerability and exploratory efficacy study of bretazenil, a partial benzodiazepine-receptor agonist in hospitalized schizophrenic patients with an acute psychotic episode (DSM-III-R criteria), are presented. The duration of the study was 6 weeks, with a mandatory titration (ascending doses of 3-18 mg/day) period of 14 days. The assessment criteria for tolerability were the frequency of adverse events (including EPS), vital signs and laboratory tests.

Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses.

The onset of action of antidepressant drugs was investigated on the basis of two independent, multicenter, double-blind studies, comparing amitriptyline (N = 120), oxaprotiline (N = 120), imipramine (N = 506) and moclobemide (N = 580) with placebo (N = 189/+191). Highly significant differences between the active drugs and placebo were found with respect to the total number of improvers and the total number of responders. In addition, significant differences between treatment modalities showed up in both the percentage rate and the time distribution of premature withdrawals.

Antidepressants and drug-metabolizing enzymes--expert group report.

Antidepressant drugs are extensively metabolized. Consequently, the biotransformation pattern of antidepressants has an important influence on their clinical properties, i.e.

Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies.

The results of the meta-analysis of studies comparing the efficacy of moclobemide, imipramine and so-called sedative antidepressants (amitriptyline, mianserin and maprotiline) in 2416 patients are described. The results demonstrated that in agitated-anxious depressive patients (defined by HAMD factor score or HAMD item 9) a nonsedative, reversible MAO-A inhibitor moclobemide has about equal efficacy as imipramine or sedative antidepressants. All antidepressants were clearly superior to placebo, irrespective of the outcome measures applied (> 50% HAMD decrease, CGI improvement).

Benzodiazepines and GABA hypothesis of schizophrenia.

Clinical and experimental studies pertinent for demonstrating the antipsychotic potential of benzodiazepines (BDZ) and the involvement of γ-aminobutyric acid (GABA) in the origin of schizophrenia are reviewed. It is shown that, due to severe methodological problems and pitfalls, placebo-controlled, double-blind studies do not permit unequivocal conclusions on the efficacy of BDZs, but neither do they completely disprove it. Furthermore, at first glance, confusing and controversial findings in animal models indicate a bi-directionality of effects of full BDZ agonists on dopamine-mediated functions, which may perhaps be explained by (i) anatomical and functional organization of the GABA-dopamine system in the nigro-striatal and ventro tegmental area, and (ii) the regional non-selectivity of action of these drugs.