Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.

This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties.

Sleep investigations in erectile dysfunction.

Regarding the aetiology of erectile dysfunction, beside numerous organic causes in many cases psychological factors play an important role. The pathophysiological mechanisms underlying the so-called psychogenic erectile dysfunction are not yet understood. Based on a neurobiological approach to psychogenic erectile dysfunction, polysomnographic investigations were carried out with the aim of identifying possible alterations of the sleep EEG. 24 male patients with psychogenic erectile dysfunction without detectable organic factors or other mental disorders were studied in the sleep laboratory, as well as an age-matched control group without sexual dysfunctions. Beside a reduction of sleep efficacy, the most prominent finding was a shortening of REM latency in the patients compared to the controls. Moreover, spectral analysis revealed a reduced theta power for all sleep stages and a reduced delta power for stage II and slow wave sleep in the patients. The findings support the point of view that psychogenic erectile dysfunction is an organic disorder of the brain. The sleep EEG abnormalities may reflect dysregulations in limbic structures which are suggested to be involved in the pathophysiology of sexual dysfunctions. As these alterations had also been reported for other mental disorders, particularly depression, they appear to be non-specific biological abnormalities for different psychiatric syndromes, including psychogenic erectile dysfunction.

Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression.

OBJECTIVE: Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission. METHOD: We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course. CONCLUSION: Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.

Syndrome profiles in alcoholism and panic disorder with or without agoraphobia: an explorative family study.

It is proposed that alcoholism and panic disorder/agoraphobia demonstrate in part common genetic and environmental origins. Shared subthreshold symptom patterns in the parents' generation could confirm the proposed genetic role in alcoholism and panic disorder/agoraphobia, even if the parents do not fulfil the diagnostic criteria for a primary psychiatric diagnosis. This is the first family study of exploratively analyzing subthreshold symptoms in both disorders. The authors investigated families with panic disorder/agoraphobia and/or alcoholism with the Munich-Composite International Diagnostic Interview (M-CIDI). We documented the diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and subdivided the answers of the probands into 16 subthreshold diagnostic groups comprising 259 single items. We found statistically significant correlations of subthreshold syndrome profiles in the parents of patients with panic disorder/agoraphobia and alcoholism. The presented method of analyzing syndrome profiles in a family study seems to be a possibility to demonstrate references to genetic links between patients and parents in anxiety- and alcohol-related disorders.

Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia.

The present analysis investigated symptom-specific dose-response relationships of the atypical antipsychotic amisulpride (AMI) in schizophrenic patients. The effects of different AMI doses on five different symptom dimensions of the Brief Psychiatric Rating Scale (BPRS) were analyzed. Results on global efficacy and safety parameters have been previously published. Four AMI doses (100 mg/day [AMI100], 400 mg/day [AMI400], 800 mg/day [AMI800], 1200 mg/day) were compared with 16 mg haloperidol (HAL16) in a multicenter, double-blind, randomized, parallel-group, 4-week trial. A total of 319 patients with acute exacerbation of schizophrenia (DSM-III-R) were included. AMI100 was compared with the other AMI doses, and HAL16 was compared with all AMI dosage groups. Response on BPRS factors defined as > or = 40% improvement and ORs were computed. An optimal AMI dose was calculated for each BPRS factor based on linear and quadratic regression. For all BPRS factors, inverted u-shaped dose-response curves emerged (r2 > 95%). The estimated AMI dose optimum for the BPRS factors activation/ agitation (760 mg), thought disturbances (716 mg), and hostility/suspiciousness (694 mg) was higher than that for anergia/negative symptoms (584 mg) and depression/anxiety (672 mg). Significant differences (p < 0.05) were found for AMI400/800 versus AMI100 (thought disturbances, hostility/ suspiciousness), for AMI400/800 versus HAL16 (depression/anxiety, thought disturbances, hostility/suspiciousness), and for AMI400 versus HAL16 (anergia/negative symptoms). ORs for response of the BPRS factors depression/anxiety, anergia/negative symptoms, and hostility/suspiciousness were highest under treatment with AMI400 compared to AMI100 and HAL16. For the BPRS factors thought disturbances and activation/agitation, the highest response chance emerged under AMI800 compared to AMI100 or HAL16. AMI seems to show the best clinical efficacy in acutely schizophrenic patients in a moderate dose (400-800 mg/day), with a somewhat lower dose optimum for negative than for positive symptoms. The present finding of distinct dose-response relationships of AMI regarding the BPRS dimensions is in accordance with studies on the mechanism of action of AMI and provides a useful rationale for the clinical treatment of schizophrenic patients with AMI.

Patients' satisfaction with psychiatric treatment: comparison between an open and a closed ward.

The study compared patients' satisfaction with psychiatric inpatient treatment between an open and a closed ward. During a six-month period, all voluntarily participating patients on two wards of a psychiatric University hospital were investigated anonymously at admission and/or before discharge. A self-rating questionnaire (SATQ-98) was used to assess satisfaction with several domains of psychiatric inpatient treatment. In total, 135 questionnaires were received (retrieval rate 49%). The general level of satisfaction with treatment was high. General satisfaction, satisfaction with medication, ward equipment, visiting opportunities, and regulations for going out were significantly lower at discharge on the closed ward. Dissatisfaction with medication was related to low actual mood, and to low satisfaction with the frequency of psychotherapeutic interventions, visiting opportunities, and with the treating doctor. The results thus far strongly support the need for patients' satisfaction with treatment to be taken into account in order to improve psychiatric inpatient services, particularly on closed wards.