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Matthias J Müller

Publications and source records attributed to Matthias J Müller.

31 records · Page 2Linked to original sources
PubMed2004

Therapeutic monitoring of new antipsychotic drugs.

Typical antipsychotic drugs qualify for therapeutic drug monitoring (TDM) primarily for the following reasons: control of compliance and avoidance of extrapyramidal side effects by keeping chronic exposure to minimal effective blood levels. For the atypical antipsychotic clozapine, drug safety is another reason to use TDM. With regard to the new antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole, which have been introduced in the clinic during the last few years, the rationale to use TDM is a matter of debate. Positron emission tomography (PET), which enables measurement of the occupancy of dopamine D2 receptors, revealed that receptor occupancy correlated better with plasma concentrations than with doses of the antipsychotics. Regarding plasma levels related to therapeutic effects, optimal concentrations have been established for clozapine (350-600 ng/mL), risperidone (20-60 ng/mL), and olanzapine (20-80 ng/mL) but not for the other new antipsychotics. Studies that included analyses of drug levels in blood reported mean concentrations of 68 ng/mL for quetiapine and 317 ng/mL for amisulpride under therapeutic doses of the antipsychotic drugs. For ziprasidone or aripriprazole, data on therapeutic drug concentrations are so far lacking. In conclusion, evidence is growing that TDM may improve efficacy and safety in patients treated with the new antipsychotic drugs, especially when patients do not respond or develop side effects under therapeutic doses. The few reported investigations, however, need to be confirmed and extended.

Antipsychotic Agents↗
PubMed2004

Combination treatment with nefazodone and cognitive-behavioral therapy for relapse prevention in alcohol-dependent men: a randomized controlled study.

BACKGROUND: This study evaluated the serotonergic antidepressant nefazodone versus placebo and specific cognitive-behavioral therapy (CBT) versus nondirective group counseling (GC) for relapse prevention in alcohol dependence in a large prospective, randomized, and placebo-controlled double-blind study at 3 German university centers. METHOD: 242 male patients fulfilling at least 5 criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible, after detoxification, for one of the following treatment combinations: nefazodone + CBT, nefazodone + GC, placebo + CBT, and placebo + GC. Either nefazodone or placebo was administered throughout the evaluation period of 15 months. Either CBT or GC was applied during the first 12 weeks as group therapy according to operationalized manuals. The main outcome measures (assessed at 3 and 12 months of treatment) were the cumulative number of abstinent days, the amount of ethanol consumed during specified evaluation periods of 3 and 12 months, the number of relapses, and the duration of time until first relapse. RESULTS: After 12 weeks of treatment, no statistically significant differences were observed between the 4 treatment combinations in any outcome measure. After 52 weeks, the only significant difference was observed in the amount of ethanol consumed, with the nefazodone + GC group showing higher alcohol intake than the other 3 groups. CONCLUSIONS: The results from this carefully designed clinical trial suggest that the 4 treatment combinations do not differ substantially in their efficacy for relapse prevention in nondepressed, severely alcohol-dependent patients. Nefazodone might even increase the risk of consuming a larger amount of ethanol per relapse in a subset of patients. CBT as performed in this study was associated with little additional benefit compared with structured GC.

Adult↗
PubMed2003

Distigmine bromide induced acute psychotic disorder in a patient with multiple sclerosis.

A female patient with multiple sclerosis (MS) suffered from an acute psychotic disorder after taking distigmine bromide for detrusor dysfunction. She showed a dramatic relief of her symptoms after the medication, distigmine bromide, was stopped. Distigmine is not supposed to penetrate the blood-brain barrier (BBB). However, in MS patients a leakage of the BBB could be hypothesized.

Female↗
PubMed2003

Standardized rater training for the Hamilton Depression Rating Scale (HAMD-17) in psychiatric novices.

BACKGROUND: Despite the long and widespread use of the Hamilton Depression Rating Scale (HAMD), standardized reliability studies in inexperienced raters are not available. METHODS: Rater training was carried using three videotaped interviews with depressed patients in 21 psychiatric novices who had negligible previous experience with the HAMD. Chance-corrected coefficients of rating agreement with expert standards (weighted kappa, ICC) were computed for single items and the total score of the HAMD. RESULTS: The results demonstrate sufficiently high interrater reliability (kappa>0.60) for most of the HAMD items and the total score (ICC=0.57-0.73). Three standardized HAMD training sessions seem adequate to establish satisfactory agreement among psychiatric novices. LIMITATIONS: The sample of video-taped interviews and, hence, the generalizability of the results, was restricted. CONCLUSIONS: High inter-rater reliability of the HAMD justifies the use by clinically inexperienced researchers after standardized training.

Adult↗
PubMed2003

Differentiating moderate and severe depression using the Montgomery-Asberg depression rating scale (MADRS).

BACKGROUND: MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale (HAMD(17)) and the Clinical Global Impressions Scale (CGI). METHOD: HAMD(17), MADRS, and CGI ratings from patients with major depression (DSM-IV) were analyzed (N=85). Receiver operating characteristics (ROC) curves were applied. RESULTS: Mean age was 51.4+/-14.5 years, 69% were female. Mean MADRS scores were 23.4+/-13.2, HAMD(17), MADRS, and CGI scores were highly correlated (r>0.85; P<0.0001). Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 (sensitivity 93.5%, specificity 83.3%). LIMITATIONS: Studies to validate severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended. CONCLUSIONS: Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17) and CGI severity ratings in patients with major depression were yielded.

Adult↗
PubMed2003

Symptom-triggered versus standard chlormethiazole treatment of inpatient alcohol withdrawal: clinical implications from a chart analysis.

To evaluate clinical effectiveness and safety of 2 different detoxification treatment protocols, a chart analysis of hospital inpatients consecutively admitted for alcohol withdrawal during one year was undertaken. Records of 33 patients receiving symptom-triggered treatment (using a modified version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale) were compared with those of patients treated by applying a fixed-dose regimen (n = 32). Patients (45.3 +/- 9.8 years, 21% female) of both groups were comparable regarding illness severity, epidemiologic parameters as well as complications during the observed treatment period. Under symptom-triggered therapy, chlormethiazole (CMZ) treatment duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann-Whitney U test: p = 0.0003) and cumulative CMZ dosage (4352 +/- 4589 vs. 9921 +/- 6599 mg, Mann-Whitney U test: p = 0.0004) were significantly reduced. The daily CMZ dose was significantly lower at days 1-5 in the group receiving symptom-triggered treatment. There was no influence of age on the outcome parameters of either treatment group. In conclusion, an individualized symptom-triggered treatment of alcohol withdrawal with CMZ seems to be equally safe but more efficient than a scheduled regimen.

Adult↗
PubMed2003

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.

Adolescent↗
PubMed2002

Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo.

The antipsychotic effect of neuroleptics cannot be attributed entirely to acute blockade of postsynaptic D(2)-like dopamine (DA) receptors, but may arise in conjunction with the delayed depolarization block of the presynaptic neurons and reduced DA synthesis capacity. Whereas the phenomenon of depolarization block is well established in animals, it is unknown if a similar phenomenon occurs in humans treated with neuroleptics. We hypothesized that haloperidol treatment should result in decreased DA synthesis capacity. We used 6-[(18)F]fluoro-L-dopa (FDOPA) and positron emission tomography (PET) in conjunction with compartmental modeling to measure the relative activity of DOPA decarboxylase (DDC) (k(D)(3), min(-1)) in the brain of nine unmedicated patients with schizophrenia, first in the untreated condition and again after treatment with haloperidol. Patients were administered psychometric rating scales at baseline and after treatment. Consistent with our hypothesis, there was a 25% decrease in the magnitude of k(D)(3) in both caudate and putamen following 5 weeks of haloperidol therapy. In addition, the magnitudes of k(D)(3) in cerebral cortex and thalamus were also decreased. Psychopathology as measured with standard rating scales improved significantly in all patients. The decrease of k(D)(3) in the thalamus was highly significantly correlated with the improvement of negative symptoms. Subchronic treatment with haloperidol decreased the activity of DDC in the brain of patients with schizophrenia. This observation is consistent with the hypothesis that the antipsychotic effect of chronic neuroleptic treatment is associated with a decrease in DA synthesis, reflecting a depolarization block of presynaptic DA neurons. We link an alteration in cerebral catecholamine metabolism in human brain with the therapeutic action of neuroleptic medication.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

Effects of interrater reliability of psychopathologic assessment on power and sample size calculations in clinical trials.

Although rater training is increasingly used to improve the quality of the investigated outcome parameters, the reliability of assessments is not perfect. Thus, empirical reliability estimates should be used instead of theoretically assumed perfect reliability. Implications of the reliability of psychiatric assessments for sample size and power calculations in clinical trials are presented. The theoretical basis of sample size and power calculations using empirical reliability scores is delineated. Examples from contemporary research on schizophrenia and depression are used to illustrate several implications for study design and interpretation of results. The tremendous impact of the lack of reliability of psychopathologic assessments on sample size, power, and detectable true score differences in clinical trials is shown. The problem of multiple outcome variables with different reliabilities is addressed. Studies lacking power because of unreliable assessments carry the risk of false-negative findings and raise ethical questions. Rater training is strongly recommended to assess and improve interrater reliability whenever necessary and possible before trials are started. Sample size calculations and power analysis should be based on empirical reliability values of outcome parameters as part of quality assurance and cost savings.

Clinical Trials as Topic↗
PubMed2002

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.

Adolescent↗