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M Dose

Publications and source records attributed to M Dose.

At least 19 recordsLinked to original sources

The N-methyl-D-aspartate antagonist memantine retards progression of Huntington's disease.

According to the excitotoxicity hypothesis, neurotoxicity due to glutamate is regarded as potential factor in the progredient neurodegeneration of Huntington's disease (HD). Memantine, as a glutamate receptor antagonist, should counteract this mechanism. Its effectiveness (up to 30 mg/day) with regard to retardation of progression was thus examined in 27 HD patients in a two year, open and multicentre trial. The results suggest that memantine treatment of HD may be useful in terms of retardation of the progression of the disorder.

Activities of Daily Living↗

[Psychopharmacotherapy of bipolar affective diseases].

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Antidepressive Agents↗

Effectiveness of targeted intervention and maintenance pharmacotherapy in conjunction with family intervention in schizophrenia.

A sample of 85 patients with schizophrenia, of whom 34 later dropped out, received randomised treatment. There were no significant differences between treatment-takers and drop-outs in the variables assessed. Patients received either standard-dose maintenance neuroleptic treatment or targeted maintenance pharmacotherapy and all patients received behavioural family therapy. Measures of psychopathology, social adjustment, side-effects, family burden, and expressed emotion were assessed at baseline and then periodically over an 18-month period. The study was designed to compare the two alternative pharmacological maintenance approaches, each of them supported by psychosocial intervention. Any evaluation of the impact of behavioural family treatment on relapse rates and other outcome criteria is exclusively descriptive. A significantly higher rate of relapse was observed at 18 months in patients randomised to targeted treatment compared to those randomised to standard-dose treatment (35% vs 4%). Although patients assigned to the targeted maintenance group received significantly lower mean doses of neuroleptics, there were no significant differences between the two groups with regard to side-effects, global measures of social function, and overall psychopathology. Family burden was higher in the targeted-treatment group at six months, but did not differ at the one-year and eighteen-month time points. However, both groups improved significantly from baseline to 12 or 18 months in almost all variables assessed. Thus, the behavioural family approach did not compensate for the problems associated with the targeted medication strategy.

Adolescent↗

A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group.

RATIONALE: Studies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are available on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. OBJECTIVE: A 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. METHODS: This study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54-89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. RESULTS: Clinical improvement (> or =20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p<0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p<0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p<0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. CONCLUSIONS: Long-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients.

Adult↗

Abuse potential of anticholinergics.

Anticholinergics are widely used to treat extrapyramidal motor symptoms caused by neuroleptics or other drugs with antidopaminergic (dopamine D2) effects. In the medical literature, occasional reports are concerned with the abuse of centrally acting anticholinergic compounds. These drugs may be abused because of their stimulant effects, mostly by patients on neuroleptic treatment. Their supposed "euphoric" effect when too quickly parenterally administered (only after previous treatment with neuroleptics) seems to consist in the abolition of neuroleptic-induced anhedonia. In a few patients, excessive use of anticholinergics persists in the face of detrimental effects and is, therefore, properly termed "abuse". More commonly, however, patients with schizophrenia take more than the recommended dose of anticholinergics in an attempt to treat the adverse effects of neuroleptics. The abuse of anticholinergics in addicts who are not using neuroleptics is low.

Antipsychotic Agents↗

Recognition and management of acute neuroleptic-induced extrapyramidal motor and mental syndromes.

After nearly 50 years of therapeutic application of neuroleptics, diagnosis and classification of neuroleptic-induced extrapyramidal syndromes still concentrate on their "neurological" (motor) aspects. Psychiatric (mental) aspects are in general - if at all - regarded as "secondary" to motor symptoms. Psychiatric side effects of neuroleptics (including psychotic exacerbations during neuroleptic treatment) have, however, anecdotally been reported since 1954 but never developed into a systematic classification. Accordingly, psychiatric manifestations of extrapyramidal side effects frequently are overlooked, misdiagnosed as psychotic deteriorations and treated by increased dosing of neuroleptics instead anticholinergics, which in addition are falsely suspected of bearing a high addictive potential and the risk of development of tardive dyskinesia. It is suggested that neuroleptic-induced basal ganglia dysfunction results in motor as well as mental extrapyramidal side effects, whose recognition and management is essential to achieve better tolerability of and thereby compliance with neuroleptic treatment.

Acute Disease↗

The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes.

The benzamide derivative tiapride (Tiapridex, Synthelabo) has a highly selective antagonistic effect on striatal adenylate cyclase-independent dopamine-2 receptors. Its in vitro binding affinity is especially high for dopamine receptors which have been sensitized by pre-incubation with dopamine. The involvement of altered dopamine receptor sensitivity in several extrapyramidal dys- and hyperkinesia has been hypothesized. By its high affinity for these receptors, without any affinity for other neurotransmitter receptors of the brain, tiapride is especially well suited for the treatment of movement disorders related to functional dopamine hyperactivity. Even at higher doses, tiapride does not exceed a D2-receptor occupancy of 80%, which is in accordance with the finding that tiapride rarely causes acute extrapyramidal syndromes and has, up to now, never implicated in inducing tardive dyskinesias. On the contrary, clinical studies demonstrate its excellent efficacy in neuroleptic-induced tardive dyskinesia, L-Dopa-induced dyskinesias, psychomotor agitation in geriatric patients and choreatic movement disorders. Since tiapride is not available in the USA as yet, most of the studies concerning tiapride have been carried out in Europe. In a recent study, based on objective measurements, tiapride effectively controlled choreatic movements in patients suffering from Huntington's disease (HD). Tiapride is well tolerated in daily doses between 300 and 1200 mg. Adverse events are generally rare and mild.

Animals↗

Combined treatment of schizophrenic psychoses with haloperidol and valproate.

In accordance with a previous study of adjuvant effects of the anticonvulsant carbamazepine (CBZ) on the neuroleptic treatment of schizophrenic psychoses, the effects of valproate (VPA) were tested in a randomly assigned double-blind, placebo-controlled study. Apart from a (statistically nonsignificant) psychopathological deterioration following discontinuation of VPA while on continuous neuroleptic mediation after four weeks and a statistically significant effect on "hostile belligerence", no overall therapeutic effects of the combination of haloperidol (HPD) with VPA were observed under controlled conditions. Unlike the results with CBZ, concomitant use of VPA led to an even higher consumption of haloperidol and biperiden and to a higher rate of extrapyramidal symptoms compared with the corresponding placebo group, although these differences did not attain statistical significance. In regard to use of the sedative neuroleptic chlorprothixene, there was a trend toward lower doses in the VPA group than in the placebo group. From these results, adjuvant effects like those of carbamazepine in the neuroleptic treatment of schizophrenic psychoses could not be confirmed for valproate in the present study. However, the trend toward lower doses of sedative medication and observed effects on "hostile belligerence" may indicate sedative and/or antimanic properties of valproate which have recently been demonstrated in several controlled studies.

Adult↗

[Huntington disease].

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Adaptation, Psychological↗

Transdermal clonidine for ameliorating post-orchiectomy hot flashes.

To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.

Adult↗

Deliverability of psychoeducational family management.

As part of an open clinical trial currently underway at the Max Planck Institute of Psychiatry in Munich, the feasibility of behavioral family management (Falloon et al. 1984) for schizophrenia in combination with two different neuroleptic medication strategies was investigated. The treatment approaches were psychoeducational family management with a standard dose or with targeted medication. In this article the following questions were addressed: (1) What proportion of the total schizophrenia population admitted as inpatients might be eligible for psychoeducational family treatment (assessment based on n = 411 over a 33-month period)? (2) How representative of this population are the patients who were randomized to the experimental groups? (3) How many patients dropped out of treatment after entering the trial? The results show that about 60 percent (247) of the patients were eligible for a psychoeducational treatment approach. Of these, 34 percent (85) participated in the trial and were randomized to the treatments. Only 4 percent of the relatives but 20 percent of the patients refused to take part in the study. The 85 trial patients did not differ from the total eligible on the numerous socioeconomic and symptom variables assessed. The treatment dropout rate was 11 percent. Those patients who accepted treatment did not differ from those patients who dropped out on socioeconomic or illness variables. The results indicate that early identification of dropouts is not possible at least with the methods used in this study.

Adolescent↗

[Detection of early warning signs in schizophrenic patients. Possible applications in prevention of recurrence].

In the treatment of schizophrenia, two new strategies have been developed with the aim of adequate relapse prevention accompanied by lowest possible risk of side-effects. One strategy is to have the patient continue to take medication at a highly reduced dosage (10-20% of the standard dose). The other is to gradually stop neuroleptic medication after remission and to reinstitute medication only in the case of prodromal symptoms (termed targeted or intermittent treatment). According to Herz and Melville [13] many schizophrenic patients show signs of relapse well before recurrence of overt psychotic features. Monitoring to detect prodromal symptoms is especially important in targeted treatment because, otherwise, neuroleptic medication often cannot be initiated in time. In the present study of 51 schizophrenic patients we were able to replicate the results of Herz & Melville in the German-speaking countries. Prior to acute exacerbation of psychosis, most patients experience alterations of feelings and behaviour. These alterations may also be recognized by family members. Such early warning signs of relapse mainly consist of non-specific, non-psychotic symptoms: tenseness and nervousness, eating less, trouble concentrating and sleeping, depressive mood and seeing friends less. Furthermore, the regular monitoring and use of early warning signs specific to each patient in the aftercare of schizophrenic patients seems to be practicable, especially in psychoeducative family therapy.

Adult↗

[Informed consent requirement in treatment with clozapine according to section 1904 of the patient rights law?].

Clozapine-treatment of schizophrenic psychoses under observation of the producer's directions regarding indication, warnings, information of the patient and control-examinations is no measure which entails (according to section 1904 of German Civil Code-"Betreuungsrecht") the existing risk that the person concerned will die or suffer a serious or lasting health-injury. Therefore, in case of patient's inability to consent, the curator's approval after proper information is regarded to be sufficient in most cases of an intended treatment with clozapine. An approval by the Guardianship Court according to section 1904 should be applied for when--because of medical reasons after evaluating risks and benefits--clozapine-treatment is taken into consideration despite risks and contraindications according to the producer's informations.

Antipsychotic Agents↗

The action of mood-stabilizers in affective disorders: an integrative view as a challenge.

One of the main challenges in the psychopharmacology of affective disorders is to explain the partial similarity of the profiles of action of the different mood-stabilizers lithium, carbamazepine, and valproate, and possibly also calcium antagonists like verapamil and nimodipine. Elucidation of this problem requires understanding the basic neurobiological mechanisms underlying the pathogenesis of affective disorders and would also imply elucidating the modes of action of the different compounds. However, we are far from reaching such an understanding.

Affect↗

Nocturnal sleep in Huntington's disease.

Nocturnal sleep was studied in 16 inpatients with Huntington's disease. In comparison with healthy controls, patients exhibited a disturbed sleep pattern with increased sleep onset latency, reduced sleep efficiency, frequent nocturnal awakenings, more time spent awake and less slow wave sleep. These abnormalities correlated in part with duration of illness, severity of clinical symptoms, and degree of atrophy of the caudate nucleus. Patients showed an increased density of sleep spindles.

Adult↗

Cross-national reliability, concurrent validity, and stability of a brief method for assessing expressed emotion.

The Five-Minute Speech Sample (FMSS; Magana et al., 1986) is a brief method designed to assess the "expressed emotion" (EE) status of a respondent. The FMSS-EE rating is derived from statements made by a patient's key relative during a 5-minute monologue, with codes similar to those used in the original EE rating system (e.g., criticism and emotional overinvolvement). Rating is done from the audiotape and takes about 15-30 minutes. The article reports on the results of a cross-national study carried out in Germany using the FMSS with a sample of 60 relatives of schizophrenic patients. Results indicated that (1) German investigators could readily learn the system and could achieve a high degree of interrater reliability; (2) the association with the original index of EE, the Camberwell Family Interview, was comparable to that found by Magana et al.; and (3) the method yields very stable data over a 4-5 week retest period.

Adolescent↗