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Biomedical subjects

L G Schmidt

Publications and source records attributed to L G Schmidt.

At least 91 records · Page 5Linked to original sources

[Pathobiochemistry and pharmacotherapy of alcohol withdrawal delirium].

The spectrum and time course of different symptoms during alcohol withdrawal may be caused by the involvement of various neurotransmitter systems that are differentially vulnerable to the effects of ethanol. Withdrawal symptomatology results from increased activity of excitatory mechanisms (NMDA-receptor, catecholamines among others) and from reduced functioning of inhibitory receptors (GABAA-, alpha 2-adreno-receptor among others). The neuronal mechanisms are subject to different dynamics of restitution following intoxication. Some of these probably contribute to long-lasting changes in CNS functions by "kindling" processes. Therapeutic guidelines are deduced from results of basic research and clinical trials. It is concluded that clomethiazole and benzodiazepines are superior in treating delirium tremens and certain risk-patients, whereas carbamazepine and clonidine may be helpful in moderate withdrawal syndromes or as adjunctive agents. However, the need for improved methodological standards of method in clinical research is evident.

Alcohol Withdrawal Delirium↗

Extrapyramidal symptoms in neuroleptic recipients.

Adverse drug reactions (ADRs) in psychiatric therapy were continuously assessed in the AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie (drug surveillance in psychiatry] conducted at two psychiatric university departments in the F.R.G. The Intensive Drug Monitoring (IDM) method was used to monitor 1107 patients, 754 of whom received neuroleptics (NLs). As is the rule in clinical psychiatric practice, polypharmacy was frequent, with combinations of two neuroleptics and combinations of a neuroleptic and an antiparkinson drug ranking first and second, respectively. Extrapyramidal motor symptoms (EPMS) were observed in 35% of the NL patients. In most cases they required a change in medication, usually addition of an antiparkinson drug. In about one quarter of all EPMS cases, withdrawal of the imputed NL was necessary. Parkinsonism was the most frequent single symptom, followed by acute dystonia and akathisia. Differences in EPMS rates between the two most frequently used neuroleptics, haloperidol, a high-potency butyrophenone, and perazine, a medium-potency phenothiazine, were distinct. EPMS were observed with haloperidol in 56% and attributed to haloperidol alone in 92% of these cases. With perazine, an EMPS occurred at a rate of only 14%, and in 37% of the cases EMPS were attributable to perazine in combination with other NLs. Age, sex, diagnosis and dosage of administered NLs were closely interrelated. For instance, NL patients over 60 years of age were almost exclusively female, the majority of them being endogenous depressives, whereas in younger patients the diagnosis of schizophrenia prevailed. Therefore, analysis of potential risk factors for development of EPMS must simultaneously include diagnosis, sex and age as well as concomitant physical disease, duration and dosage of all drugs administered before development of EPMS. However, the small case numbers in some subgroups, as we found them in this study based on everyday clinical practice, will probably be a limiting factor in such multivariate analyses.

Acute Disease↗

Adverse effects of clozapine.

Adverse effects related to clozapine were assessed within a post-marketing drug surveillance program, the AMUP study, in two university psychiatric departments. In a randomly selected sample of patients (intensive drug monitoring) ADRs of any type were observed in 76% of clozapine-treated inpatients. Sedation, hypersalivation, increase in transaminases, and EEG changes were most frequently observed, but only rarely required changes in therapy. In 8.1% of 959 patients exposed to clozapine in the total inpatient population of the participating hospitals ADR led to withdrawal of clozapine; in 3.9% reactions judged as severe and potentially life-threatening occurred. Among these latter toxic delirium prevailed. In addition, four cases of severe cardiovascular and respiratory dysregulation were observed with the combination of clozapine and benzodiazepines. These cases and one case of sudden death under clozapine and haloperidol treatment are presented in some detail. The results obtained for clozapine are compared to data from this drug surveillance program for other neuroleptics.

Adult↗

Agranulocytosis and significant leucopenia with neuroleptic drugs: results from the AMUP program.

In the Federal Republic of Germany adverse drug reactions (ADR) have been continuously assessed at the departments of Psychiatry of Berlin and Munich since May 1979. About 13,000 neuroleptic-treated inpatients were monitored until August 1988. Approximately 1100 patients were exposed to clozapine, 6800 to haloperidol and 6000 to perazine, the two most frequently used neuroleptic drugs. In this 9-year period seven cases of agranulocytosis were observed, all in women. One case occurred with clozapine in monotherapy, the other six with perazine, three times in monotherapy, once in combination with trimethoprim/sulfamethoxazole and in one case each in combination with tricyclic antidepressants. Significant leucopenia (less than or equal to 3000/mm3) was observed in an additional eight cases. On four occasions each butyrophenones (twice in combination with TCA) and tricyclic neuroleptics (once in combination with TMS) were involved. The number of exposed patients per drug is too small for calculation of statistically valid incidence rates, especially in view of the frequent polypharmacy. The course of agranulocytosis was benign in all seven cases and required no other treatment than drug withdrawal in three cases. The early detection by regular WBCs is supposed to be mainly responsible for this and is therefore recommended at weekly intervals. This measure of safety appears most important for all medium potency tricyclic neuroleptics. As to treatment of agranulocytosis, additional measures (antibiotics, intensive medical care) depend upon the severity of the clinical picture.

Adult↗

Utilization and safety of fluspirilene in nonpsychotic outpatients.

Over a six-month period, the utilization and safety of fluspirilene were investigated in 230 nonpsychotic outpatients in twelve private psychiatric practices. The patients treated under routine treatment conditions were about 20 years older than those included in experimental studies with this drug. In contrast to expert recommendations, 21.7% of the patients had received repeated injections of fluspirilene for longer than three months. A total of 46.1% of patients had been comedicated from time to time with antidepressants, while 30% had received benzodiazepines, indicating that fluspirilene is used as an alternative, but also as a supplementary treatment to benzodiazepine tranquilizers. Adverse reactions, probably related to fluspirilene, were recorded in 8.7% of patients and led to discontinuation of treatment in 3.9%. Disturbances of the extrapyramidal system predominated (in 5.6% of patients), with akathisia being observed most often (in 3.5%). It is concluded that the application of fluspirilene would seem to be safe if the drug is administered in the recommended way, but that there is a risk of tardive dyskinesias in the case of higher doses, longer duration of use, or pre-existing cerebral lesions (as manifested by two patients included in this survey).

Adolescent↗

Prevalence of benzodiazepine abuse and dependence in psychiatric in-patients with different nosology. An assessment of hospital-based drug surveillance data.

Frequencies of abuse and dependence assessed continuously within a drug surveillance system were analysed as a contribution to risk-benefit evaluations of benzodiazepines (BZDs). In 4.7% of 15,296 patients admitted to psychiatric hospitals between 1980 and 1985, BZDs had been involved in some kind of abuse or dependence. Primary BZD dependence, defined as physical dependence on BZDs in patients who had not been dependent before, was observed in about 1% of admitted patients. Linking these data with psychiatric diagnoses revealed a high risk of primary BZD dependence for in-patients (11.8%) with anxiety neurosis (ICD-9, 300.0), and a lower risk for neurotic (300.4) and for endogenous depressives (296.1) (risk 3.7% and 2.7% respectively). Older age was also related to primary BZD dependence. For depressive in-patients, the risk was twice as high in females as in males. Anecdotal observations advocate more systematic investigation of the emotional effects of long-term therapy with BZDs.

Affective Disorders, Psychotic↗

[Incidence and therapeutic relevance of the adverse effects of antidepressive agents within the scope of ambulatory neurologic treatment].

Within a postmarketing drug surveillance study the incidence and relevance of ADRs leading to drug discontinuation in therapy of depressed outpatients were examined. In addition, corresponding drug prescribing patterns of patients under routine treatment conditions were recorded. It was found that most psychiatric outpatients were able to identify common ADRs and to differentiate them from the underlying illnesses and comedication. Low-dose therapy was confirmed as routine treatment in the majority of psychiatric outpatients. No differences regarding age, sex, and dosage could be found between patients with further drug intake and those who stopped their antidepressant medication because of ADRs. Such events had been recorded in 11.5% of patients with first prescriptions made by the treating physicians in a monitoring of three months. However, only 0.3% of patients on long-term therapy (that had been initiated at treatment terms preceding the monitoring period) experienced an ADR indicating a decreased risk for drug discontinuation (because of ADR) the longer the patient was on treatment. Knowing ADR(-profiles) of prescribed drugs by treating psychiatrist may aid the treatment of compliance or prevention of ADRs.

Antidepressive Agents↗

Recent trends in prescribing psychotropic drugs at a psychiatric university hospital (1981-84).

Analysis of the prescribing of psychotropic drugs in the psychiatric hospital of the Free University of Berlin revealed a slight decrease in the mean number of prescriptions to our patients over recent years. As a response to intensified psychopharmacological pretreatment the proportion of patients who had initially been treated drug-free (up to the 10th day after admission) rose steadily every year. The use of neuroleptics increased significantly, mainly due to increased prescriptions of this group of compounds to endogenous depressives. The use of benzodiazepines, however, decreased in all groups of patients. Simultaneous use of neuroleptics was a clear leader in the category of drug combinations. Low-potent neuroleptics (i.e. perazine, clozapine), clomipramine, and the MAO-inhibitor tranylcypromine were preferred increasingly in recent years; reduced prescription rates were found for haloperidol, clomethiazol, and metamizol. These changes may be related to an ongoing process of reevaluating benefits and risks of available treatments. The systematic updating of prescribing patterns is an essential tool for quality control of psychiatric pharmacotherapy.

Adult↗

[Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report].

Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day-clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment.

Adult↗

[Benzodiazepines and barbiturates in chronic alcoholics and opiate addicts. An epidemiological study of hospitalized addicts].

In a prospective study of 282 chronic alcoholics and 67 opiate addicts, frequency and pattern of drug intake were determined by questioning and urinalysis on admission to a special unit of a psychiatric hospital. 20.2% of alcoholics and 44.8% of opiate addicts stated that they had taken psychotropic drugs before admission, women in both groups naming such drugs significantly more frequently than men. But taking into account results of urinalysis, 25.5% of alcoholics and 31.3% of opiate addicts were found to have taken benzodiazepines before hospital admission. 41.8% of opiate addicts either stated or were found to have taken barbiturates. High dosages of benzodiazepines were found in those alcoholics who had mentioned taking them. Thus in practice the treatment of addicts differs markedly from recommendations made by well-known experts. There is also a need to improve the clinical diagnosis and treatment of addicts.

Adult↗

Longitudinal assessment of psychotropic drug use in acutely-ill psychiatric inpatients.

Psychotropic drug surveys serve to provide retrospective control of actual treatment conditions in psychiatric hospitals. Data of overall drug consumptions and those indicating the time pattern of medication were recorded at 7 census days for 1,415 inpatients of the psychiatric hospital of the Free University of Berlin. Drug-treated patients with 3.15 different psychotropic drugs on average during their stay. Neuroleptics were the most chosen compound group with regard to all patients treated (62.2%), the number of prescriptions (48.3%) and the sum of psychotropic days (57.9%). Sedatives (i.e. benzodiazepines and chloralhydrate) were given to more patients than antidepressants (41.0% vs. 29.3%), but accounted for only 5.7% of all psychotropic drug days (21.4% in case of antidepressants). The analysis of time pattern revealed that the prescription of neuroleptics was favoured on all census days, while prescribing for antiparkinsonian and lithium drugs increased also over time, but not for sedatives. Mean daily doses of most neuroleptics peaked near the 10th day after the patients' admission, while those of antidepressants increased steadily until the patients were discharged. Monotherapy was found in 59.0%, drug combinations in 41.0% of prescriptions (on all census days). The proportion of drug combinations in relation to monotherapy increased the longer the patients were in hospital. Among all drug combinations, two drugs had been combined in 79.2%, three or more in 20.8%. Two or more neuroleptics given simultaneously were involved in 44.9% of all combinations--an unexpected finding calling for more systematic investigation.

Adult↗

Consistency of assessment of adverse drug reactions in psychiatric hospitals: a comparison of an algorithmic and an empirical approach.

Within an ongoing drug surveillance project (AMUP) in psychiatric hospitals, a comparative study was carried out to evaluate two methods commonly used in the field of adverse drug reaction assessment. Two raters, who have cooperated with the project since its inception, evaluated 80 randomly selected ADRs twice; first, by an empirical (implicit) approach, and second, 4 weeks later, by using an algorithm as proposed by Kramer et al. 1979. Agreement on medication and related probability ratings was obtained in 81% of all 80 cases for the empirical method (weighted Kappa = 0.41), and in 69% for the algorithmic method (weighted Kappa = 0.62), indicating that agreement exceeded chance for both methods. By comparison with assessments made in previous case conferences of the project, empirical ratings were found to be reliable over time due to homogeneous use of criteria by project raters. In contrast to the reports on the subject, agreement between raters appeared to be superior in the empirical method as compared to the algorithmic assessment. Analysis of disagreements suggested that probability ratings based on the empirical method were nonspecific, due to conventional criteria applied in the project. Inter-rater agreement was reduced by polypharmacy, especially in the case of algorithmic assessments. The consistency of assessment was also lowered by the fact that the 2 methods assigned different weights to particular assessment criteria.

Drug-Related Side Effects and Adverse Reactions↗