flupenthixol-decanoate and Dyskinesia--Drug-Induced

There are no data available on the risk of extrapyramidal symptoms when using long-term flupenthixol in low dosage in patients suffering from anxiety and depressive disorders. In a case control study 106 patients essentially treated with the neuroleptic flupenthixol in a so-called low, non-antipsychotic dosage were compared to n=37 otherwise comparable patients who never had been treated with neuroleptics. The investigator was blind to the previous treatment conditions. Extrapyramidal symptoms were found although with a low prevalence and mild degree: 6.7% tardive dyskinesia, none in controls; pseudoparkinsonism 26%, 16% in controls. Extrapyramidal side-effects, especially tardive dyskinesia, have to be considered in the individual weighing of therapeutic benefits and risks even when prescribing flupenthixol in low dosages.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Case-Control Studies; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Flupenthixol; Germany; Humans; Male; Middle Aged; Parkinson Disease, Secondary

Attitude towards treatment, side-effects, mental state and quality of life was assessed in 53 chronic schizophrenic out-patients on maintenance treatment with depot neuroleptics. It was found that 60% of the patients viewed depot medication positively, while only 8% viewed it negatively. Only 70% of patients complained about side-effects, even though 94% had scored as having them. Hypokinesia and hyperkinesis were the side-effects least noticed by the patients, but most noticed by the treating physician, while the opposite was the case with psychic side-effects. Only 49% of patients thought they had a psychotic illness, and there was no correlation between the patients' own evaluation of the severity of their illness and their score on the Positive and Negative Symptom Scale (PANSS) or the treating physician's evaluation. Quality of life did not correlate with either side-effect score or PANSS score. The schizophrenic patients' assessment of their condition was therefore in general different both from that of the treating physician and from that determined using rating scales.

Topics: Adult; Aged; Antipsychotic Agents; Chronic Disease; Clopenthixol; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Flupenthixol; Humans; Male; Middle Aged; Neurologic Examination; Perphenazine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Sick Role

Topics: Adult; Alcoholism; Bipolar Disorder; Diagnosis, Dual (Psychiatry); Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Flupenthixol; Humans; Neurologic Examination; Psychoses, Alcoholic; Recurrence; Substance Withdrawal Syndrome; Tranquilizing Agents

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

Topics: Administration, Oral; Antipsychotic Agents; Chronic Disease; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Injections, Intramuscular; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology

The development of vacuous chewing movements (VCMs), and changes in glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) activities in extrapyramidal nuclei were examined in rats treated chronically with neuroleptics. Animals were injected with flupenthixol (FLU) or haloperidol (HAL) decanoate for 16, 40 or 48 weeks and were then sacrificed. Another group of rats was treated with FLU or HAL for 48 weeks, and then withdrawn from the neuroleptics for 16 weeks before sacrifice. VCMs were assessed weekly, and the effects of the GABA agonist progabide on VCMs and locomotor activity were examined. GAD and ChAT activities were determined at death. The concentrations of Calbindin D28K (CaBP) and parvalbumin (PV) were determined in rats receiving 48 weeks of neuroleptic treatment. VCMs first appeared after 8-10 weeks of neuroleptic administration, reached asymptotic rates after 18-20 weeks, and then remained stable for the remainder of the chronic drug administration period. During withdrawal, there was a steady decline in the VCM rate. The GABA receptor agonist progabide reduced VCMs and locomotor activity. Significant decreases in nigral GAD activity were observed after 40, but not after either 16 or 48 weeks of neuroleptic administration. CaBP and PV were unchanged after 48 weeks of neuroleptic treatment. In addition, ChAT activities in 16, 40 or 48 week treated animals did not show consistent changes after either neuroleptic. Chronic neuroleptic administration followed by 16 weeks of withdrawal also did not have any significant effects on GAD or ChAT activity in any of the brain areas examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Brain; Choline O-Acetyltransferase; Dyskinesia, Drug-Induced; Flupenthixol; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Haloperidol; Male; Mastication; Motor Activity; Parvalbumins; Rats; Rats, Inbred Strains; S100 Calcium Binding Protein G

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Male; Prognosis; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Humans; Middle Aged; Psychotic Disorders; Schizophrenia

Attempting to improve long-term neuroleptic treatment of schizophrenic patients several injectable depot neuroleptics have been developed. Moreover pharmacokinetic data increasingly have been clinically applied. On this background the purpose of the present paper has been to make an updated review of the clinical and pharmacokinetic knowledge of depot neuroleptic treatment. First, general aspects of antipsychotics have been summarized, and an outline of methodological questions relevant to clinical-pharmacological trials are given. Subsequently general aspects including pros & cons of depot administration are examined. Finally the available data of the various depot preparations have been scrutinized. It is concluded that our present pharmacokinetic knowledge of the particular preparations is incomplete. Thus more information of clinical relevant aspects are needed, e.g., the existence of a therapeutic range, maximum/minimum concentration ratio, and the significance of active metabolites. Comparing the various depot neuroleptics, no significant differences are seen regarding the clinical effects. However, the decanoate esters seem clinical superior to the corresponding enanthate esters explained by the more flat concentration curve of the decanoates. Apart from that, a comparison of the pharmacokinetic data is difficult because of the heterogenecy of the available data. Haloperidol, clopenthixol and perphenazine decanoates are among the best examined preparations in pharmacokinetic respects. A controlled double-blind comparative study of these preparations would be of interest.

Topics: Administration, Oral; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Flupenthixol; Fluphenazine; Haloperidol; Humans; Kinetics; Long-Term Care; Patient Compliance; Perphenazine; Schizophrenia; Schizophrenic Psychology; Thiazines

Topics: Adult; Antipsychotic Agents; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Flupenthixol; Fluphenazine; Humans; Long-Term Care; Male; Schizophrenia, Paranoid; Torticollis