flupenthixol-decanoate and haloperidol-decanoate

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.

Topics: Adult; Antipsychotic Agents; Clopenthixol; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Flupenthixol; Fluphenazine; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Movement Disorders; Psychiatric Status Rating Scales; Risperidone; Schizophrenia

Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.

Topics: Adult; Double-Blind Method; Female; Flupenthixol; Haloperidol; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

Stability of neuroleptic medication has been associated with optimal clinical effect and minimal side-effects. Depot administration is assumed to yield better stability.. Thirty patients on depot neuroleptic treatment were followed during three years with repeated measurements of plasma level and concurrent ratings of clinical symptoms and side-effects.. Of 120 blood samples 35 (29%) measurements were outside +/-2 s.d. measurement error (expected 5%). Perphenazine levels were more variable (46%) than haloperidol (25%) and flupenthixol (12.5%). No relationship was found between side-effect ratings and fluctuations of plasma levels.. Depot neuroleptic medication does not eliminate a clinically unwanted and sometimes marked variation in plasma level.

Topics: Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Drug Monitoring; Female; Flupenthixol; Follow-Up Studies; Haloperidol; Humans; Injections, Intramuscular; Long-Term Care; Male; Middle Aged; Neurologic Examination; Perphenazine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

The effect of decanoate forms of flupenthixol and haloperidol on cocaine self-administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability.

Topics: Animals; Cocaine; Flupenthixol; Haloperidol; Injections, Intramuscular; Male; Rats; Rats, Wistar; Reinforcement Schedule; Self Administration; Substance-Related Disorders; Tranquilizing Agents

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