olanzapine and haloperidol-decanoate

The frequency of neuroleptic malignant syndrome (NMS) after clozapine or olanzapine is low and often of non-serious nature. A 49 year-old female patient developed NMS 12 days after olanzapine re-exposure. Olanzapine was stopped, the patient was transferred to an ICU and received a course of nine uni- and bilateral ECT treatments. This led to remission. 14 months earlier the patient had presented with a first severe NMS episode after haloperidol depot injection and 4 days after starting oral clozapine. Following the first NMS episode olanzapine (20 mg per day) was administered for 11 months without adverse effects.

Topics: Antipsychotic Agents; Benzodiazepines; Critical Care; Electroconvulsive Therapy; Female; Haloperidol; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence

Achieving greater continuation of treatment is a key element to improve treatment outcomes in schizophrenia patients. However, reported treatment continuation can differ markedly depending on the study design. In a retrospective setting, treatment continuation remains overall poor among patients using antipsychotics. This study aimed to document the difference in treatment continuation between four long-acting injectable antipsychotics based on the QuintilesIMS LRx databases, national, longitudinal, panel based prescription databases of retail pharmacies, in the Netherlands and Belgium. Paliperidone palmitate once monthly, risperidone microspheres, haloperidol decanoate, and olanzapine pamoate were studied. This study demonstrated significantly higher treatment continuation of paliperidone palmitate once monthly compared to risperidone microspheres (p-value<0,01) and haloperidol decanoate (p-value<0,01) in both countries, a significantly higher treatment continuation of paliperidone palmitate once monthly compared to olanzapine pamoate in the Netherlands (p-value<0,01), and a general trend towards better treatment continuation versus olanzapine pamoate in Belgium. Analysing the subgroup of patients without previous exposure to long-acting antipsychotic treatment revealed the positive impact of previous exposure on treatment continuation with a subsequent long acting treatment. Additionally, the probability of restarting the index therapy was higher among patients treated with paliperidone palmitate once monthly compared to patients treated with risperidone microspheres and haloperidol decanoate. The data source used and the methodology defined ensured for the first time a comparison of treatment continuation in a non-interventional study design for the four long-acting injectable antipsychotics studied.

Topics: Adult; Antipsychotic Agents; Belgium; Benzodiazepines; Delayed-Action Preparations; Drug Administration Schedule; Female; Haloperidol; Humans; Medication Adherence; Netherlands; Olanzapine; Paliperidone Palmitate; Retrospective Studies; Risperidone; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Drug Therapy, Combination; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Schizophrenia

To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden.. A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability.. PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations.. PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost of Illness; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Costs; Female; Haloperidol; Health Care Costs; Hospitalization; Humans; Isoxazoles; Male; Middle Aged; Models, Econometric; Olanzapine; Paliperidone Palmitate; Palmitates; Quality-Adjusted Life Years; Risperidone; Schizophrenia; Sweden

The molecular mechanism of action of antipsychotic drugs is not well understood. Their complex receptor affinity profiles indicate that their action could extend beyond dopamine receptor blockade. Single gene expression studies and high-throughput gene profiling have shown the induction of genes from several molecular classes and functional categories. Using a focused microarray approach, we investigated gene regulation in rat striatum, frontal cortex, and hippocampus after chronic administration of haloperidol or olanzapine. Regulated genes were validated by in situ hybridization, real-time PCR, and immunohistochemistry. Only limited overlap was observed in genes regulated by haloperidol and olanzapine. Both drugs elicited maximal gene regulation in the striatum and least in the hippocampus. Striatal gene induction by haloperidol was predominantly in neurotransmitter signaling, G-protein coupled receptors, and transcription factors. Olanzapine prominently induced retinoic acid and trophic factor signaling genes in the frontal cortex. The data also revealed the induction of several genes that could be targeted in future drug development efforts. The study uncovered the induction of several novel genes, including somatostatin receptors and metabotropic glutamate receptors. The results demonstrating the regulation of multiple receptors and transcription factors suggests that both typical and atypical antipsychotics could possess a complex molecular mechanism of action.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Gene Expression Profiling; Gene Expression Regulation; Haloperidol; Male; Neurotransmitter Agents; Olanzapine; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Signal Transduction; Transcription Factors

The behavioral and neurochemical effects of switching from typical to atypical medications have not been evaluated in the rodent models of tardive dyskinesia. Thus, we treated rats with haloperidol-decanoate for 12 weeks, and assessed the effects of additional treatment with olanzapine, haloperidol, clozapine, or vehicle on vacuous chewing movements and expression of transcripts for dopamine receptors, tyrosine hydroxylase, delta-opioid receptor, prodynorphin, preproenkephalin, glutamic acid decarboxylase-65 (glutamic acid decarboxylase (GAD)-65) and GAD-67 and N-methyl-D-aspartate (NMDA) receptor subunits in the striatum and its efferent pathways. Haloperidol-decanoate induced vacuous chewing movements extinguished following an additional 4 weeks of treatment with vehicle, olanzapine or haloperidol, but not clozapine. Post-treatment, vacuous chewing movements in the clozapine group were significantly higher than the vehicle, olanzapine and haloperidol groups. GAD-67 mRNA expression in the globus pallidus was decreased following additional treatment with olanzapine or haloperidol, but not clozapine. Changes in expression of other transcripts were not detected. These findings demonstrate important differences in the effects of typical and atypical antipsychotics on chronic vacuous chewing movements.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Dyskinesia, Drug-Induced; Gene Expression; Haloperidol; In Situ Hybridization; Injections, Intramuscular; Male; Mastication; Olanzapine; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Receptors, N-Methyl-D-Aspartate; RNA, Messenger