Olanzapine perphenazine

ANTIPSYCHOTICS-CHLORPROMAZINE, CLOZAPINE, HALOPERI-DOL, OLANZAPINE, PERPHENAZINE, RISPERIDONE, SERTINDOLE, THIORIDAZINE, ZUCLOPENTHIXOL H2 RECEPTOR BLOCKERS -CIMETIDINE t plasma concentrations of these antipsychotics, with risk of associated adverse effects Cimetidine is an inhibitor of CYP3A4 (sertindole, haloperidol, risperidone), CYP2D6 (chlorpromazine, risperidone, zudopenthixol, thioridazine, perphenazine) and CYP1A2 (clozapine, olanzapine, sertindole, haloperidol) Avoid concomitant use. Choose an alternative acid suppression, e.g. H2 antagonist... 

Area of assessment Clinically sedative antipsychotics, Less sedative antipsychotics, e.g. chlorpromazine, clozapine, e.g. haloperidol, perphenazine, olanzapine pimozide, sulpiride ... 

Recently, a large study in the USA (CATIE) reported that perphenazine was as effective as atypical antipsychotic drugs, with the modest exception of olanzapine, and concluded that typical antipsychotic drugs are the treatment of choice for schizophrenia based on their lower cost. However, this study did not adequately consider the risk of tardivedyskinesia or the treatment history of patients in the design of this study. 

Moban) olanzapine (Zyprexa) perphenazine (Trilafon) pimozide (Orap) quetiapine (Seroquel) risperidone (Risperdal) thioridazine (Mellaril) thiothixene (Navane) trifluoperazine (Stelazine) trifuluopromazine (Vesprin) ziprasidone (Geodon). 

In 2005, an NIMH multisite study called CATIE compared the older neuroleptic perphenazine (Trilafon) and atypical neuroleptics olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and zipra-sidone (Geodon Lieberman et al., 2005a see also Nasrallah, 2007 Rosenheck et al., 2006 Weiden, 2007a). Phase I involved 1,460 patients diagnosed with schizophrenia initially randomly assigned in a doubleblind study to one of the five neuroleptics. The study lasted 18 months, with safety and tolerability outcomes evaluated at 1, 3, 6, 9, 12, 15, and 18 months. 

Note that perphenazine (Trilafon) is in the middle of the pack there was no statistical difference between it and the leader, olanzapine (Zy-prexa). But Zyprexa had the worst adverse effect profile (see subsequent sections). 

Representative Chemicals Chlorpromazine Tri-flupromazine Promazine Promethazine Ace-promazine Ethopropazine Thioridazine Mesoridazine Piperacetazine Fluphenazine Perphenazine Prochlorperazine Trifluoperazine Acetophenazine Molindone Pimozide Haloper-idol Droperidol Thiothixene Chlorprothixene Clozapine Olanzapine Risperidone Quetiapine Loxapine... 

Carbamazepinewasfound to decrease the plasma levels of phenothiazines by as much as 50% (described with chlorpromazine, perphenazine, and fluphenazine). It has been reported to decrease the serum levels of clozapine by about60-85% due to its hepatic cytochrome P450 (CYP) enzyme-inducing properties. Loxapine may induce carbamazepine metabolism. Carbamazepine has been shown to reduce the plasma levels of risperidone by as much as 50%, while it increases olanzapine clearance by 44% and reduces its half-life by 20%. Carbamazepine increases aripiprazole metabolism through CYP3A4 induction. Thus, the aripiprazoie dose should be doubled. 

ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL, PERPHENAZINE, RISPERIDONE, SERTINDOLE SSRIs Possible t plasma concentrations of these antipsychotics Inhibition of CYP2D6-mediated metabolism of these drugs. The clinical significance of this depends upon whether alternative pathways of metabolism of these substrates are also inhibited by co-adminis-tered drugs. The risk is theoretically greater with clozapine, haloperidol and olanzapine because their CYPl A2-mediated metabolism Is also Inhibited by SSRIs Warn patients to report T side-effects of these drugs, and consider reducing the dose of the antipsychotic... 

Changes in the 10-year risk of coronary heart disease have been compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) in schizophrenia [22 ]. The mean change in 10-year coronary heart disease risk differed significantly between treatments. Olanzapine was associated with a 0.5% increase and quetiapine with a 0.3% increase, while the risk fell in patients who used perphenazine (-0.5%), risperidone (—0.6%), and ziprasidone (—0.6%). The difference in 10-year coronary heart disease risk between olanzapine and risperidone was statistically significant. 

Metabolism A prospective, naturalistic study of 809 patients that compared 10 antipsychotics found there were no significant relationships between any of the antipsychotic drugs and increased waist circumference, HOMA-IR or LDL-cholesterol levels [54 ]. Hypertriglyceridemia was associated with clozapine, reduced HDL-cholesterol with both clozapine and olanzapine, hypertension with perphenazine, and hyperglycaemia inversely with ziprasidone and positively with haloperidol. 

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