THE DEFINITIVE 2005 STUDY OF ATYPICAL ANTI-PSYCHOTICS BY JEFFREY LIEBERMAN ET AL

                                                                 

JEFFREY LIEBERMAN'S GOBSMACKING PAPER IN THE NEW ENGLAND JOURNAL OF MEDICINE (2oo5)

METHODS

A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.

Full Text of Methods...

RESULTS

Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.

                                 JEFFREY LIEBERMAN, COLUMBIA UNIVERSITY

                                                                             

                                                                 Susan Shortreed

                                                                           

                                                                             

                                                                 Erica Moodie

             ESTIMATING THE OPTIMAL DYNAMIC TREATMENT REGIME (Shortreed and Moodie, 2012)

Treatment of schizophrenia is notoriously difficult and typically requires personalized adaption of treatment due to lack of efficacy of treatment, poor adherence, or intolerable side effects. The Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) Schizophrenia Study is a sequential multiple assignment randomized trial comparing the typical antipsychotic medication, perphenazine, to several newer atypical antipsychotics. This paper describes the marginal structural modeling method for estimating optimal dynamic treatment regimes and applies the approach to the CATIE Schizophrenia Study. Missing data and valid estimation of confidence intervals are also addressed.

 Susan Shortreed is effectively suggesting that patients should successively switch their atypical anti-psychotics and hence experience a variety of potentially debilitating side effects. However all of these toxic psych meds poison the enzymes and they are all as potentially bad as the other. I have tried corresponding on these issues with Dr. Shortreed, but she did not respond, even though her paper was published in the Journal of the Royal Statistical Society, and I expressed my concerns as a Fellow of this Society.

Deirdre Oliver Dr. Lieberman reports having received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer, and Solvay. Dr. Stroup reports having received research funding from Eli Lilly and consulting fees from Janssen Pharmaceutica, GlaxoSmithKline, and Bristol-Myers Squibb. Dr. McEvoy reports having received research funding from AstraZeneca, Forest Research Institute, Eli Lilly, Janssen Pharmaceutica, and Pfizer; consulting or advisory-board fees from Pfizer and Bristol-Myers Squibb; and lecture fees from Janssen Pharmaceutica and Bristol-Myers Squibb. Dr. Swartz reports having received research funding from Eli Lilly and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, and Pfizer. Dr. Rosenheck reports having received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, and Eli Lilly and consulting fees from Bristol-Myers Squibb, Eli Lilly, and Janssen Pharmaceutica. Dr. Perkins reports having received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Otsuka Pharmaceutical, Eli Lilly, Janssen Pharmaceutica, and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, and Pfizer. Dr. Keefe reports having received research funding from AstraZeneca, Eli Lilly, and Janssen Pharmaceutica; consulting or advisory-board fees from Forest Pharmaceuticals, Eli Lilly, Janssen Pharmaceutica, Pfizer, and Bristol-Myers Squibb; and lecture fees from Eli Lilly and Janssen Pharmaceutica. Dr. Sonia Davis is an employee of Quintiles. Dr. Clarence Davis reports having received consulting fees from Eli Lilly and Quintiles. Dr. Lebowitz is a former employee and Ms. Severe and Dr. Hsiao are current employees of the NIMH.

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Deirdre Oliver The face of a cold blooded opportunist.