Olanzapine Shows No Advantage Over Haloperidol for Schizophrenia

Nov. 25, 2003 — Olanzapine therapy did not demonstrate advantages over haloperidol in the treatment of schizophrenia, according to results of a double-blind, randomized, multicenter controlled trial, reported in the Nov. 26 issue of The Journal of the American Medical Association. Olanzapine is the most commonly used atypical antipsychotic medication for the treatment of schizophrenia, with worldwide sales reaching $3.7 billion dollars in 2002, according to the study.

Although previous studies concluded that olanzapine was associated with greater improvement in symptoms and quality while lowering total health costs, recent reviews report that low retention rates have left these conclusions questionable, according to Robert Rosenheck, MD, from the Department of Veterans Affairs (VA) Medical Center in West Haven, Connecticut, and colleagues. The authors hypothesized that in a large, long-term, randomized trial, "olanzapine would outperform haloperidol on three primary outcomes, as demonstrated by fewer symptoms, better quality of life, and lower costs in patients with schizophrenia."

They enrolled 309 patients previously diagnosed with schizophrenia at 17 VA hospitals. The patients had serious symptoms and dysfunction for the previous two years, including inability to work or social constriction. Of those 309 patients, 150 were randomized to receive 5 to 20 mg of haloperidol and 1 to 4 mg prophylactic benztropine mesylate daily, while 159 patients received 5 to 20 mg olanzapine and benztropine placebo. Dose adjustments were made in 5-mg intervals for both groups, up to 20 mg.

Fifty-nine percent of patients completed the study, while 39% partially completed the year-long assessment period. There were no significant differences between the olanzapine group and the haloperidol group in completion rates (45.9% vs. 39.3%; P = .25), nor in reasons for discontinuation.

Intention-to-treat analysis showed comparable scores on the Positive and Negative Syndrome Scale (PANSS) over 12 months, both on total score (P = .35), and positive and negative subscales (P = .64 and P = 0.31, respectively). The haloperidol cohort did achieve higher scores on the Heinrichs-Carpenter Quality of Life Scale (QOLS), but only at six weeks (P = .04), and overall there were no significant differences between the groups (P = .71).

Patients in the olanzapine group had significantly lower scores for akathesia, but not for tardive dyskinesia or other extrapyrimidal symptoms. Weight gain was also more frequently reported in the olanzapine group both at six months (P = .002) and at one year (P = .01). Although no significant differences in costs for VA service use or treatment were found between the two groups, olanzapine medication costs were four to five times higher, resulting in a $3,000 to $9,000 increase in total annual health costs.

The authors point out that the major limitations of the study included lack of follow-up data (although similar in both groups), the preponderance of men in the study (96%), and the dose limitation to 20 mg/day. However, results based on all data do not differ from those at three months, when protocol adherence was high. "Although we did not meet our power target of 600 patients, we still had 80% power to detect a 6% difference between groups on the PANSS and an 11% difference on the QOLS, both notably smaller than generally accepted difference of 20% needed for clinical significance," the authors explain. In both cases, average differences were less than 2%.

"The study found no statistically or clinically significant advantages of olanzapine for schizophrenia on measures of compliance, symptoms, or overall quality of life," the authors write. Cognitive gains in the olanzapine group were insufficient to improve QOLS functioning, and use of this medication was associated with more frequent reports of weight gain and significantly greater total VA costs. "It is clear that olanzapine is not a dominant choice (ie, it does not have both superior outcomes and lower cost)."

The study was supported by Lilly, which provided study drug and placebo, and the VA Cooperative Studies Program. Dr. Rosencheck has received grant support from Lilly, AstraZeneca, and Bristol-Myers Squibb. Dr. Davis has received research grants from Lilly. Dr. Evans has served as a consultant to Janssen and Lilly. Dr. Herz has served as a consultant and speaker and has received research grant support from Lilly.

Uno studio condotto in 17 Centri del Department of Veternas Affairs tra il 1998 ed il 2000 ha valutato l’efficacia dell’Olanzapina (Zyprexa) rispetto all’Aloderidolo ( Haldol , Serenase ) nel trattamento della schizofrenia.

Hanno preso parte allo studio 309 pazienti con diagnosi di schizofrenia o di disturbo schizoaffettivo, e con gravi sintomi e disfunzioni nei precedenti 2 anni.

Il 59% dei pazienti ha completato lo studio , mentre il 36% solo parzialmente.

I pazienti sono stati assegnati in modo random a ricevere Olanzapina ad un dosaggio flessibile ( 5-20mg/die ) con un trattamento profilattico di Benztropina ( 1-4 mg/die ) (n=159), oppure Aloperidolo ( 5-20 mg/die ) (n=150), per 12 mesi.

Non è stata osservata alcuna differenza tra i gruppi per quanto riguardava: sintomi positivi, negativi, o generali della schizofrenia, qualità della vita, sintomi extrapiramidali.

L’Olanzapina era associata ad una minore incidenza di acatisia ( p<0.001 ) e a sintomi più ridotti di discinesia tardiva.
Piccoli ma significativi vantaggi sono stati anche osservati riguardo alla funzione motoria e cognitiva ( memoria ).

I pazienti trattati con Olanzapina hanno presentato più frequentemente aumento di peso.

Secondo gli Autori dello studio il trattamento con Olanzapina non ha mostrato vantaggi rispetto a quello con Aloperidolo.

I benefici dell’Olanzapina nel ridurre l’acatasia e nel migliorare la funzione cognitiva sono bilanciati dall’aumento di peso e dai più alti costi. ( Xagena2003 )

Rosenheck R et al, JAMA 2003; 290:2693-2702

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