BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.
In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.
"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.
In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.
Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.
Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.
After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.
Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.
The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.
EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.
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