Anticholinergic use in hospitalised schizophrenic patients in Belgium.
De Hert M, Wampers M, van Winkel R, Peuskens J;
Commented by , 30 Apr 2007
Aim of the study
The debate about the superiority of the second generation antipsychotics (SGA) goes on. The clearest advantage of these compounds is a lower risk of extrapyramidal side-effects (EPS) compared to high-potency first generation antipsychotics (FGA) such as haloperidol.
Nevertheless, only a few studies have compared SGA with low-potency first generation compounds and there is also only a limited number of reports in naturalistic settings. In this context the authors conducted a study in psychiatric hospitals in Belgium to compare the EPS risk of various antipsychotics under naturalistic conditions.
Method
The drug use of 1215 patients with a diagnosis of schizophrenia or related disorders (DSM-IV 295.xx) was recorded. Antipsychotic drug use was classified into four categories:
- treatment only with first generation antipsychotics, i.e. patients receiving one or several FGA
- combined treatment of a high potency FGA and a SGA
- combined treatment of a low potency FGA and a SGA, and
- monotherapy with a SGA: patients receive one or a combination of SGA.
EPS were measured with rating scales and analysing the use of anticholinergic medication as a proxy for EPS.
Results
The lower EPS risk of FGA found in double-blind registrational studies was confirmed by highest use of anticholinergic medication in patients treated with high potency FGA (alone or combined with SGA). Less anticholinergic medication was used in participants who only received SGA and who received a combination of SGA and low potency FGA.
There was, however, no difference between the latter two groups. Furthermore, there were no significant differences between groups in the frequency of specific EPS with the exception of akathisia which occurred more frequently under FGA compared to SGA. Thus, the use of antiparkinson medication reduced EPS under treatment with FGA to an important degree.
Dr Leucht's comments
It is now very clear that SGA induce fewer EPS than haloperidol. Even when the latter was used in very low doses (approximately 2 mg on the average) it induced more EPS than risperidone in a study on first episode patients with schizophrenia (ref. 1).
This finding is important, because haloperidol was the standard antipsychotic in most industrialized countries. Nevertheless, a more recent debate focuses on the question as to whether the EPS can also be avoided by using low-potency conventional antipsychotics or by using prophylactic antiparkinson medication.
Leucht et al. (ref. 2) found that the EPS superiority of SGA compared to low-potency FGA was dose related, and that there may be no difference as long as chlorpromazine is used in doses below 600 mg/day. Similarly to the current study Rosenheck et al. (ref. 3) found that with the exception of akathisia and tardive dyskinesia haloperidol combined with prophylactic antiparkinson medication did not induce more EPS than olanzapine.
Guidelines were hesitant about the recommendation to use prophylactic antiparkinson medication, but these recent studies support its use when high potency FGA are administered. The current evidence base is, however, too small to allow for a judgement whether the addition of antiparkinson medication is sufficient to turn FGAs into SGAs.
References
1. Schooler N, Rabinowitz J, Davidson M, Emsley R, Harvey PD, Kopala L, et al. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. American Journal of Psychiatry 2005; 162 (5); 947-953. Free full text article
2. Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 2003; 361 (9369); 1581-1589
3. Rosenheck R, Perlick D, Bingham S, Liu-Mares W, Collins J, Warren S, et al. Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. JAMA 2003; 290 (20); 2693-2702