Clozapine versus typical antipsychotics a retro- and prospective study of extrapyramidal side effects

Abstract

Schizophrenic patients in long-term neuroleptic monotherapy with clozapine (n = 100) and perphenazine, flupenthixol or zuclopentixol (controls, n = 100) were evaluated for extrapyramidal side effects (EPS) (blind) as well as other side effects and mental condition (non-blind). In both groups the patients had received neuroleptic treatment for a total of 14 years (median) and the present antipsychotic (clozapine or control drug) for 5 years. Thus the clozapine-treated patients had previously received traditional neuroleptics for 9 years (median). The study was both retrospective (0.3-19 years for clozapine, 0.3-24 years for control drug, by means of chart information) and prospective (1 year, with video-controlled evaluation of EPS). There was a significantly lower prevalence of tardive dyskinesia (TD) in clozapine treated patients than control patients, although prior to this treatment there were more TD patients in the clozapine group (P < 0.05). This lower level of TD in the clozapine group was related to a lower induction of new cases (P < 0.001) and a tendency towards greater disappearance of TD in the clozapine than in the control group (P = 0.07). Clozapine treated patients without TD had started clozapine and ceased traditional neuroleptics at an earlier age than those with TD. Parkinsonian signs were seen in 33% of the clozapine patients versus 61% of the control patients, mainly as hypokinesia; tremor in 3% versus 11% and rigidity in 0 versus 19%. Psychic akathisia was found in 14% versus 40% and motor akathisia in 7% versus 29% of the patients, all differences significantly in favor of clozapine. Clozapine treated patients also had less neuroleptic-induced emotional indifference and depression, but more autonomic side effects than controls.

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period

“…In a study similar to ours, it has also been reported that clozapine had very positive clinical effects during five-year period 22 . our results, concerning the safety profile of clozapine, are in agreement with other studies within ambulatory, long-term setting 23 . Neither the cases of significant blood disorders nor the cases of muscle damage were detected in our patients.…”

A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia

“…[57][58][59]64 24% of the patients treated with clozapine and 45% of the patients treated with fi rst-generation antipsychotics present with one or more sexual side effects, including erectile and ejaculatory dysfunction. 65 Studies have shown different results: Knegtering et al 57 found olanzapine-induced sexual dysfunction in 27% of their schizophrenic patients; Montejo et al 59 found it in 10-33%; and Bobes et al found Randomized, double-blind, placebo-controlled crossover study 25 Not effective in improving any domain of sexual functioning despite a signifi cant decrease in prolactin levels …”

Atypical antipsychotics: are some more atypical than others?

“…It should be pointed out, though, that in all of these studies the prevalence and incidence of EPS with clozapine, while low, was not zero. This has also been confirmed in a careful retro-and prospective study of EPS in patients on clozapine versus typical neuroleptics (Gerlach et al 1996). Whether this low incidence represents the lingering effect of previous treatment or is significantly above placebo rates is not clear.…”