Methodological problems in clinical trials comparing anticholinergic drugs in the treatment of neuroleptic-induced EPS may have contributed to this debate. In many studies distinction between different types of EPS has not been made, and in some efficacy has been classified on a present/absent criteria. Moreover, most trials are not placebo controlled (Bezchlibnyk-Butler & Remington, 1994). Identification of EPS has been based on subjective reporting by the patient and objective observation by the experimenter. However, even if the presence of a measurable change on physical examination for the signs and symptoms of EPS is observed and/or is reported by subjects, the level of distress and disability necessitating treatment cannot be measured easily. Individual tolerance for EPS varies markedly and so do the prevalence rates of EPS in different surveys (Johnson, 1978; Caradoc-Davies et al, 1986). Initial prophylaxis and acute treatment of EPS.
Development of EPS is a clear indication for requirement of an anticholinergic drug. Benzchlibuyk-Butler & Remington (1994) reviewed studies and case reports on efficacy of anticholinergic drugs in the treatment of neuroleptic-induced EPS and broadly categorised efficacy of these agents on specific EPS (see Table IV).
|
Anticholinergic drugs | Tremor | Rigidity | Dystonia | Akinesia | Akathisia |
| Benzhexol | + + | + + | + + | + + + | + + |
| Benztropine | + + | + + + | + + + | + + | + + |
| Biperiden | + + | + + | + + | + + + | + + |
| Orphenadrine | + + | + + | -- | + + | + + |
| Procyclidine | + + | + + | + + | + + | + + |
| + + + = >50% response | + + = 20-25% response | -- = no effect |
Amongst the EPS, anticholinergic drugs have been suggested a treatment of choice for acute dystonia. Although earlier studies (e.g. DiMascio & Demirgian, 1970; Swett et al, 1977) suggested that anticholinergic prophylaxis for neuroleptic-induced acute dystonia might be unnecessary, others (Stern & Anderson, 1979; Keepers et al, 1983; McEvoy, 1983; Lake et al, 1986; Sramek et al, 1986; Winslow et al, 1986; Manos et al, 1986; Boyer et al, 1987; Arana et al, 1987) have concluded that concurrent use of anticholinergic drugs may reduce the rate of neuroleptic-induced dystonia.
Levin & Rifkin (1991a) reviewed retrospective as well as prospective studies of initial prophylaxis with anticholinergic drugs for prevention of EPS and concluded that there was evidence to support the use of initial prophylaxis for the prevention of acute dystonic reactions, however, they were unable to find any definitive study on the prevention of other types of EPS by initial prophylaxis. Arana et al (1988) from their analysis of studies comparing the incidence of acute dystonia induced by neuroleptic agents concluded that the benefit of anticholinergic prophylaxis of neuroleptic-induced acute dystonia was greater with high-potency neuroleptics than with low-potency neuroleptics.
The WHO consensus statement (1990) on the prophylactic use of anticholinergics in patients on long-term neuroleptic treatment recommended that
"as a rule these compounds should be used only when parkinsonism has actually developed, and when other measures, such as the reduction of neuroleptic dosages or the substitution of the administered drug by another less prone to induce parkinsonism have proven ineffective". In the past, others (Klett et al, 1972; McClelland et al, 1974; Pullen et al, 1984) have also come to the conclusion that anticholinergic drugs should be withdrawn after three months as drug-induced parkinsonism tends to improve over this time despite continued antipsychotic medication. Following the same line of management, Pullen et al (1984) suggested that it is possible to limit the administered anticholinergic drugs for 7-10 days after depot antipsychotic injection.