There is no clear answer and the debate about the long term use of anticholinergic drugs remains unresolved. This may be due to the fact that EPS do not appear in a consistent manner. Their appearance has not always been found to be consistent with dose, potency and length of administration of neuroleptic, nor with individual (e.g. age, sex, etc.) variables (Swett et al, 1977). Studies of anticholinergic withdrawal have also found that the proportion of patients receiving antipsychotic medication who experience relapse of parkinsonism varies widely from 4% in some studies (e.g. McClelland et al, 1974) to 68% (Manos et al, 1981).
Studies on anticholinergic withdrawal
Several workers have tested the need for maintenance treatment of anticholinergic drugs by utilizing a drug withdrawal paradigm. A recurrence of EPS on withdrawal of anticholinergic drugs would warrant a continuation of anticholinergic treatment for prevention of neuroleptic-induced EPS. Some studies on withdrawal of anticholinergic drugs (e.g. Caroli et al, 1975; Rifkin et al, 1978; Manos et al, 1981) have found that sudden withdrawal of anticholinergic drugs resulted in severe EPS. Manos et al (1981) found that even gradual withdrawal of anticholinergic drugs produced the same frequency and intensity of EPS and found that whether the anticholinergic drug was withdrawn abruptly or gradually, there was severe worsening of EPS in 71% and 68% of patients respectively. However, other studies on patients with chronic schizophrenia on long term neuroleptic medication suggest that when anticholinergic medication is withdrawn, only a small minority of these patients present with EPS of any clinical relevance (e.g. McClelland, 1976) suggesting that it may be safe to discontinue anticholinergic medication in chronic schizophrenia.
Several authors have suggested that anticholinergic medication should be withdrawn after a period of three months (Orlov et al, 1971; Klett et al, 1972). The WHO consensus statement on prophylactic use of anticholinergic drugs in patients on long-term neuroleptic treatment (1990) also recommends its discontinuation in patients whose EPS are under reasonable control. It recommended that anticholinergic drugs may be justified only early in the treatment and should be discontinued after remission of symptoms and its need should be re-evaluated. It further recommends While Lavin & Rifkin (1991b), on the other hand, concluded from their review of double-blind anticholinergic withdrawal studies that a large number of patients without antiparkinsonian treatment will suffer EPS. However, it was not possible to predict which patients were destined to develop EPS on withdrawal of antiparkinsonian drugs. They suggested that prophylactic antiparkinsonian agents are beneficial for most patients on a maintenance basis. Jellinek et al (1981) found that discontinuing anticholinergic drugs may also result in a significant increase in anxiety, depression, motor agitation and hallucinations, physical complaints and total psychopathology score on the Short Clinical Rating Scale (French & Heninger, 1970) in some patients at least. They suggested that these non-motor symptoms would warrant continuation of anticholinergic drugs in this subgroup of patients.
Is it possible to predict who needs treatment with anticholinergic drugs? Anticholinergic drugs are often prescribed routinely and also prophylactically. The research evidence proporting and refuting such practice remains inconclusive and the recommendation that anticholinergic drugs should be administered prophylactically has attracted several critics (Klett et al, 1972; Mindham et al, 1972; McClelland et al, 1974; Mindham 1976; McClelland 1976). Not all patients seem to require treatment with anticholinergic drugs for the prevention of neuroleptic-induced EPS and it is often difficult to predict neuroleptic-induced EPS in a patient taking a particular neuroleptic. Some patients do not develop any EPS on a high dose of high potency neuroleptic, while others develop severe EPS with a small dose of low potency neuroleptic. Therefore, if anticholinergic drugs are used prophylactically many patients are unnecessarily treated with these. Since such treatment results in an increase in morbidity (May & Simpson, 1980), it is important to try and distinguish the group of patients who need prophylactic anticholinergic drugs from those who do not.
Researchers have often found it difficult to predict neuroleptic-induced EPS which has contributed to the controversy surrounding the need for anticholinergic drugs for the purposes of prophylaxis (Keepers and Casey, 1991). Several workers have studied the predictability of EPS on the basis of previous history of anticholinergic use, age, sex, and neuroleptic dose, and demonstrated a relationship between these variables and susceptibility to develop EPS (Swett,1975; Keepers et al, 1983; Keepers & Casey, 1987). Individual susceptibility to EPS has also been demonstrated in non-human primates (Case et al, 1980). Crowley et al (1978) have demonstrated that there is an individual variation in neurotransmitter levels in the brain and in drug metabolism. Moreover, microanatomical variations in specific brain regions (e.g. basal ganglia) may be responsible for variable individual susceptibility to EPS. Casey (1987) has suggested from primate experiments that neuroleptic exposure produces reverse tolerance to EPS. Several variables can influence production of EPS. The dose of neuroleptic may be one such factor which in turn may be influenced by other factors. Johnson (1973, 1975) found that some patients develop new symptoms on a lower dose of neuroleptics (than previously tolerated), while others develop tolerance only to higher doses. Muscular rigidity, tissue damage and injection technique have also been suggested as possible variables in the production of intermittent side effects. Accumulation of neuroleptics in body tissues may be another importnat determinant for production of EPS (Johnson, 1978).
It is important to study possible risk factors to determine the need for anticholinergic medication for management of neuroleptic-induced EPS.