Prophylactic treatment with atypical neuroleptic drugs of people who have not manifested a psychological crisis carries an enormous burden of ethical responsibility. This is because of the severe risks of drug-induced diseases incurred by taking neuroleptics. There is an extraordinary range of these drug-induced diseases, and sometimes the manufacturers' warnings in advertisements published in psychiatric journals run to two pages of extremely small type.
The more serious adverse reactions, such as agranulocytosis[40] and neuroleptic malignant syndrome,[41] may cause sudden death. The manufacturers also warn that laboratory evidence indicates the new drugs are carcinogens[42] and mutagens.[43] Despite the claims from some quarters that tardive dyskinesia is not a problem with atypicals, most of the drug companies warn that their drugs do cause the disease. An advertisement for Risperdal (risperidone) clearly warns about this risk.[44]
The manufacturers also warn about the possibility of adverse mental and behavioural reactions. Many of these psychiatric reactions are the very disorders that treatment with the drugs is intended to prevent. An advertisement published by Zeneca Pharmaceuticals, for instance, after warning about an extraordinary variety of ways their new atypical quetiapine (Seroquel) can induce ill-health, identifies ‘Other Adverse Events Observed During the Pre-Marketing Evaluation of Seroquel’. These include: "abnormal dreams, dyskinesia, thinking abnormal, tardive dyskinesia, vertigo, involuntary movements, confusion, amnesia, psychosis, hallucinations, hyperkinesia, libido increased, urinary retention, incoordination, paranoid reaction, abnormal gait, myoclonus, delusions, manic reaction, apathy, ataxia, depersonalisation, stupor, bruxism, catatonic reaction, hemiplegia."[45]
A Clozaril (clozapine) advertisement also warns about the risk of a variety of drug-induced negative and positive symptoms such as loss of speech, amentia, delusions/hallucinations and paranoia.[46] If treatment with atypical neuroleptics can sometimes induce psychosis, hallucinations and delusions, as is frankly admitted by the manufacturers, questions most definitely arise about the application of these drugs as prophylactics against psychosis. In the long term, will prophylactic treatment actually increase the incidence of psychosis? This question does not seem to have been considered in the psychiatric literature.
Another question to be addressed concerns how to interpret the significance of transition to psychosis by a person who has been receiving prophylactic drug treatment. Given the nature of traditional thinking in the field, such an event will probably be taken to indicate accuracy in the diagnosis of prodromal symptoms but ineffectiveness in the prophylactic treatment. This interpretation might encourage the prescription of increased doses of prophylactic drug treatment for other patients. But if it is clear that psychosis can be induced by the drugs themselves, as the manufacturers warn, such an event could simply indicate an adverse drug reaction. This interpretation would be a warning that other patients should be taken off their prophylactic medication altogether, rather than have their dosage increased. Once again, these lines of discussion do not arise in the literature.
Perhaps the most insidious of the ethical burdens for the promoters of the prophylactic use of atypicals comes from the growing body of evidence that withdrawal from some of these drugs can sometimes cause a psychotic reaction. Withdrawal reactions from typical neuroleptics have long been documented. It is now becoming apparent that the brain chemistry of some people treated with atypicals is changed in a way that makes them dependent on continued treatment. When atypical neuroleptic treatment is withdrawn from them they experience an immediate psychotic reaction that can only be rectified by recommencement of treatment.[47]
The ethical burden for psychiatrists treating the supposed prodrome of schizophrenia will include resisting the temptation to interpret psychosis induced by atypical withdrawal as merely being evidence that the person was correctly diagnosed in the first place. Psychiatrists will be tempted to argue that it was the prophylactic treatment which, up to the point of withdrawal, prevented the person from entering psychosis. In this way the original diagnosis and prophylactic treatment could easily be vindicated, when in fact they might both be at fault.
Next: Is Preventive Medicine for Schizophrenia Valid?
[40] Novartis (Sandoz Pharmaceuticals Corporation), Clozaril (clozapine) advertisement, Archives of General Psychiatry, Vol. 55, No. 1, January 1998, p. 8.
[41] Janssen Pharmaceutica, Risperdal (risperidone) advertisement, Psychiatric Services, Vol. 49, No. 9, September 1998, p. 1124.
[42] Eli Lilly and Company, Zyprexa (olanzapine) advertisement, Psychiatric Services, Vol 49, No. 3, March 1998, p. 310.
[43] Zeneca Pharmaceuticals, Seroquel (quetiapine) advertisement, Psychiatric Services, Vol. 49, No. 3, March 1998, p. 284.
[44] Risperdal (risperidone) advertisement, op.cit.
[45] Seroquel (quetiapine) advertisement, op.cit.
[46] Clozaril (clozapine) advertisement, op.cit.
[47] J. K. Stanilla, J. de-Leon and G. M. Simpson, ‘Clozapine withdrawal resulting in delirium with psychosis: a report of three cases’, pp. 252–5.