Commentaries |
Neuroleptics reconsidered
Address correspondence to Dr A. Daniels. email: anthony.daniels{at}wanadoo.fr
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Introduction |
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 Top Introduction Neuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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This is a response to the Commentary by Dr Charlton (Why are doctors still prescribing neuroleptics?) in this issue of QJM.10 Perhaps it would be best to begin by summarizing his argument.
He states that neuroleptics do not cure schizophrenia, that they create dependency, and that they have many undesirable side-effects, even fatal ones. He states that, insofar as they appear to effect an improvement in the condition for which they are prescribed, it is by means of some of the very effects that are generally deemed undesirable, namely Parkinsonism and over-sedation. In other words, the desired and undesired effects are one and the same. Finally, he states that the undesired effects are so bad that it would be better if patients were treated with safer sedatives, such as benzodiazepines.
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Neuroleptics not a cure for schizophrenia |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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As far as I am aware, no one has ever claimed, or at least not for a long time, that neuroleptics were a cure for schizophrenia, in the sense that antibiotics are a cure for bacterial pneumonia. It is certainly not news that neuroleptics are totally ineffective in some cases, or that they may produce only partial improvement in many others. If medicine were deprived of all treatments that were not cures, there would be little left of the pharmacopoeia.
Dr Charlton also argues that neuroleptics create dependency, in the sense of addiction, because patients with chronic schizophrenia who stop them are liable to further psychosis. This is like saying that insulin creates dependency because the blood sugar of diabetics who stop taking it rises. The bad connotations of one sense of the word ‘dependence’ are being surreptitiously transferred to another sense. Someone who takes thyroxine every day for hypothyroidism is dependent upon it; there is nothing sinister in this.
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Unwanted effects of neuroleptics |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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Again, it is hardly news that neuroleptics have many, very serious side-effects; but to emphasize them to the exclusion of the seriousness of the condition for which they are used is like expressing horror at the side-effects of cytotoxics without mentioning that leukaemia is fatal without them.
Schizophrenia is a chronic and disabling disease, with dire consequences for the person suffering it, his relatives and society as a whole. For example, male schizophrenics were found in one study to have a rate of conviction for assault and serious violence 3.9 times as high as patients with other diagnoses, and female schizophrenics 5.3 times as high.1 Three-quarters of assaults committed by schizophrenics are motivated in their behaviour by their delusions.2 Treated schizophrenics have no higher a rate of violence than other people.3
In the circumstances, I think it is a little cavalier to regard the non-violence of treated schizophrenics compared with untreated ones as mere ‘social docility’, as if their violence served some illegitimately-suppressed purpose. I doubt that Mrs Zito, whose husband was killed by the untreated schizophrenic, Christopher Clunis, would see it that way.
Attempts to control the disturbed and disturbing behaviour of schizophrenics before the advent of neuroleptics now appear bizarre to us. They ranged from the whirling chair to insulin coma therapy. My own particular favourite is the use of croton oil,4 presumably on the theory that a man could not attend to his bowels and his hallucinations at the same time.
It is quite true that neuroleptics can lead to movement disorders and emotional blunting. However, the matter is not quite as straightforward as Dr Charlton appears to think. Movement disorders of many different kinds were described in schizophrenia well before neuroleptics were ever used,5 and emotional blunting was described in schizophrenia both by Kraepelin and Bleuler,6 likewise many years before the use of neuroleptics.
There is disturbing evidence that the use of neuroleptic medications may be associated with the premature death of schizophrenic patients.7 Not only is there a dose–response relationship, but polypharmacy (the use of more than one neuroleptic at a time) is closely associated with premature death. However, high dose and polypharmacy might also be signs of the seriousness of the schizophrenia and the desperation of those treating it. The increased mortality of schizophrenics is, in any case, nothing new: 43% of schizophrenics admitted to hospital in a series published in 1932 died within 5 years of admission.8
As it happens, I have observed in person the results of a natural experiment in the non-treatment of schizophrenics. It is not permissible in British prisons to treat patients against their will, except under the doctrine of necessity, which is to say in a dire emergency; patients who require but refuse treatment must be transferred under a Section of the Mental Health Act to a hospital outside the prison. However, because of a shortage of beds in the NHS, patients are often left in prison untreated for weeks or even months.
Suffice it to say that the consequences have left me with some insight into the reasons why our ancestors tried such apparently absurd or cruel methods as the whirling chair.
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The identity of desired and undesired effects |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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Dr Charlton maintains that the therapeutic effect of neuroleptics is achieved by rendering patients physically immobile in a Parkinsonian way, as well as by creating a state of mental apathy and emotional blunting. He says that the Parkinsonian state, comprising both physical immobility and mental torpor, is the sole mechanism of the efficacy of neuroleptics in schizophrenia, and presumably in other psychotic states in which they are used. However, he provides no evidence that this is so.
There is no doubt that neuroleptics wrongly or overenthusiastically prescribed can result in a zombie-like state. In prisons, chlorpromazine used to be known as ‘the liquid cosh.’ It was frequently prescribed, in huge doses, to those who were merely awkward or aggressive rather than psychotic, and it was indeed the aim of the prescriber to render them so sedated, slow, immobile and apathetic that they could cause no further trouble to the authorities.
But it does not follow from this that sedation, immobility and apathy are the goal of psychiatrists when they prescribe neuroleptics for schizophrenics. Oncologists do not aim at hairlessness in their patients, though they often produce it. Neuroleptics vary in their sedative properties and in their propensity to produce extra-pyramidal symptoms. There is no correlation between antipsychotic efficacy on the one hand and sedative properties on the other, or with the production of extra-pyramidal symptoms.
Trifluoperazine, for example, is very weakly sedative (and may sometimes even have an alerting effect). It has a marked propensity to produce extra-pyramidal side-effects, though many patients experience no such effects while taking it. It is, however, strongly antipsychotic, and not only or even especially in cases in which it produces extra-pyramidal side effects. In other words, its antipsychotic action is completely independent of both its sedative qualities and its propensity to produce Parkinsonism.
Chlorpromazine is strongly sedative, moderately productive of extra-pyramidal symptoms and weakly antipsychotic; risperidone is weakly sedative, weakly productive of extra-pyramidal symptoms and strongly antipsychotic. I trust there is no need further to labour the point. It may be, of course, that psychiatrists do want sometimes to sedate their patients, at least for a time. Where patients are over-excited, sometimes dangerously so, it is only natural and indeed advisable that they should be calmed. But the idea that psychiatrists (whether they know it or not) are aiming to produce, or cannot with due care and attention avoid producing, a tribe of zombies, is preposterous.
The reason that the treatment of schizophrenics with neuroleptics reduces their propensity to violence is not because they are so immobilized physically and volitionally that they are incapable of further violence, but because they no longer suffer, at least so insistently, from the delusions and hallucinations that cause them to commit it in the first place. It is true that many patients find the side-effects of neuroleptics so unpleasant that they refuse to take them. They have other reasons for non-compliance as well, of course; for example, that they do not believe that they were ever ill, or would be ill again if they do not taken their medication. The coercive powers of psychiatry (easily abused) are therefore not necessitated solely or even principally by the unwillingness of patients to take medication that has unpleasant side-effects; psychiatric conditions themselves can and often do deprive them of proper judgement.
Dr Charlton asks whether doctors would choose neuroleptic treatment for themselves or their relatives if they had schizophrenia. I can only answer for myself, that in many circumstances (although not quite in all) I would. If I were happily deluded, and not being a nuisance to others, and if treatment would not effect a complete restoration to my status quo ante, I would not. Otherwise, I would.
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Suggested treatment with benzodiazepines |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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Dr Charlton does not go as far as the anti-psychiatrists of the 1960s and 70s. He does not suggest that psychosis is an exciting voyage into inner space, or that it is a natural and healthy response to an insane world. He appears to accept schizophrenia as a nosological entity. He appears also to think that its manifestations are often in need of treatment. He suggests that benzodiazepines, or sedative anti-histamines, would be the drugs of choice.
But there is no evidence that these drugs are effective in psychoses such as schizophrenia. There is every reason to think that they are not. A review of trials found that, while neuroleptics were efficacious in reducing the symptoms of schizophrenia, barbiturates were not.9 Clinical experience of benzodiazepines used alone in psychosis is not encouraging; huge doses would be needed to produce any effect at all.
Oddly enough, benzodiazepines do have the potential for producing precisely the problems of dependence that Dr Charlton says are characteristic of prolonged use of neuroleptics. The addictive properties of diazepam and lorazepam were, in fact, the subject of the largest class action in British legal history. Abrupt withdrawal from benzodiazepines can result in epileptic fits and can also produce a syndrome indistinguishable from delirium tremens.
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Conclusions |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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It is generally accepted that neuroleptics are not a cure for or complete answer to schizophrenia, and it is also generally accepted that they have many and serious side-effects. It is not true that their therapeutic effect is the consequence only of their sedative properties, or of their ability to immobilize patients both physically and volitionally. There is no reason to think that benzodiazepines have a significant role to play in the treatment of schizophrenia. Doctors have the duty to weigh up the benefits and drawbacks of all treatments; even when this has not always been done well in the past, there is no reason not to do so now. It cannot be done without an appreciation of the natural course of the condition to be treated, and of the alternative treatments.
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References |
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TopIntroductionNeuroleptics not a cure...Unwanted effects of neurolepticsThe identity of desired...Suggested treatment with...ConclusionsReferences |
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1. Wessely SC, Castle D, Douglas AJ, et al. The criminal careers of incident cases of schizophrenia and other psychiatric patients. Psychological Med 1994; 24:483–502.
2. Taylor PJ, Leese M, Williams D. Mental disorder and violence. Br J Psychiatry 1998; 172:218–26.
3. Steadman HJ and Mulvey EP, et al. Violence by people discharged from acute psychiatric inpatient facilities and by others in the same neighbourhoods. Arch Gen Psychiatry 1998; 55:393–401.
4. Lomax M. The Experiences of an Asylum Doctor 1921;London George Allen and Unwin.
5. Lagriffe L. Les troubles du movement dans la demence precoce 1913;Paris Masson et Cie.
6. Kraepelin E. Lectures on Clinical Psychiatry 1913; 8th edn. London, Balliere Tindall & Cox.
7. Joukamaa M and Heliovaara M, et al. Schizophrenia, neuroleptic medication and mortality. Br J Psychiatry 2006; 188:122–7.
8. Wing JK. Course and Prognosis of Schizophrenia. In Wing JK and Wing L (Eds.). Handbook of Psychiatry 1982;Cambridge University Press Vol. 3:.
9. Davis JM and Garver DL. Neuroleptics: clinical use in psychiatry. In Iversen LL and Iversen SD (Eds.). Handbook of Psychopharmacology|. 1978;New York Plenum Press Vol. 10: Neuroleptics and Schizophrenia.
10. Charlton BG. Why are doctors still prescribing neuroleptics? Q J Med 2006; 99:417–20.
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