Why are doctors still prescribing neuroleptics?
Reader in Evolutionary Psychiatry
School of Biology and Psychology
University of Newcastle upon Tyne
There are two main pharmacological methods of suppressing undesired behavior: by sedation or with neuroleptics. Traditionally, the invention of neuroleptics has been hailed as one of the major clinical breakthroughs of the twentieth century, since they calmed agitation without (necessarily) causing sedation. The specifically neuroleptic form of behavioral control is achieved by making patients psychologically Parkinsonian – which entails emotional-blunting and consequent demotivation. Furthermore, chronic neuroleptic usage creates dependence so that - in the long term, for most patients - neuroleptics are doing more harm than good. The introduction of ‘atypical’ neuroleptics (ie. neuroleptically-weak but strongly sedative neuroleptics) has made only a difference in degree, and at the cost of a wide range of potentially fatal metabolic and other side effects. It now seems distinctly possible that, for half a century, the creation of many millions of Parkinsonian patients has been misinterpreted as a ‘cure’ for schizophrenia. Such a wholesale re-interpretation of neuroleptic therapy represents an unprecedented disaster for the self-image and public reputation of both psychiatry and the whole medical profession. Nonetheless, except as a last resort, neuroleptics should swiftly be replaced by gentler and safer sedatives.
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It is usually said, and I have said it myself, that the invention of neuroleptics was one of the major therapeutic breakthroughs of the twentieth century . But I now believe that this opinion is due for revision, indeed reversal. Neuroleptics have achieved their powerful therapeutic effects at too great a cost, and a cost which is intrinsic to their effect [2, 3]. The cost has been many millions of formerly-psychotic patients who are socially-docile but emotionally-blunted, de-motivated, chronically neuroleptic-dependent and suffering significantly increased mortality rates. Consequently, as a matter of some urgency, neuroleptic prescriptions should be curtailed to the point that they are used only as a last resort.
Behavioral suppression in medicinePsychiatrists, especially those working in hospitals, have frequent need for interventions to calm and control behavior – either for the safety of the patient or of society. The same applies – less frequently – for other medical personnel dealing with agitation, for example due to delirium or dementia. Broadly speaking, there are two pharmacological methods of suppressing agitated behavior: with sedatives or with neuroleptics [2, 3].
Sedation was the standard method of calming and controlling psychiatric patients for many decades prior to the discovery of neuroleptics, and sedation remained the only method in situations where neuroleptics were not available (eg in the Eastern Bloc and under-developed countries) [3, 4].
The therapeutic benefits of sedation should not be underestimated. In the first place sedation can usually be achieved safely and without sinister side effects; and an improved quality of sleep makes patients feel and function better. Sedation may also be potentially ‘curative’ where sleep disturbance has been so severe and prolonged as to lead to delirium, which (arguably) may be the case for some psychotic patients such as those with mania [2, 5].
But clearly - except in the short term - sedation is far from an ideal method of suppressing agitation. The discovery of neuroleptics offered something qualitatively new in terms of behavioral control: the possibility of powerfully calming a patient without (necessarily) making them sleepy . In practice, sedative neuroleptics (such as chlorpromazine or thioridazine), or a combination of a sedative (such as lorazepam or promethazine) with a less-sedating neuroleptic such as haloperidol or droperidol, were often used to combine both forms of behavioral suppression.
The Parkinsonian core effect of neurolepticsThe Parkinsonian (emotion-blunting and de-motivating) core effect of neuroleptics has been missed by most observers. This failure relates to a blind-spot concerning the nature of Parkinsonism.
Parkinsonism is not just a motor disorder. Although abnormal movements (and an inability to move) are its most obvious feature, Parkinsonism is also a profoundly ‘psychiatric’ illness in the sense that emotional-blunting and consequent de-motivation are major subjective aspects. All this is exquisitely described in Oliver Sack’s famous book Awakenings , as well as being clinically apparent to the empathic observer.
Emotional-blunting is de-motivating because drive comes from the ability subjectively to experience in the here-and-now the anticipated pleasure deriving from cognitively-modeled future accomplishments . An emotionally-blunted individual therefore lacks current emotional rewards for planned future activity, including future social interactions, hence ‘cannot be bothered’.
Demotivation is therefore simply the undesired other side of the coin from the desired therapeutic effect of neuroleptics. Neuroleptic ‘tranquillization’ is precisely this state of indifference . The ‘therapeutic’ effect of neuroleptics derives from indifference towards negative stimuli, such as fear-inducing mental contents (such as delusions or hallucinations); while anhedonia and lack of drive are predictable consequences of exactly this same state of indifference in relation to the positive things of life.
So, Parkinsonism is not a ‘side-effect’ of neuroleptics, neither is it avoidable. Instead, Parkinsonism is the core therapeutic effect of neuroleptics: as reflected in the name, which refers to an agent which ‘seizes’ the nervous system and holds it constant (ie. indifferent, blunted) . Demotivation should be regarded as inextricable from the neuroleptic form of tranquillization . And the so-called ‘negative symptoms’ of schizophrenia are (in most instances) simply an inevitable consequence of neuroleptic treatment .
By this account, the so-called ‘atypical’ neuroleptics (risperidone, olanzapine, quetiapine etc.) are merely weaker Parkinsonism-inducing agents. The behavior-controlling effect of ‘atypicals’ derives from inducing a somewhat milder form of Parkinsonism, combined with strong sedation . However, clozapine is an exception, because clozapine is not a neuroleptic, does not induce Parkinsonism, and therefore (presumably) gets its behavior- controlling therapeutic effect from sedation. The supposed benefit from clozapine of ‘treating’ the ‘negative symptoms of schizophrenia’ (such as de-motivation, lack of drive, asocial behavior etc.) is therefore that – not being a neuroleptic – clozapine does not itself cause these negative symptoms.
What next?Whatever the historical explanation for the wholesale misinterpretation of neuroleptic actions, recent high profile papers in the New England Journal of Medicine [12, 13] and JAMA  have highlighted serious problems with neuroleptics as a class (whether traditional or atypical), and the tide of opinion now seems to turning against them.
In particular the so-called ‘atypical neuroleptics’ which now take up 90 percent of the US market , and are increasingly being prescribed to children  seem to offer few advantages over the traditional agents  while being highly toxic and associated with significantly-increased mortality from metabolic and a variety of other causes [13, 14, 15, 16]. This new data has added weight to the idea that usage of neuroleptics should now be severely restricted [3, 7, 17].
Indeed, it looks as if after some 50 years widespread prescribing there is going to be a massive re-evaluation and re-interpretation of these drugs, with a reversal of their evaluation as a great therapeutic breakthrough. It now seems distinctly possible that for half a century the creation of millions of asocial, neuroleptic-dependent but docile Parkinsonian patients has been misinterpreted as a ‘cure’ for schizophrenia. This wholesale re-interpretation represents an unprecedented disaster for the self-image and public reputation – not just of psychiatry – but of the whole medical profession.
Perhaps the main useful lesson from the emergence of the 'atypical' neuroleptics is that psychiatrists did not need to make all of their agitated and psychotic patients Parkinsonian in order to suppress their behavior. ‘Atypicals’ are weakly neuroleptic but highly sedative. This implies that sedation is probably sufficient for behavioral control in most instances [3, 17]. In the immediate term, it therefore seems plausible that already-existing, cheap, sedative drugs (such as benzodiazepines or antihistamines) offer realistic hope of being safer, equally effective and subjectively less-unpleasant substitutes for neuroleptics in many (if not all) patients.
I would argue that this should happen sooner rather than later. If we apply the test of choosing what treatment we would prefer for ourselves or our relatives with acute agitation or psychosis, knowing what we now know about neuroleptics, I think that many people (perhaps especially psychiatric professionals) would now wish to avoid neuroleptics except as a last resort. Few would be happy to wait a decade or so for the accumulations of a mass of randomized trial data (which may never emerge, since such trials would lack a commercial incentive) before making the choice of less dangerous and unpleasant drugs .
But there is no hiding the fact that if neuroleptics were indeed to be replaced by sedatives then this would seem like stepping-back half a century. It would entail an acknowledgement that psychiatry has been living in a chronic delusional state – and this may suggest that the same could apply to other branches of medicine. Since such a wholesale cognitive and organizational reappraisal is unlikely, perhaps the most realistic way that the desired change in practice will be accomplished is not by an explicit ‘return’ to old drugs but by the introduction of a novel (and patentable) class of sedatives which are marketed as having some kind of (more-or-less plausible) new therapeutic role.
Such a new class of tacit sedatives would enable the medical profession to continue its narrative of building-upon past progress, and retain its self-respect; albeit at the price of cognitive evasiveness. But, if such developments led to a major cut-back in neuroleptic prescriptions, then this deficiency of intellectual honesty would be a small price to pay.
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