A scientific revolution transformed medical care in the second half of the twentieth century. Developments in molecular biology, genetics and other fields resulted in new insights into many diseases, and from this, more effective treatments. More recently this revolution, which began in the laboratory, has transferred to the clinic, as evidence-based medicine (EBM) has introduced scientific principles into day-to-day clinical decision-making. Not wanting to be left behind, anxious to prove to the world that it was as scientific and rigorous as the rest of medicine, psychiatry too fell under the spell of this revolution. As a result a technical model has come to replace what was once called the medical model.
It is a technical model in the sense that interventions for distress are no longer restricted to medical treatments, like drugs based in biological theories of disease (Thomas et al, 2012). Psychological interventions like cognitive behaviour therapy (CBT) have taken their place alongside medical interventions. A core feature of the technical model, whether medical or psychological, is the idea that these interventions are effective because they rectify specific faults in brain, or psychological, function. These faults in turn are believed to cause the distress that characterises psychiatric disorders. For example, experiences such as hearing voices or unusual beliefs are believed to be caused by over-activity in dopamine systems in specific areas of the brain. Neuroleptic drugs are thought to be effective because they reduce this over-activity. The fact that no evidence of dopamine over-activity has ever been found in the brains of people diagnosed with schizophrenia is neither here nor there, at least as far as justifying the use of these drugs is concerned. This is because the pharmaceutical industry became adept at manipulating drug trial data so as to convince everyone that these drugs were effective (Spielmans & Parry, 2009). As long as everyone ignored such deceit, or pretended it did not happen, a lack of scientific evidence to support the underlying model at work didn’t really matter. The evidence suggested that the drugs were effective, so what. However, the introduction of EBM in psychiatry has achieved something of great importance. It has drawn attention to the fact that these drugs do not work. In part this is because of the poor quality of the evidence used to justify the use of psychiatric drugs.
Concern about the poor quality of evidence for the use of neuroleptics in schizophrenia has been around for some time. Fifteen years ago a survey of the first 2000 trials of these drugs held on the Cochrane Schizophrenia Group’s register found that studies were too short (on average less than six weeks), contained too few patients (on average just 65), and were poorly reported (Thornley & Adams, 1998). Since then the situation has deteriorated. Recent evidence questions the quality of neuroleptic trials in schizophrenia, their effectiveness in the short-term (Bola 2006; 2012) and long-term (Harrow et al, 2012) management of the condition (see Robert Whittaker’s recent blog). Indeed, the evidence suggests that contrary to improving the prognosis of schizophrenia, the use of long-term neuroleptic drugs may actually make this worse (Baldessarini & Viguera, 1995; Viguera et al, 1997; Harrow et al, 2012). There is doubt, too, about the benefits of so-called second-generation (SG) neuroleptics over the first-generation (FG) drugs (Girgis et al 2011; Jones et al, 2006; Lieberman et al, 2005). A recent meta-analysis of 150 trials has confirmed the absence of consistent differences between SG and FG neuroleptics (Leucht et al, 2009).
Clozapine, the original ‘SG’ neuroleptic was withdrawn from use in 1975 after six patients died in Finland from agranulocytosis, a severe blood disorder. However, because laboratory studies found that clozapine’s apparent clinical potency did not correlate with its effect in blocking dopamine D2 receptors, and because it appeared to cause fewer neurological side effects, the argument gained ground that the drug had different mode of action from FG drugs, hence the adjective ‘atypical’. The revival of clozapine, together with the idea of ‘atypicality’ was born partly out of a hope that it would generate new pharmacological models of schizophrenia (Kerwin, 1995), and new drugs with less severe neurological side-effects. Thus the drug was re-introduced in Britain for the treatment of ‘treatment-resistant schizophrenia’ in 1990.
However, in a recent editorial in the British Journal of Psychiatry, Kendall (2011) writes as follows:
Where is the evidence that there is a unifying chemical structure for, or a clinically important difference in, the efficacy or effectiveness of ‘neuroleptics’, ‘major tranquillisers’, and ‘conventional’, ‘typical’, ‘atypical’, ‘first-generation’ and ‘second-generation’ antipsychotics? Is the ever changing terminology part of the fog generated by pharmaceutical companies to increase profits by the simple equation that ‘new is better’?
(Kendall, 2011: 266, emphasis added)
Professor Kendall is the director of the National Collaborating Centre for Mental Health at the Royal College of Psychiatrists. Through the National Institute for Health and Clinical Excellence (NICE) he is responsible for developing clinical practice guidelines for the National Health Service in England and Wales. The accumulating evidence that neuroleptic drugs are at best of limited value, and at worst cause long-term harm, have taken the wind out of the sails of the technical revolution in psychiatry. There is no place in the theory and practice of psychiatry for a discredited technical paradigm, grounded in naïve positivism and reductionism, and the morally bankrupt scientism peddled by the pharmaceutical industry. This is not a scientific revolution; it is a revolution of deceit.
So where do we go from here? One way forward is Joanna Moncrieff’s distinction between the disease-centred and drug centred model of how psychiatric drugs might be helpful for people who experience distress (Moncrieff, 2008). The disease-centred model, which can be seen as one version of the technical paradigm, maintains that drugs rectify specific abnormalities of brain function that are believed to be responsible for the experiences (symptoms, within this model) of psychiatric disorder. The therapeutic effects are assumed to relate to effects on abnormal brain states. The failure of this model is in part due to the fact that there is no convincing evidence that abnormal brain states cause the experiences of madness, at least not in the way that neuroscientific psychiatry currently believes.
The drug-centred model holds that psychiatric drugs cause abnormal brain states, and that any therapeutic benefits relate to impact of abnormal brain states on subjective experience. In other words they bring about a state of intoxication. An example of this is the use of alcohol to control social or other forms of anxiety. The drug-centred model has two advantages. First it uncouples the use of psychiatric drugs from unwarranted theories about how they might work. This opens up the way to a more participatory person-centred approach to using medication, what Joanna Moncrieff calls democratic drug treatment. Second, it is theory neutral as far as science is concerned, and this offers an opportunity to rethink what effects these drugs have on the mind/brain.
There is, however, an outstanding problem that any putative model of drug action must engage with, and that it is the potency of the placebo effect in psychiatry. Placebos, dummy tablets or injections, have been known to be effective in a wide range of conditions for many centuries. This suggests that the effectiveness of treatment in many areas of medicine, especially psychiatry, cannot be accounted for simply in terms of the biological properties of drugs. No matter how we, as psychiatrists or doctors, think that drugs work in biological terms, the use of medication must also be understood in human terms. As the medical anthropologist Daniel Moerman points out (2002) the placebo effect is a multi-layered phenomenon that stands at the interface between culture, biology, and the individual’s need for hope and meaning in the face of suffering and uncertainty. Whatever science follows in the wake of the revolution of deceit, if it is to be of clinical value in the practice of psychiatry, it has to find a way of engaging with the embodied complexity of the placebo response.
Baldessarini, R.J. & Viguera, A.C. (1995) Neuroleptic withdrawal in schizophrenic patients. Commentary in Archives of General Psychiatry, 52, 189 – 192.
Bola, J. (2006) Medication-Free Research in Early Episode Schizophrenia: Evidence of Long-Term Harm? Schizophrenia Bulletin 32, 2, 288–296.
Bola, J., Kao, D., & Haluk, S. (2012) Antipsychotic Medication for Early-Episode Schizophrenia Schizophrenia Bulletin, 38, 1, 23–25,
Harrow, M., Jobe, T. & Faull, R. (2012) Do all schizophrenia patients need antipsychotic treatment continuously throughout their life time? A 20-year longitudinal study. Psychological Medicine published online, 17 February 2012. Accessed at CJO 2012 doi:10.1017/S0033291712000220 28th February 2012.
Girgis RR, Phillips MR, Li X, Li K, Jiang H, Wu C, et al. (2011) Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year randomised clinical trial. British Journal of Psychiatry; 199: 281–8.
Jones PB, Barnes TRE, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al. (2006) Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the LatestAntipsychotic drugs in Schizophrenia Study (CUtLASS 1). Archives of General Psychiatry; 63: 1079–87.
Kendall, T. (2011) The rise and fall of the atypical antipsychotics. British Journal of Pychiatry, 199, 266–268.
Kerwin, R. (1995) Clozapine: back to the future for schizophrenia research. Lancet; 345: 1063–4.
Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a metaanalysis. Lancet; 373: 31–41.
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine; 353: 1209–23.
Moerman, D. (2002) Meaning, medicine and the ‘placebo effect’. Cambridge: Cambridge University Press.
Moncrieff, J. (2008) The Myth of the Chemical Cure: A Critique of Psychiatric Drug Treatment. Basingstoke, Palgrave
Spielmans, G. & Parry, P. (2009) From Evidence-based Medicine to Marketing-based Medicine: Evidence from Internal Industry Documents. Bioethical Inquiry DOI 10.1007/s11673-010-9208-8 (Accessed 29th Feb 2012)
Thomas, P., Bracken, P & Timimi, S. (2012) The Limits of Evidence-Based Medicine in Psychiatry. In Press, Philosophy, Psychiatry and Psychology.
Thornley, B. & Adams, C. (1998) Content and quality of 2000 controlled trials in schizophrenia over 50 years. British Medical Journal, 317;1181-1184.
Viguera, A., Baldessarini, R., Hegarty, J., van Kammen, D. & Tohen, M. (1997) Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 54, 49-55.