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At last, a promising alternative to antipsychotics for schizophrenia

Imagine that, after feeling unwell for a while, you visit your GP. “Ah,” says the doctor decisively, “what you need is medication X. It’s often pretty effective, though there can be side-effects. You may gain weight. Or feel drowsy. And you may develop tremors reminiscent of Parkinson’s disease.” Warily, you glance at the prescription on the doctor’s desk, but she hasn’t finished. “Some patients find that sex becomes a problem. Diabetes and heart problems are a risk. And in the long term the drug may actually shrink your brain … ”

This scenario may sound far-fetched, but it is precisely what faces people diagnosed with schizophrenia. Since the 1950s, the illness has generally been treated using antipsychotic drugs – which, as with so many medications, were discovered by chance. A French surgeon investigating treatments for surgical shock found that one of the drugs he tried – the antihistamine chlorpromazine – produced powerful psychological effects. This prompted the psychiatrist Pierre Deniker to give the drug to some of his most troubled patients. Their symptoms improved dramatically, and a major breakthrough in the treatment of psychosis seemed to have arrived.

Many other antipsychotic drugs have followed in chlorpromazine’s wake and today these medications comprise 10% of total NHS psychiatric prescriptions. They are costly items: the NHS spends more on these medications than it does for any other psychiatric drug, including antidepressants. Globally, around $14.5bn is estimated to be spent on antipsychotics each year.

Since the 1950s the strategy of all too many NHS mental health teams has been a simple one. Assuming that psychosis is primarily a biological brain problem, clinicians prescribe an antipsychotic medication and everyone does their level best to get the patient to take it, often for long periods. There can be little doubt that these drugs make a positive difference, reducing delusions and hallucinations and making relapse less likely – provided, that is, the patient takes their medication.


Unfortunately, dropout rates are high. This is partly because individuals sometimes don’t accept that they are ill. But a major reason is the side-effects. These vary from drug to drug, but they’re common and for many people are worse than the symptoms they are designed to treat.

In addition, antipsychotics don’t work for everyone. It is estimated that six months after first being prescribed them, as many as 50% of patients are either taking the drugs haphazardly or not at all.

The conventional treatment for this most severe of psychiatric illnesses, then, is expensive, frequently unpleasant, and not always effective even for those who carry on taking the drugs. But it is what we have relied upon – which helps to explain why the results of a clinical trial, recently published in The Lancet, have generated so much interest and debate.

A team led by Professor Anthony Morrison at the University of Manchester randomly assigned a group of patients, all of whom had opted not to take antipsychotics, to treatment as usual (involving a range of non-pharmaceutical care) or to treatment as usual plus a course of cognitive therapy (CT). Drop-out rates for the cognitive therapy were low, while its efficacy in reducing the symptoms of psychosis was comparable to what medication can achieve.

So what exactly is CT for schizophrenia? At its core is the idea that the patient should be encouraged to talk about their experiences – just as they would for every other psychological condition. Psychosis isn’t viewed as a biological illness that one either has or does not have. Instead, just like every other mental disorder, psychotic experiences are seen as the severest instances of thoughts and feelings – notably delusions and hallucinations – that many of us experience from time to time.

Working together, the patient and therapist develop a model of what’s causing the experiences, and why they’re recurring. These factors will vary from person to person, so what is produced is a bespoke account of the individual’s experience, which is then used to guide treatment. For example, a person so worried by paranoid fears that they won’t set foot outside might be helped to trace the roots of their anxiety to past experiences; to gradually test out their fearful thoughts; and to learn to manage their anxiety while getting on with the activities they enjoy. An individual troubled by hearing voices will be helped to understand what’s triggering these voices, and to develop a more confident, empowering relationship with them.

These are early days. Nevertheless, most of the meta-analyses of CT’s efficacy for psychosis, when added to standard treatment, have indicated definite (albeit modest) benefits for patients, with the latest showing that CT is better than other psychological treatments for reducing delusions and hallucinations. The latest guidelines from the UK’s National Institute for Health and Care Excellence (Nice) recommend it for those at risk of psychosis and, when combined with medication, for people with an ongoing problem.

But not everyone is convinced, and although the research published in The Lancet is encouraging, it was small scale. CT for psychosis is still evolving, and we think that evolution should prioritise three key areas.

First, we must focus on understanding and treating individual psychotic experiences. As we’ve reported in a previous post, there is increasing reason to doubt the usefulness of the diagnosis “schizophrenia”. The term has been used as a catch-all for an assortment of unusual thoughts and feelings that often have no intrinsic connections, and aren’t qualitatively different from those experienced by the general population. Each psychotic experience may therefore require a tailored treatment.

Second, we must build on the recent transformation in understanding the causes of psychotic experiences, taking one factor at a time (insomnia, say, or worry), developing an intervention to change it, and then observing the effects of that intervention on an individual’s difficulties.

And finally, we must listen to what patients want from their treatment – for example, by focusing on improving levels of wellbeing, which tend to be very low among people with schizophrenia.

What about costs compared with drug treatment? A course of CBT is typically just over £1,000, but if it leads to a reduction in the amount of time patients spend in hospital and their use of other services, or a return to work, then it easily pays for itself.

The Nice guidance on psychosis and schizophrenia, updated this year, is unequivocal:

“The systematic review of economic evidence showed that provision of CBT to people with schizophrenia in the UK improved clinical outcomes at no additional cost. This finding was supported by economic modelling undertaken for this guideline, which suggested that provision of CBT might result in net cost savings to the NHS, associated with a reduction in future hospitalisation rates.”

If the real promise of cognitive therapy can be fulfilled, we may at last have a genuinely effective, relatively cheap, and side-effect-free alternative to antipsychotics for those patients who don’t wish to take them. Watch this space.

Daniel and Jason Freeman are the authors of Paranoia: the 21st Century Fear. Daniel is a professor of clinical psychology and a Medical Research Council Senior Clinical Fellow at the University of Oxford, and a Fellow of University College, Oxford. Twitter: @ProfDFreeman. Jason is a psychology writer. Twitter: @JasonFreeman100