Long term outcome of treating schizophrenia

Schizophrenia is one of the most disabling of mental illnesses, affecting one in 100 people in their lifetime, some 80% of whom will experience chronic or relapsing symptoms.¹ What do we really know about its long term treatment?

The guidelines on schizophrenia issued by the National Institute for Clinical Excellence (NICE) describe antipsychotic drugs as “an indispensable treatment option for most people in the recovery phase of schizophrenia,”² and a recent meta-review of depot antipsychotic injections considered them to be an effective maintenance treatment.³ Conventional antipsychotics (those acting via dopamine blockade, such as chlorpromazine or haloperidol), introduced in the 1950s, increased the proportion of patients who improved clinically noticeably from 35.4% to 48.5%.⁴ Because of their mode of action these drugs generated serious side effects, such as parkinsonism or hyperprolactinaemia; hence new generation, atypical antipsychotic agents (such as clozapine, olanzapine, risperidone, quetiapine) have been used (and sold) increasingly since the mid-1990s.

Acting more via 5HT blockade, but with interestingly variable biochemical profiles, these newer drugs have been shown to be as effective as the conventional drugs in treatment and relapse prevention.⁵ But they have yet to establish their longer term credentials in an illness that is usually lifelong.

The nature of schizophrenia as an illness (delusions, hallucinations, limited insight) leads to some 80% of patients relapsing within two years of a treated first episode (usually because of non-adherence to continuing medication), and only one in six patients remaining relapse free (and not needing medication) 10-15 years later.⁶ However, recent critiques have shown that recovery and readmission rates in schizophrenia before 1950 were no different⁷ and that antipsychotic agents might even do more harm than good.⁸ Thus the marked decline in the numbers of patients in asylums, from the mid-1950s (in the United Kingdom from some 150 000 in 1956 to under 40 000 in 1990) is usually attributed, at least in part, to effects of the medication. But this decline could equally be seen as socially generated via fiscal policies and community care programmes.⁸ Enhanced biological vulnerability to psychotic relapse might even be a result of the brain being made supersensitive to dopamine,⁹ medication thus acting as a double edged sword, relieving the symptoms of illness but creating an increased potential for relapse once drugs are discontinued.

The World Health Organization's studies of relapse in the 1960s and 1970s showed better outcomes of schizophrenia, surprisingly, in developing countries than in industrialised ones, with over 60% of patients in poor countries asymptomatic after five years compared with only 18% in rich countries.¹⁰ This finding was generally attributed to better social acceptance and support in agrarian communities, but it may have been related to less use of mainstream antipsychotic agents, and continued use of medication correlating with poorer outcome.⁸

Such criticisms rely on a somewhat selective viewing of the literature; more severe illnesses usually require higher doses of medication, thus creating the illusion that the medication creates the severity. More recent appraisals have identified other factors. These include the fact that we now have better definitions of what is and is not schizophrenia. Studies have identified the importance of the family in psychoeducational approaches,¹ especially the need to counter the relapse inducing effects of high expressed emotion (the term used to describe families having persistently critical or hostile attitudes towards their schizophrenic kin). We also know that long term studies show that patients with schizophrenia tend to stabilise anyway after about five years through the natural alleviations of the disease and increasing age and maturity.¹¹ Also we no longer have the large, backward, “demented,” long stay asylum population,⁴ and there is agreement that the duration of untreated illness with active symptoms tends to predict the patient's ability to recover—the shorter the better—and that relapse rates can be reduced by continuing with antipsychotics for at least two years after recovery.¹

But there are no grounds for complacency, even with the new atypical agents. These may have their own longer term problems, weight gain and diabetes being the most obvious so far.¹² Treatment with any therapies, should include careful review of physical health, medication dosages, and consideration of graduated withdrawal. Such careful assessments are, of course, made difficult by the patients one cannot research: those who are non-compliant, who use alcohol or illegal drugs damagingly, and who constantly evade even the most diligent community teams.

The history of schizophrenia has shown that it can be a devastating illness and that medication has created at least a cohort of patients more coherent and articulate in describing their experience. But an outstanding need remains for continuity of care, adequately resourced, and for long term studies of outcome and treatments over decades rather than a few months. Such research fits poorly with the short term pressures of the research assessment exercise, drug company marketing policies, or career advancement.