Changing the Course of Schizophrenia-Predictors of Treatment Outcome Revisited

By Emsley, R.; Oosthuizen, P. et al. | South African Journal of Psychiatry, February 2007 | Go to article overview

Changing the Course of Schizophrenia-Predictors of Treatment Outcome Revisited


Emsley, R., Oosthuizen, P., Niehaus, D., Koen, L., Chiliza, B., South African Journal of Psychiatry


Multiple factors play a role in determining the outcome of schizophrenia. However, the role of these factors is poorly understood, and research findings so far have been inconclusive and sometimes contradictory. Various demographic and baseline clinical factors have been reported to be associated with treatment outcome. Also, early symptom reduction after initiation of antipsychotic therapy is closely related to later treatment response. However, associations as such do not necessarily imply predictive value, and none of these factors can be regarded as clinically useful in predicting treatment outcome. This article discusses selected aspects of treatment outcome and its prediction in schizophrenia, focusing particularly on early treatment response, ethnicity, neurological soft signs, and the predictive value of a discriminant functional analysis model utilising a combination of putative predictors. Such a model holds promise, and it is to be hoped that future refinements will lead to a clinically useful model for predicting outcome.

Schizophrenia is an incapacitating brain disease, having been described as arguably the worst illness affecting humankind--costly in personal, social and financial terms. (1) It imposes a disproportionately large economic burden on patients and their families, health care systems and society, because of its early onset, devastating effects, and usually lifelong course. (2)

Antipsychotics were introduced to clinical practice about 50 years ago, and have proved to be very effective in treating acute psychotic symptoms. However, in the long term the picture is very different, and the overall outcome of schizophrenia is poor. (3) In the majority of cases the illness is characterised by frequent relapses and rehospitalisations, (4) and severe social and occupational impairment. (3) Patients are frequently marginalised from society, unemployed (5) and at risk for suicide. (6)

Factors influencing treatment Outcome

Multiple factors may play a role in determining the outcome of the illness. For example, some patients are refractory to treatment from the outset, while others appear to acquire treatment refractoriness at some stage for reasons that are poorly understood. (7) In many cases, non- or partial adherence to medication may be responsible for a relapse, or for the persistence of residual psychotic symptoms. (8) Also, the presence of co-morbid disorders such as depression and substance abuse may complicate treatment and contribute to a poor overall outcome. (9)

Demographic and baseline clinical predictors of outcome

The factors determining treatment response are poorly understood, and research findings so far have been inconclusive and sometimes contradictory. Among other factors, a poorer response has been associated with male gender, history of obstetric complications, more severe positive symptoms, poorer attention at baseline, the development of parkinsonism during antipsychotic treatment, (10) extrapyramidal symptoms (EPSs) before antipsychotic exposure, (11) neurological soft signs, (12) cognitive impairment (13) and prolonged duration of untreated psychosis (DUP). (14) However, associations as such do not necessarily imply predictive value, and none of these factors can be regarded as clinically useful in forecasting treatment outcome. (15)

Early symptom reduction and treatment response

An alternative approach has recently produced promising results--early symptom reduction within days of initiation of antipsychotic treatment appears to closely parallel later treatment response, suggesting that this could be a useful predictor of outcome, either alone or in combination with other variables. While an association between early treatment response and treatment outcome has long been recognised, (16-23) it was not until recently that this topic has been studied in any detail. A meta-analysis (24) of the data of numerous clinical trials challenged the long-held belief that antipsychotic medication has a delayed onset of action, with evidence showing that the largest proportion of the response actually occurs within the first week of treatment. …

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