Why Are the Outcomes in Patients With Schizophrenia So Poor?

Robert B. Zipursky, MD

Despite many advances in the treatment of schizophrenia over the past 50 years, the outcomes for many patients remain poor. Studies of patients receiving treatment for a first episode of schizophrenia have been very consistent in demonstrating that a substantial majority will achieve a remission of psychotic symptoms within the first year of treatment.1 In the long-term, however, it is estimated that only 1 in 7 will meet criteria for recovery.2 The findings of positive short-term outcomes and poor long-term outcomes could easily be reconciled by accepting that schizophrenia is a brain disease that is progressive in nature.

Is Schizophrenia a Progressive or a Stable Brain Disease?

Several studies have demonstrated significant cognitive deficits in patients with schizophrenia at the time of the first episode.3,4 These deficits, however, appear to remain stable or improve across time after the first episode rather than showing deterioration.5-7

The structural brain abnormalities reported in patients with schizophrenia have also been described in patients experiencing their f​irst episode of psychosis.1 Longitudinal studies of magnetic resonance imaging (MRI) brain volumes following a first episode of psychosis have been inconsistent in demonstrating loss of tissue volumes over time.8-11 It has become increasingly clear that exposure to antipsychotic medications is associated with brain changes on MRI.12-15 Alcohol and cannabis use, smoking, and stress may also contribute to the differences found between patients and controls over time.1 As a result, it remains unclear whether the brain changes reported in patients with schizophrenia over time reflect the underlying pathophysiology of schizophrenia or potentially reversible effects of other non-illness-related factors.

Longitudinal outcome studies also provide little support for schizophrenia being a progressive deteriorating illness. A number of studies have reported that 70% to 80% of patients will achieve a remission of symptoms in their first year of treatment.16-18 With comprehensive care, it is thought that a comparable percentage of patients are able to sustain remission at least over the first decade of follow-up.19 It is clear that without antipsychotic medication the relapse rate following a first episode of schizophrenia approaches 80% in the first year and 100% after 3 years; with maintenance antipsychotic medication, the 1-year relapse rate for remitted patients is likely in the range of 0% to 5%.20 Relapse, while extremely common, should not be understood as an inevitable part of the course of schizophrenia but rather as a direct reflection of poor adherence to treatment.

What Factors Account for Poor Outcomes?

It is estimated that only 25% to 40% of individuals with schizophrenia receive stable ongoing treatment.21 This quite likely reflects both the lack of adequate services and the challenges in engaging patients in ongoing treatment.22 Of those who receive treatment, an estimated 20% to 30% do not respond well to antipsychotic medications.23 Among those who respond well to antipsychotic medication, nonadherence to medication is thought to be a problem for approximately 50% of patients24 and very likely accounts for the high rates of relapse and rehospitalization. Many individuals with schizophrenia are further disabled by long-standing deficits in cognitive and social functioning, substance use disorders, comorbid psychiatric disorders such as mood and anxiety disorders, and many years of poor functioning preceding the onset of psychosis and initiation of treatment. The poverty, poor housing, and inadequate social support that many individuals encounter further compound their difficulties in achieving more positive outcomes.


Despite high rates of symptomatic remission following a first episode of psychosis, achieving long-term functional and symptomatic recovery is an elusive goal for the large majority of individuals. Evidence to date does not support the view that these disappointing outcomes can be explained by progressive deterioration in brain structures or cognitive functioning. Nor do relapses appear to be an inevitable feature of the long-term course of treated schizophrenia. The cumulative impact of poor access to treatment, poor engagement in ongoing care, poor treatment response, and poor adherence most likely accounts for the poor outcomes so frequently observed; substance abuse, comorbid psychiatric disorders, cognitive deficits, together with the negative impact of multiple determinants of health, further limit the achievement of recovery for most people with schizophrenia. Future clinical and research efforts will need to be devoted to developing approaches that will address the full range of determinants of outcome if recovery from schizophrenia is to be achieved.

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John W. Newcomer, MD

Robert B. Zipursky, MD

Department of Psychiatry and Behavioural Neurosciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

This Brief Report is derived from the roundtable meeting “Understanding the lifetime course of schizophrenia: a longitudinal perspective on neurobiology to promote better outcomes and recovery,” which was held October 15, 2013. The author acknowledges Healthcare Global Village for editorial assistance in developing the manuscripts.

The meeting, manuscript preparation, and dissemination of this brief report were supported by Otsuka America Pharmaceutical, Inc., and Lundbeck. All faculty received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of the manuscripts.

Faculty Disclosure

Dr Zipursky received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of this manuscript and, in the last year, has received consulting fees from Lundbeck and Amgen and research support from Roche.


The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the publisher, the American Society of Clinical Psychopharmacology, Healthcare Global Village, or the commercial supporters.


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