Current Status of Clinical Practice Guidelines in Schizophrenia

Schizophrenia is a chronic, often disabling illness, with onset in early adulthood affecting approximately 24 million people worldwide.^{1, 2} There is significant heterogeneity in the etiopathology, symptomatology, and course of the disease.³ Examples of “positive” symptoms include hallucinations, delusions, and disorganized speech, whereas negative symptoms include decreased emotional expression and lack of motivation. Early and sustained antipsychotic therapy and psychosocial treatment have demonstrated considerable efficacy in managing schizophrenia,⁴ with the prospect of recovery in some patients.

Evidence-based clinical practice guidelines can potentially enhance treatment quality and overcome existing disparities in the management of this serious disease.^{5, 6} They represent a solution to the difficulty of synthesizing and selecting relevant medical literature supported by scientific evidence.⁶ However, the methodological quality of schizophrenia guidelines varies, while lack of consistency across guidelines and inadequate adherence in the clinical setting can impact the quality of care and outcome.

Methodological Soundness of Schizophrenia Treatment Guidelines

From a global perspective, methodologically sound guidelines for the treatment of schizophrenia include those from the American Psychiatric Association (APA, 2004),⁷ the German Society of Psychiatry, Psychotherapy and Nervous Diseases (DGPPN, 2005),⁸ the National Institute for Clinical Excellence (NICE, 2014),⁹ the Patient Outcomes Research Team (PORT, 2009),¹⁰ and the Royal Australian and New Zealand College of Psychiatry (RANZCP, 2005).¹¹ While they all recommend treatment with antipsychotics, all 5 guidelines recommend different psychosocial interventions.

Analysis of guidelines from these bodies, using the validated Appraisal of Guidelines for Research and Evaluation (AGREE) instrument, indicated that average overall methodological quality was good (mean 75% of maximum possible score).⁵ The AGREE instrument assesses both the quality of reporting and the quality of the guideline development process, and provides an appraisal of the predicted validity of a guideline,.¹² Except for the NICE guidelines, all the guidelines analyzed were the latest versions. Scores for the “rigor of development” domain were high (mean 83) indicating that the guidelines were developed according to principles of evidence-based medicine.⁵ The selected guidelines also scored well on the “clarity and presentation” (mean 87) and “scope and purpose” (mean 98) domains.

With regard to content, the guidelines exhibited high consistency among most recommendations concerning selected core treatment decisions, including selection criteria for first antipsychotic (i.e. effect/side-effect profile, patients’ preference, and concomitant conditions), drug dosages, continuous antipsychotic maintenance treatment, non-response or treatment resistance, and psychosocial interventions.⁵ Discrepant areas included duration of maintenance drug treatment and first-line drug choice. The older guidelines — APA, DGPPN, and RANZCP — generally gave preference to “second-generation” (“atypical”) antipsychotics (except for clozapine), especially in first-episode patients, whereas the newer guidelines — NICE and PORT — recommended antipsychotics in general (except for clozapine; and olanzapine in PORT) reflecting evolving clinical evidence.

The large randomized trials conducted a decade ago, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS), found no significant advantages in efficacy favoring “second-generation” antipsychotics over “first-generation” agents, but data from The European First Episode Schizophrenia Trial (EUFEST) demonstrated advantages of some “second-generation” over “first-generation” antipsychotics.^13-16 Overall, these findings suggested the prospect for differential treatment decisions based on drug and patient profiles.