A systematic review of evidence-based treatment for individuals with treatment-resistant schizophrenia and a suboptimal response to clozapine monotherapy

Background: Currently, only clozapine is licensed for ‘treatment-resistant schizophrenia’ (TRS). However, ad hoc clozapine augmentation strategies are frequently resorted to, without clear guideline from evidence-based medicine, for individuals with a suboptimal response to clozapine monotherapy.Aims: To identify the optimal evidence-based clozapine augmentation regime with either pharmacological or psychosocial interventions, or a combination of pharmacological and psychosocial approaches.Method: Systematic analysis of randomised controlled trials of clozapine monotherapy versus clozapine/adjunctive medication and clozapine/psychosocial adjunctive therapiesResults: No trial was identified investigating clozapine augmentation with both psychosocial and pharmacological strategies. Six trials investigating clozapine augmentation with various medication, such as Lamotrigine, Risperidone, Aripiprazole and Sulpiride, were identified. These trials reported some effects on overall symptoms. Two trials of clozaoine augmentation with Cognitive Behavioural Therapy found positive effects on overall mental state and discussed an improved quality of life. One trial on Occupational Therapy-clozapine augmentation reported improved occupational performance and interpersonal relationships.Conclusion: Our review findings suggest psychosocial intervention augmentations are potentially effective treatments for service users with TRS. Less conclusive results are identified from the many pharmacological augmentation strategies. Longer and larger trials are required to demonstrate long-term effects.Declaration of Interest: None