Clozapine resistant schizophrenia: Newer avenues of management

Table 5 Psychosocial augmentation strategies in clozapine-resistant schizophrenia

Ref.	Study/participants	Interventions	Results
Studies
Pinto et al[69], 1999	Single-blind RCT of 41 patients with TRS started on clozapine	CBT and social skills training vs supportive therapy for 6 mo.	Significant reductions in positive and negative symptom severity in the CBT group.
Buchain et al[70], 2003	Single-blind RCT of 41 patients with TRS started on clozapine	Occupational therapy and clozapine vs clozapine alone for 6 mo.	Significant improvements in the occupational performance and interpersonal relationships with OT.
Barretto et al[71], 2009	Single-blind RCT of 21 patients with CRS	CBT vs supportive treatment (“befriending”) for 21 wk.	Significant reductions in overall symptom severity and improvement in quality of life with CBT.
Morrison et al[75], 2018	Double-blind RCT of 425 patients with CRS	CBT vs usual treatment for 9 mo. Follow-up for 21 mo.	Significant reductions in PANSS scores with CBT at 9 mo but no differences at 21 mo.
Sensky et al[72], 2000; Valmaggia et al[73], 2005; Edwards et al[74], 2011	RCTs of patients with TRS (n = 48-90) including patients on clozapine or clozapine non-responders	CBT vs supportive treatment or clozapine alone or comparisons with combinations of CBT with other antipsychotics.	Significant reductions in positive, negative, and depressive symptom severity, improvement in clinical response and functioning with CBT; benefits at end of treatment usually maintained during follow-up.
Reviews
Ranasinghe et al[33], 2014	Systematic review	Review of the 2 CBT and 1 OT trial mentioned above.	Benefits of psychosocial interventions noted for overall symptom severity, quality of life, and social functioning.
Polese et al[68], 2019	Systematic review & meta-analysis	Review of all the above trials and meta-analysis of 4 RCTs including Morrison et al[75].	Benefits of psychosocial interventions noted for overall and positive symptom severity.

CBT: Cognitive-behavioural therapy; CRS: Clozapine resistant schizophrenia; PANSS: Positive and Negative Syndrome Scale; OT: Occupational therapy; TRS: Treatment resistant schizophrenia; RCT: Randomized controlled trial.