Clozapine resistant schizophrenia: Newer avenues of management

Table 3 Meta-analyses of antidepressant and mood stabilizer augmentation in clozapine-resistant schizophrenia

Ref.	Type of review	Details	Results
Antidepressants
Siskind et al[23], 2018	Meta-analysis	10 RCTs of fluoxetine, paroxetine, duloxetine, and mirtazapine augmentation	Some evidence for fluoxetine augmentation in reducing in overall symptom severity based on 1 high-quality RCT.
Correll et al[24], 2017	Meta-analysis	Analysis based on the earlier meta-analysis of Veerman et al[37]	No benefit of antidepressant augmentation on reduction in overall, positive, and negative symptom severity.
Veerman et al[37], 2014	Meta-analysis	4 RCTs of mirtazapine, duloxetine, and fluoxetine augmentation	No benefit of antidepressant augmentation on reduction in overall, positive, and negative symptom severity.
Sommer et al[30], 2012	Meta-analysis	4 RCTs of mirtazapine, citalopram, and fluoxetine augmentation	Some evidence for citalopram augmentation in reducing overall and negative symptom severity based on 1 RCT.
Mood stabilizers
Siskind et al[23], 2018	Meta-analysis	5 RCTs of valproate (n = 2), lamotrigine (n = 2), lithium (n = 1), and topiramate(n = 1) augmentation	Low-quality evidence for valproate and lithium augmentation in reducing total symptom severity. Reduction of positive and negative symptom severity by topiramate augmentation based on1 RCT.
Correll et al[24], 2017	Meta-analysis	Analysis based on the earlier meta-analysis of Veerman et al[37]	No benefit of lamotrigine and topiramate augmentation on reduction in overall, positive, and negative symptom severity.
Zheng et al[50], 2017	Meta-analysis	22 RCTs of valproate (n = 9), lamotrigine (n = 8), and topiramate (n = 4) augmentation	Significant benefits for valproate and topiramate in reducing total and positive symptom severity but based on low-quality studies. No effects on clinical response.
Zheng et al[48], 2016	Meta-analysis	4 RCTs of topiramate augmentation	Significant benefits of topiramate augmentation in reducing overall, positive, and negative symptom severity.
Veerman et al[49], 2014	Meta-analysis	6 RCTs of lamotrigine and 4 RCTs of topiramate augmentation	No benefit of lamotrigine and topiramate augmentation on reduction in overall, positive, and negative symptom severity.
Sommer et al[30], 2012	Meta-analysis	7 RCTs of lamotrigine (n = 4) and topiramate (n = 3) augmentation	Benefits of lamotrigine and topiramate augmentation for total and positive symptoms based on single RCTs that did not persist on further analysis.
Tiihonen et al[47], 2009	Meta-analysis	5 RCTs of lamotrigine augmentation	Evidence for benefit of lamotrigine augmentation in reducing overall, positive, and negative symptom severity.

RCT: Randomized controlled trial.