Elias Wagner1, Lisa Löhrs1, Dan Siskind2,3, William G Honer4, Peter Falkai1, Alkomiet Hasan1. 1. 1 Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany. 2. 2 School of Medicine, University of Queensland, Brisbane, QLD, Australia. 3. 3 Metro South Addiction and Mental Health Service, Brisbane, QLD, Australia. 4. 4 Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada.
Abstract
BACKGROUND: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse. AIMS: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice. METHODS: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified. RESULTS: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only. CONCLUSION: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
BACKGROUND: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse. AIMS: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice. METHODS: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified. RESULTS: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only. CONCLUSION: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
Authors: Elias Wagner; John M Kane; Christoph U Correll; Oliver Howes; Dan Siskind; William G Honer; Jimmy Lee; Peter Falkai; Thomas Schneider-Axmann; Alkomiet Hasan Journal: Schizophr Bull Date: 2020-12-01 Impact factor: 9.306
Authors: C U Correll; Ofer Agid; Benedicto Crespo-Facorro; Andrea de Bartolomeis; Andrea Fagiolini; Niko Seppälä; Oliver D Howes Journal: CNS Drugs Date: 2022-06-27 Impact factor: 6.497