APA practice guideline: clozapine for treatment resistance, suicide risk, and aggression

“APA recommends (1B) that patients with treatment-resistant schizophrenia be treated with clozapine.” (opens the source at this quote in a new tab)
“APA recommends (1B) that patients with schizophrenia be treated with clozapine if the risk for suicide attempts or suicide remains substantial despite other treatments.” (opens the source at this quote in a new tab)
“APA suggests (2C) that patients with schizophrenia be treated with clozapine if the risk for aggressive behavior remains substantial despite other treatments.” (opens the source at this quote in a new tab)

“many patients would benefit from earlier consideration of clozapine initiation.” (opens the source at this quote in a new tab)

VA/DoD guideline: clozapine for treatment-resistant schizophrenia

“We recommend the use of clozapine for individuals with treatment-resistant schizophrenia.” (opens the source at this quote in a new tab)

NICE guideline: clozapine after two antipsychotic drugs

“Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least 2 different antipsychotic drugs. At least 1 of the drugs should be a non-clozapine second-generation antipsychotic.” (opens the source at this quote in a new tab)

Australian and New Zealand GRADE guideline: clozapine and electroconvulsive therapy in treatment resistance

“We recommend that people with treatment-resistant schizophrenia should be offered clozapine.” (opens the source at this quote in a new tab)
“We suggest that people with treatment-resistant schizophrenia may be offered electroconvulsive therapy.” (opens the source at this quote in a new tab)

FDA-approved indications and restriction of use

“Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.” (opens the source at this quote in a new tab)
“Because of the risks of severe neutropenia and of seizure associated with its use, CLOZARIL should be used only in patients who have failed to respond adequately to standard antipsychotic treatment.” (opens the source at this quote in a new tab)
“Reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior.” (opens the source at this quote in a new tab)

Boxed warning

“WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS” (opens the source at this quote in a new tab)
“CLOZARIL has caused severe neutropenia, which is associated with an increased risk of serious and fatal infections.” (opens the source at this quote in a new tab)

Efficacy in treatment-refractory schizophrenia: meta-analysis of randomized trials

“Twenty-one papers with 25 comparisons were included. The number needed to treat was 9.” (opens the source at this quote in a new tab)
“Clozapine is superior for treatment-refractory disorder but if there is no response by 6 months medications with lower adverse reactions should be considered.” (opens the source at this quote in a new tab)

Response rate in treatment-resistant schizophrenia

“Overall, 40.1% (95% confidence interval [CI], 36.8%-43.4%) responded, with a mean reduction in PANSS of 22.0 points (95% CI, 20.9-23.1), a reduction of 25.8% (95% CI, 24.7%-26.9%) from baseline.” (opens the source at this quote in a new tab)
“A 40% response rate to clozapine suggests that 12% to 20% of people with schizophrenia will be ultra-resistant.” (opens the source at this quote in a new tab)

Real-world rehospitalization and treatment failure

“Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine.” (opens the source at this quote in a new tab)

OPTiMiSE: clozapine after non-remission on amisulpride and olanzapine

“Of the 40 patients who were not in remission after 10 weeks of treatment, 28 (70%) started on clozapine; 18 (64%) patients completed the 12-week treatment, and five (28%) achieved remission.” (opens the source at this quote in a new tab)

Underuse of clozapine

“Guidelines worldwide recognize clozapine as the most effective treatment option for TRS, but clozapine is underused due to various barriers.” (opens the source at this quote in a new tab)