Where to Position Clozapine: Re-Examining the Evidence

Abstract

Objective: To review clozapine's position in treatment algorithms for schizophrenia.Method: Clozapine's status is reviewed in the context of its initial discovery and unique clinical and (or) pharmacological profile, withdrawal and link with hematologic concerns, reintroduction with monitoring guidelines, prototype for atypicality, positioning in treatment algorithms, and current evidence regarding efficacy, effectiveness, and side effects. Results:The hematologic monitoring implemented with clozapine's reintroduction here in North America has proven successful in preventing clozapine-related deaths secondary to agranulocytosis. While its other side effects are not without concern, present evidence does not link clozapine to increased mortality rates; indeed, it appears better than other antipsychotics in this regard. Moreover, its clinical superiority compared with all other antipsychotics has been confirmed both in efficacy and in effectiveness trials.Conclusions: Schizophrenia continues to represent a treatment challenge, with many people demonstrating suboptimal response and poor functional outcome. Clozapine is routinely positioned as a third-line treatment in schizophrenia, but in light of existing evidence this warrants re-examination.Can J Psychiatry. 2010;55(10):677-684. Clinical Implications· Although clozapine has demonstrated superiority to other antipsychotics in refractory schizophrenia, it remains underprescribed and delayed in its use.· A large body of recent data, in combination with current safety measures, confirms that clozapine-induced agranulocytosis and related deaths are very rare.· Clozapine's unique clinical profile in refractory schizophrenia challenges delayed access to its use. Limitations· The data in this review are relevant and applicable only in the countries where clozapine safety measures are in place. · Clozapine's clinical superiority appears specific to refractory schizophrenia. · Use of clozapine earlier than third-line treatment requires a re-evaluation of how refractory schizophrenia is currently defined.

Obesity correlates with fewer symptoms in schizophrenia treated with long-term clozapine: Gender difference

“…Clozapine is commonly used for treatment-refractory schizophrenia in China (Tang et al, 2008), because it has fewer extrapyrimidal side effects and better efficacy than standard antipsychotics (Agid et al, 2010;Nielsen et al, 2011). However, clozapine produces more weight gain than other antipsychotics (Pramyothin and Khaodhiar, 2010;Asenjo Lobos et al, 2010), while weight gain may be associated with improvement in psychopathology (Meltzer et al, 2003;Ascher-Svanum et al, 2005).…”

Update on the Adverse Effects of Clozapine: Focus on Myocarditis

“…Benefits of Clozapine Use in the "Real World" Clinical Practice. Adapted from [13][14][15][16][17] Proven efficacy in refractory schizophrenia Efficacy on both positive and negative symptoms of refractory schizophrenia Efficacious in reducing aggressive behaviour, hostility and excitement in schizophrenia Efficacious in reducing the comorbid use of alcohol and drugs in patients with schizophrenia, possibly by a reduction in the craving Efficacious in reducing suicidality in schizophrenia Efficacious in severe mood disorders Efficacious in drug-induced psychosis in Parkinson's disease, without worsening Parkinsonism Efficacious in reducing drug-induced Tardive Diskynesia it should be recommended to begin clozapine treatment as inpatients, for the purposes of increased clinical surveillance [55]. In fact, as stated by Ronaldson et al [56], this strategy means that documentation of symptoms, vital signs and pathology results is more comprehensive than would be the case with patients initiated in the community.…”

“…To date, in terms of evidences and literature proceedings, clozapine is the acknowledged treatment of choice for patients with severe treatmentrefractory schizophrenia [9][10][11][12][13].…”

Monitoring Clozapine Adverse Effects Calls for the Integration of Protocol and Good Clinical Practice

“…1 It has even been argued that clozapine should be considered the first-choice treatment of a first-episode psychosis. 2 In addition, clozapine appears to be more beneficial than other antipsychotics in the treatment of negative and cognitive symptoms. 3,4 Finally, clozapine has clearly been shown to be the most effective pharmacologic treatment currently available for positive symptoms in psychotic patients.…”