Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the ‘real world’

Abstract

Pai NB, Laidlaw M, Vella S‐C. Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia (SZ) in the ‘real world’. Objective: Refractory schizophrenia (SZ) affects approximately 30% of people with SZ. Clozapine (CLZ) is the gold standard treatment; however, there are still patients who are non‐responsive or partially responsive to treatment. Although a lack of evidence exists in reality, these patients are treated with a combination of agents in addition to CLZ. Therefore, this article reviews the prevalence of the augmentation of CLZ with additional agents. Method: This study was cross‐sectional; physicians in a region of Australia in May 2011 were contacted to provide details of their patients on CLZ and any additional agents. The data set consists of 84 patients. Results: The majority of the patients 84.5% were taking at least one additional agent. Of those taking additional agents, they derived from the following classes’ antipsychotics (72%), antidepressants (30%), mood stabilisers (17%), antimetabolic agents (13%), benzodiazepines (7%), anticholinergics (4%) and miscellaneous agents (12.5%). Conclusion: It is apparent that CLZ is routinely augmented with other agents despite the lack of an evidence base. However, concerning was the lack of augmentation with antimetabolic agents despite the paucity of literature reporting the detrimental impact of antipsychotic treatment upon patients metabolic indices. The findings are discussed in the context of the current recommendations and empirical literature.

Prevalence of multiple antipsychotic use and associated adverse effects in Australians with mental illness

“…8,29 In these populations, the prevalence of dual antipsychotic use ranged from 20% among those with treatment resistant psychosis to 61% among clozapine users. 3,8,30 The High Impact Psychosis Survey found 15% of patients reported taking two atypical antipsychotics concurrently. 3 Use of three antipsychotic agents concurrently was reported at between 5 and 7% among people using clozapine.…”

“…3 Use of three antipsychotic agents concurrently was reported at between 5 and 7% among people using clozapine. 3,30 Two Australian studies assessed antipsychotic doses among people receiving treatment via a community mental health service. 8,29 In a Sydney, NSW study of 56 people who received a Home Medicines Review, 29% took one or more antipsychotic medication at a dose exceeding the recommended maximum dose.…”

Clozapine use pattern in persons with and without treatment for Parkinson's disease in real-world conditions: a naturalistic study in a community-based sample

“…Antipsychotic augmentation is recommended by most clinical guidelines in ultraresistant schizophrenia , although data drawn from randomized controlled trials suggest that antipsychotic polytherapy confers limited benefit in this condition . In naturalistic conditions, concurrent prescription of another antipsychotic is relatively frequent in clozapine treatment . However, very few studies have explored the pattern of antipsychotic switching or addition in clozapine users .…”

Evaluation of the Incidence of Leukopenia and Agranulocytosis in Patients Receiving Combined Clozapine and Other Antipsychotics

“…The data obtained through a ten year-follow-up study showed that mortality rate increased by 2-3 times in cases where multiple antipsychotic medications were used in combination (23). In cases where high-doses of clozapine cannot be applied due to inadequate response to clozapine or its side effects, combination of clozapine with typical or atypical antipsychotics is generally applied in clinical practice (13)(14)(15). The use of clozapine with other antipsychotics (amisulpride, risperidone, quetiapine, olanzapine, haloperidol, paliperidone, aripiprazole) has been reported to improve the efficiency of the treatment (24)(25)(26)(27).…”

“…There have been recent case reports indicating that other atypical antipsychotic medications also lead to leukopenia and agranulocytosis like clozapine (10)(11)(12). In cases where high-dose clozapine cannot be used due to an inadequate response to antipsychotic treatment or its side effects, it has been reported that administration of clozapine with typical and atypical antipsychotics is a method of treatment widely used in clinical practice (13)(14)(15). Due to the risk of agranulocytosis, periodic follow-up white blood cell counts should be performed in patients who use clozapine.…”