Clinical Experience With Intramuscular Clozapine.

Benedikt Munzar,Boris Nemets

doi:10.7759/cureus.18267

Abstract

Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many refuse to accept oral clozapine therapy. Intramuscular (IM) clozapine represents a convenient alternative for their treatment. The aim of this review is to summarize studies investigating IM clozapine administration. When initially developed, clozapine was also provided as an IM formulation, but the manufacturer later discontinued its production. Recently, IM clozapine became again available as an unlicensed product distributed by the Dutch company Apotheek A15. The use of IM clozapine has been reported in older studies on clozapine’s adverse effects. It has also been described in detail in 5 more recent and generally smaller (n = 7 - 59) retrospective studies in patients refusing to take oral clozapine. In addition, its administration has been noted in 5 case reports. IM clozapine has been used at approximately ½ of the dose of oral clozapine due to pharmacokinetic considerations. It has been used in doses of up to 500 mg per day and for up to 99 days of treatment. The majority of patients (between 60 and 100%) were successfully transitioned to oral clozapine within a few days of IM treatment, and improvement in their condition was sustained during the long-term follow-up. Side effects of IM clozapine were similar to those of oral clozapine, but its sedative and cardiovascular effects (hypotension and tachycardia) had faster onset following IM administration. After long-term use, clozapine injections lead to local swelling and to the formation of painful nodules in some patients. In summary, IM clozapine may facilitate successful transition to oral clozapine in most patients, and it definitely represents a valuable tool for addressing refusal of oral clozapine in patients with treatment-refractory schizophrenia. More studies, especially focused on its safety, are, however, needed to better understand the limitations of this novel treatment approach.

Highlights

BackgroundClozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, providing clear benefits in about 60% of subjects [1,2,3]
Many treatment-refractory patients are refusing to accept oral clozapine therapy, with the percentage of noncompliance estimated at about 20% [2, 4] and are deprived of this life-changing treatment. In addition to those refusing oral treatment, there are subgroups of patients who are unable to accept oral formulations of clozapine due to swallowing difficulties or other GI problems [5,6], cannot receive oral clozapine due to perioperative status [7], are unable to benefit from oral clozapine due to catatonia precipitated by clozapine discontinuation [8] or caused by other factors responsive to clozapine treatment [9]
We summarize all available reports on intramuscular clozapine administration and address reported efficacy as well as potential side effects and risks associated with this clozapine formulation

Summary

Introduction

BackgroundClozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, providing clear benefits in about 60% of subjects [1,2,3]. Many treatment-refractory patients are refusing to accept oral clozapine therapy, with the percentage of noncompliance estimated at about 20% [2, 4] and are deprived of this life-changing treatment. Clozapine may be mixed with food offered to non-consenting subjects without their knowledge [10] This option is, very unreliable and is considered unethical by most psychiatrists [11]. That option requires restraints and is traumatizing to both the patient and attending staff and is reserved only for the most complicated cases where no other alternative exists [14] Alternative delivery routes, such as nasal delivery [15] and transdermal delivery [16,17], are in development but are not yet clinically available. Clozapine has been delivered via intravenous infusion but only under a research setting [18]

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