Augmentation of Antipsychotic Medications with Low-Dose Clozapine in Treatment-Resistant Schizophrenia—Case Reports and Discussion

Abstract

Treatment resistance in schizophrenia is often encountered in clinical practice, with clozapine usually recommended as the appropriate therapy. However, where clozapine proves ineffective or cannot be tolerated due to side effects, treatment options are limited. In patients within forensic mental health services, residual symptomatology often presents a barrier to discharge and can have lasting effects on prospects for rehabilitation as well as risk to self and others. This paper presents a review of the relevant literature and three cases of a novel approach, utilising clozapine in doses usually considered subtherapeutic, in combination with the primary antipsychotic treatment. In all three patients, it improved clinical efficacy as well as tolerability, resulting in improvement that allowed discharge from the forensic hospital.

Clozapine augmentation with long‐acting antipsychotic injections: A case series and systematic review

“…Duration of follow up varied from 3 months 14 to 3 years 21 and it was not reported in three study 16,19,24 and not applicable in one study 18 …”

“…Duration of follow up varied from 3 months 14 to 3 years 21 and it was not reported in three study 16,19,24 and not applicable in one study. 18 With regards to side effects, Bioque et al 20 reported that the combination of clozapine with LAI resulted in fewer side effects and was well tolerated.…”

“…We retrieved a total of 12 relevant articles which included two case reports, three case series and seven retrospective observational studies, four of which followed a mirrorimage design, representing a total of 195 patients (Table 1). Three studies were conducted in Turkey, 14,15 two in South Korea 16,17 two in Australia 18,19 and one in each of the following countries: Spain, 20 Canada, 21 Italy, 22 France 23 and the United States. 24 Both first-generation and second-generation antipsychotics were reported as adjunctive treatment to clozapine, although second-generation appeared more frequently.…”

Management of Treatment-Resistant Schizophrenia in a Patient With Epilepsy With Add on Low-Dose Clozapine—A Case Report

“…There are earlier reports of augmentation of antipsychotics with low-dose clozapine in the management of TRS. 4 Hence, clozapine was added to aripiprazole at the dose of 12.5 mg/d and gradually up-titrated to 75 mg/d over 2 weeks. The improvement in the positive symptoms was noted within a week of adding clozapine.…”

“…We did not consider monotherapy of clozapine considering the following: partial response with aripiprazole, clozapine associated seizures are dose-dependent and that monotherapy would have necessitated a higher dose of clozapine, which could have increased the risk of seizures further. There are earlier reports of augmentation of antipsychotics with low-dose clozapine in the management of TRS 4 . Hence, clozapine was added to aripiprazole at the dose of 12.5 mg/d and gradually up-titrated to 75 mg/d over 2 weeks.…”