No abstract

Nonadherence to antipsychotic medications for the treatment of schizophrenia is a widely recognized concern, leading to poorer clinical outcomes and higher treatment costs. Long-acting injectable (LAI) antipsychotics offer an extended dosing interval option for patients, although the current options may require an oral overlap at initiation. Aripiprazole lauroxil is an LAI that offers multiple dosing options but requires oral treatment overlap during initiation for the first 21 consecutive days. As an alternative to oral overlap, a novel nano-crystalline milled dispersion delivery system of aripiprazole lauroxil was recently approved as a one-day regimen to be added to aripiprazole lauroxil treatment.

Objective Determine if clozapine can be safely utilized in a population of psychiatric patients with current or a history of benign neutropenia. Method A single-center, retrospective chart review was conducted in an inpatient psychiatric hospital. Patients included had benign neutropenia prior to receiving clozapine and received clozapine using modified monitoring guidelines. All available laboratory values for absolute neutrophil count (ANC) before clozapine initiation and during treatment were evaluated. The primary endpoint was the difference in ANC after initiation of clozapine compared to before clozapine treatment. Results A total of 26 patients were reviewed. Mean age was 34 years at clozapine initiation. The majority were African-American (73%), with more males than females (73% vs. 27%). The mean lowest ANC value was not significantly different after clozapine initiation compared to before (1.5 and 1.4×103 cells/mm3, respectively; p=0.22). There were no cases of agranulocytosis (ANC <0.5 ×103 cells/mm3) and no patients were discontinued for falling below limits set by modified guidelines. There were fewer occurrences of mild neutropenia (ANC <2.0×103 cells/mm3) after clozapine initiation than before (16% and 31.4%, respectively; p<0.001). There were also fewer occurrences of moderate neutropenia (ANC <1.5×103 cells/mm3) with 2.1% after clozapine and 13.3% before (p<0.001). Occurrence of ANC <1.0×103 cells/mm3 did not differ (0.4% before, 0.3% after, p=0.79). Conclusion Twenty-six patients with benign neutropenia were safely treated with clozapine. Their pre-clozapine neutropenia did not predict increased risk for agranulocytosis with clozapine. Patients had significantly fewer episodes of mild and moderate neutropenia after receiving clozapine compared to before.

One of clozapine's unrecognized potential side effects is renal insufficiency and nephritis. Although most clinicians are aware of the possibility of clozapine-induced myocarditis, less is known about other inflammatory disorders due to clozapine treatment. This patient was started on lithium and clozapine within 4 days of each other although lithium was discontinued after 7 days due to tremor. Routine labs showed an increase in serum creatinine, which was initially attributed to the recent lithium. However, the patient's kidney function continued to worsen, requiring discontinuation of clozapine despite a robust response to a low dose. Several years later, the patient's kidney function improved but has not returned to baseline. This literature review and case report illustrates the similarities in diagnostic presentation of clozapine-associated renal insufficiency as well as potential risk factors. More research should be conducted into the role concomitant sodium valproate and/or lithium play in the risk of clozapine-associated renal insufficiency.