1. Loxapine Substitution for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review
Seema Jain1, Rebecca Andridge2, Jessica Hellings3
The Ohio State University College of Medicine, Columbus, OH; 2. The Ohio State University College of Public Health, Columbus, OH; 3. The Ohio State University Nisonger Center, Columbus, OH
Introduction
Results
Conclusions
Atypical antipsychotics are widely used to treat irritability and aggression in Autism Spectrum Disorders (ASD). Atypical antipsychotics were designed largely to replace typical antipsychotics, whose adverse effects include extrapyramidal side effects (EPS) and tardive dyskinesia (TD). However, atypical antipsychotics are associated with weight gain and disturbances in metabolic parameters, such as dyslipidemia and insulin resistance, thus increasing the risk for type II diabetes and cardiovascular disease.
Loxapine, a medium potency antipsychotic, has properties of both typical and atypical antipsychotics; it appears to have a reduced risk for both EPS and weight gain in low doses of 5-15 mg/day. Therefore, it may be a valid option to enable tapering of an atypical antipsychotic for patients with metabolic risk factors.
Objective: To investigate the ability of loxapine to help safely taper atypical antipsychotics in patients with ASD experiencing medication-induced adverse metabolic disturbances.
Table 1. Characteristics of subjects
Mean loxapine treatment duration at the time of chart review was 17 months (range 6-26 months). Final loxapine dose for 12 subjects was 5 mg/day and 5 mg bid for 3 subjects.
The safety of loxapine add-on is suggested by the following findings:
14 of 15 subjects tolerated the taper of their initial antipsychotic. Only 1 subject required the addition of another atypical to their regimen.
Behavioral outcomes, measured by CGI-I, were positive: 14 of 15 subjects had a CGI-I of 2 or 1 at ≥ 50% of their visits during the loxapine trial.
Most patients did not experience any adverse events due to loxapine. 13 of 15 subjects received a 0/7 on the AIMS, recorded at the time of chart review.
Changes in metabolic parameters did not correlate with duration of loxapine treatment. The effectiveness of loxapine add-on in reducing metabolic disturbances is suggested by the following findings:
Average change in weight was significant at -5.7 kg (SD 7.8; median -3.2 kg; p-value = 0.007).
Average change in BMI was significant at -1.9 (SD 2.4; median -1.5; p-value = 0.004).
Average decrease in triglycerides was significant at mg/dl (SD 57.3; median -26 mg/dl; p-value= 0.03).
Limitations to the study include its retrospective design and small sample size. In addition, all 15 subjects were on concomitant medications in addition to the antipsychotics, so we cannot attribute our findings solely to the action of loxapine. Still, our promising findings warrant further study of loxapine in a controlled trial.
The multisite Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study in adults with schizophrenia has contributed to the thought that typical antipsychotics remain effective, low-cost options for treatment. Because of its lower cost, suspected efficacy, and low adverse event profile, loxapine could help reduce health care costs while maintaining control of ASD symptoms for patients undergoing taper of an atypical antipsychotic.
Methods
Approval for a chart review was obtained by the OSU Institutional Review Board.
Inclusion criteria:
1. DSM-V diagnosis of ASD
2. Treatment with atypical antipsychotic or chlorpromazine
3. Presence of one or more of the following prior to loxapine trial and associated with presenting antipsychotic: history of significant weight gain associated with antipsychotic treatment, dyslipidemia, metabolic syndrome, or type II diabetes
4. Trial of adding loxapine to treat irritability and to reverse metabolic effects.
Exclusion criteria:
1. Poor medication compliance or multiple rescheduling of appointments causing treatment delays
2. Poor caregiving support, as determined by patient’s psychiatrist
Out of 25 subjects meeting the inclusion criteria, 15 subjects did not meet the exclusion criteria and so were chosen for the review after written consent was obtained. Data was extracted from patient charts. Results from standardized scales were recorded, namely the Clinical Global Impressions-Improvement (CGI-I) and the Abnormal Involuntary Movement Scale (AIMS).
Figure 1. Changes in Weight and BMI by Duration of Loxapine Treatment
Figure 2. Change in Triglycerides by Duration of Loxapine Treatment
Acknowledgements
This research was funded by the Roessler Medical Student Research Scholarship.