Loxapine Substitution for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Retrospective Chart Review
Atypical antipsychotics are widely used to treat irritability and aggression in Autism Spectrum Disorders (ASD), despite side effects of significant weight gain and associated metabolic disturbances. Our findings regarding low-dose loxapine, a typical antipsychotic with atypical properties, warrant further study in reversal of metabolic illness associated with atypical antipsychotic treatment in ASD.
To examine a naturalistic outpatient clinic sample of adolescents and adults with ASD who received loxapine for weight and metabolic indicator outcomes. We hypothesized that substitution of loxapine for atypical antipsychotics or chlorpromazine would have beneficial effects on weight and metabolic indicators as well as behavioral outcomes.
We performed a retrospective chart review of consecutive adolescents and adults with DSM-IV-TR ASD presenting on an atypical antipsychotic (n=14) or chlorpromazine (n=1), together with at least one form of metabolic disturbance before low dose loxapine substitution.
Subjects were 12 males and 3 females. Mean age was 31.7 years (range 16-61 years). Mean loxapine treatment duration at the time of chart review was 11.5 months (range 3-20 months). Final loxapine dose for 12 subjects was 5 mg/day and 10 mg/day for 3 subjects. 14 of 15 subjects tolerated addition of loxapine and tapering or discontinuation of their presenting antipsychotic. At the time of chart review, 14 of 15 subjects had a Clinical Global Impressions Scale- Improvement (CGI-I) of 2 (Much Improved) or 1 (Very Much Improved). In addition, 13 of 15 subjects had a CGI-I of 2 or 1 at ≥ 50% of their visits during loxapine treatment. Mean weight loss was significant at -6.65 kg (SD 10.07; median -3.22 kg). Mean BMI reduction was significant at -2.47 (SD 3.3; median -1.67). Mild extrapyramidal symptoms were noted in 3 subjects. No significant change in blood pressure or pulse was noted. Detailed metabolic indicator data, including fasting lipids, fasting glucose, and HbA1c, will be elaborated on.
Our findings suggest that loxapine may safely enable tapering of an atypical antipsychotic in order to reverse drug-induced weight gain in patients with ASD.