Low Dose Loxapine: Neuromotor Side Effects and Tolerability in Autism Spectrum Disorders.
OBJECTIVE
New and repurposed drugs are urgently needed to treat individuals with autism spectrum disorders (ASD). Loxapine (LOX) in low doses of 5-15 mg/day resembles an atypical antipsychotic (Stahl 2002 ). Our recent open pilot study of LOX found significant behavioral improvements and overall weight neutrality in 16 adolescents and adults with ASD. The present study examined an outpatient sample for LOX neuromotor tolerability.


METHODS
Consecutive outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) ASD diagnoses receiving LOX were examined for tardive dyskinesia (TD) and extrapyramidal side effects (EPS) using the Dyskinesia Identification System: Condensed User Scale (DISCUS), and for akathisia using the Barnes Akathisia Rating Scale. Data were also then retrospectively extracted from clinic charts regarding age, gender, diagnoses, LOX doses, treatment duration, concomitant medications, and LOX dosage reductions.


RESULTS
Thirty-four subjects (25 male, 9 female) participated. Mean age was 23.4 years at LOX initiation (range 8-52). Thirteen subjects (38.2%) received loxapine for ≥5 years. Mean LOX dose was 8.9 mg/day (range 5-30 mg) and mean duration was 4.2 years (range 0.8-13). Fourteen subjects (41.2%) received concomitant atypical antipsychotics. Benztropine was prescribed in 5 of 34 subjects (14.7%). Three subjects manifested tics at baseline, but lower final DISCUS scores. Subject 26, with Prader-Willi syndrome, manifested TD. Apart from LOX 5 mg daily he received paroxetine 40 mg daily, which reduces LOX metabolism significantly. Akathisia objective scores were positive in 6 subjects (17.6%): Subject 2 scored 3 (pacing was present also at baseline); subjects 6, 7, and 11 each scored 1; and subjects 18 and 23 each scored 2. Six of 9 subjects (66.7%) with expressive language were positive for subjective akathisia.


CONCLUSIONS
Low dose LOX was well tolerated, with lower than expected TD rates. This confirms clinical resemblance to an atypical antipsychotic. Individuals with neuromuscular problems including Prader-Willi Syndrome receiving LOX require close monitoring. Further study of LOX in ASD is warranted.
1 Department of Psychiatry, The Ohio State University Nisonger Center , Columbus, Ohio.|2 Department of Psychiatry, University of Kansas Medical Center , Kansas City, Kansas.
Jessica A
JA
Hellings
2 Department of Psychiatry, University of Kansas Medical Center , Kansas City, Kansas.|3 Ross University School of Medicine , Miramar, Florida.
Mandar
M
Jadhav
1 Department of Psychiatry, The Ohio State University Nisonger Center , Columbus, Ohio.|4 The Ohio State University College of Medicine , Columbus, Ohio.
Seema
S
Jain
2 Department of Psychiatry, University of Kansas Medical Center , Kansas City, Kansas.
Sneha
S
Jadhav
2 Department of Psychiatry, University of Kansas Medical Center , Kansas City, Kansas.
Ann
A
Genovese
D000293:Adolescent; D000328:Adult; D017109:Akathisia, Drug-Induced / Q000150:complications / Q000453:epidemiology*; D000067877:Autism Spectrum Disorder / Q000150:complications / Q000188:drug therapy*; D002648:Child; D003430:Cross-Sectional Studies; D004409:Dyskinesia, Drug-Induced / Q000150:complications / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
D008152:Loxapine