olanzapine and Chromosome-Deletion

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 22; Drug Therapy, Combination; Humans; Intellectual Disability; Lithium Compounds; Male; Mutation; Nerve Tissue Proteins; Olanzapine

Olanzapine is widely used for the treatment of schizophrenia and is considered a first line medication in India. Along with other factors, the variation in response and side effects to this agent may be accounted for by genetic differences among patients. Olanzapine was administered for 6 weeks to Indian subjects with schizophrenia or schizoaffective disorder (DSM-IV, n=130), as part of an open label study. Intent-to-treat analysis was performed, and 10 polymorphic markers from seven genes (dopamine D1, D2, D3 and D4 receptors, serotonin 2A receptor and the drug-metabolizing enzymes (CYP1A2 and CYP2D6)), together with demographic and clinical variables, were analyzed as potential predictors of response. Olanzapine was efficacious, but significant weight gain was noted. Baseline weight and a 120 bp deletion polymorphism at the dopamine receptor D4 (DRD4) gene were associated with changes in symptom scores. Predictable covariates of treatment response were also noted. These results merit replicate studies.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Chromosome Deletion; Developing Countries; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; India; Male; Middle Aged; Olanzapine; Polymorphism, Genetic; Psychiatric Status Rating Scales; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult