title: Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder.
abstract: OBJECTIVE
  To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group.
  
  
  METHODS
  In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales.
  
  
  RESULTS
  Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p b 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser–Meyer–Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam.
  
  
  CONCLUSIONS
  Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD.
authors.affiliation: Seoul National University Bundang Hospital (SNUBH), Seoul, Republic of Korea. Electronic address: giuliana.gallicarminati@gmail.com.
authors.forename: Giuliana Galli
authors.initials: GG
authors.lastname: Carminati
authors.affiliation: Hôpitaux Universitaire de Genève, Département de Santé Mentale et Psychiatrie, Service des Spécialités Psychiatriques, Unité du Développement Mental, Belle-Idée, bat. Jura, chemin Petit Bel-Air 2, 1225 Chêne-Bourg, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gerber
authors.affiliation: Hôpitaux Universitaire de Genève, Département de Santé Mentale et Psychiatrie, Service des Spécialités Psychiatriques, Unité du Développement Mental, Belle-Idée, bat. Jura, chemin Petit Bel-Air 2, 1225 Chêne-Bourg, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Darbellay
authors.affiliation: Hôpitaux Universitaire de Genève, Département de Santé Mentale et Psychiatrie, Service des Spécialités Psychiatriques, Unité du Développement Mental, Belle-Idée, bat. Jura, chemin Petit Bel-Air 2, 1225 Chêne-Bourg, Switzerland.
authors.forename: Markus Mathaus
authors.initials: MM
authors.lastname: Kosel
authors.affiliation: Service de Pédiatrie, Clinique des Grangettes, Chemin des Grangettes 7, 1224 Chêne-Bougeries, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deriaz
authors.affiliation: Hôpitaux Universitaire de Genève, Centre de Recherche Clinique, Unité d'investigation clinique, 4-AL, Hôpital Cantonal, rue Micheli-du-Crest 24, 1211 Genève 14, Switzerland.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Chabert
authors.affiliation: Département de Pathologie Clinique, Laboratoire Centrale de Chimie Clinique Hôpitaux Universitaire de Genève, Service médecine de laboratoire, Hôpital Cantonal, rue Micheli-du-Crest 24, 1211 Genève 14, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Fathi
authors.affiliation: Service de Psychiatrie II, Pôle de Psychiatrie et Santé Mentale, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, BP 426, F-67091 Strasbourg Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bertschy
authors.affiliation: Université de Genève, Rue Michel Servet 1, 1205 Genève, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Ferrero
authors.affiliation: Physicist at CERN, 1211 Genève 23, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Carminati
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D002998:Clonazepam / Q000008:administration & dosage*; D003006:Clopenthixol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D011619:Psychotropic Drugs; D002998:Clonazepam; D000069470:Venlafaxine Hydrochloride; D003006:Clopenthixol
keywords: Aggressiveness; Autism spectrum disorder; Behavioral disorder; Venlafaxine