Table S1: Key Search Terms used in Literature Search Fluoxetine
Autism spectrum disorder Efficacy
Autism
Asperger’s disease
Pervasive developmental disorder Selective serotonin reuptake inhibitor SSRI
Safety
Improvement Response Responders
Aberrant Behavior Checklist (ABC)
Autism Treatment Evaluation Checklist (ATEC) Childhood Autism Rating Scale (CARS)
Clinical Global Impression (CGI)
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Comorbidity
Hyperactivity Agitation Restlessness
Bibliography of Included Studies
1. Buchsbaum MS, Hollander E, Haznedar MM, et al. Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study. Int J Neuropsychopharmacol. 2001;4(2):119–25.
2. Cook EH Jr, Rowlett R, Jaselskis C, et al. Fluoxetine treatment of children and adults with autistic disorder and mental retardation. J Am Acad Child Adolesc Psychiatry. 1992;31(4):739–45.
3. DeLong GR, Teague LA, McSwain Kamran M. Effects of fluoxetine treatment in young children with idiopathic autism. Dev Med Child Neurol. 1998;40(8):551–62.
4. DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev Med Child Neurol. 2002;44(10):652–9.
5. Desousa A. An open-label trial of risperidone and fluoxetine in children with autistic disorder. Indian J Psychol Med. 2010;32(1):17–21.
6. Fatemi SH, Realmuto GM, Khan L, et al. Fluoxetine in treatment of adolescent patients with autism: a longitudinal open trial. J Autism Dev Disord. 1998;28(4):303–7.
7. Ghaziuddin M, Tsai L, Ghaziuddin N. Fluoxetine in autism with depression. J Am Acad Child Adolesc Psychiatry. 1991;30(3):508–9.
8. Hollander E, Phillips A, Chaplin W, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology. 2005;30(3):582–9.
9. Hollander E, Soorya L, Chaplin W, et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am J Psychiatry. 2012;169(3):292–9.
10. Koshes RJ. Use of fluoxetine for obsessive-compulsive behavior in adults with autism. Am J Psychiatry. 1997;154:578–79.
11. Makkonen I. Childhood autism, aspects of growth factors and monoaminergic transporters in etiopathogenesis. University of Eastern Finland, Faculty of Health Sciences. Publications of the University of Eastern Finland. Dissertations in Health Sciences 101, 2012.
12. Peral M, Alcamí M, Gilaberte I. Fluoxetine in children with autism. J Am Acad Child Adolesc Psychiatry. 1999;38(12):1472–3.
13. Todd RD. Fluoxetine in autism. Am J Psychiatry. 1991;148:1089–90.
Table S2: Important characteristics of the included studies
Study identity Country Condition Diagnosis n Design Treatmen
t (months)
Age ± SD (years)
% males
Tool
Buchsbaum 2001
USA Autism, Asperger's syndrome
DSM-IV 6 Single
blind-RCT
4 30.5±8.6 CGI, Y-
BOCS
Cook 1992 USA Autistic disorder DSM-III-R 23 Open label 6 15.9±6.2 78 CGI,
CGI-OCD DeLong 1998 USA Idiopathic autistic
disorder
DSM-IV 37 Open label 2.64±1.21 72
DeLong 2002 USA Idiopathic autistic disorder
Childhood Autism Ratings Scale, Autism Diagnostic Observation Schedule
129 Open label 32 4.6±2.5
Desousa 2010 India Autistic disorder DSM-IV, Autism Diagnostic Interview – Revised
20 Open label 4 ABC,
CGI
Fatemi 1998 USA Autistic disorder DSM-IV 7 Open label 18 16±3.9 57 ABC
Ghaziuddin 1991 USA Autistic disorder 4 Case reports 18±2.2 67
Hollander 2005 USA ASD Autism Diagnostic Interview, Autism
Diagnostic Observation Schedule, DSM-IV TR
19 Double blind-RCT
1 9.1±3.7 68 CGI, Y-
BOCS
Hollander 2012 USA ASD DSM-IV 22 Double
blind-RCT
3 31.8±14.2
6
64 CGI, Y-
BOCS
Koshes 1997 2 Open label 2.5 34±11 50
Makkonen 2012 Finland Autistic disorder 25 Open label 6 ATEC
Pearl 1999 Spain Autistic disorder Clinical Global Impression 5 Open label 6 CGI
Todd 1991 4 Open label 16 12.8±4.65 50
Abbreviations: Aberrant Behavior Checklist (ABC); ASD, autism spectrum disorder; Autism Treatment Evaluation Checklist (ATEC), Childhood Autism Rating Scale (CARS);
Clinical Global Impression (CGI), DSM-IV TR, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, text revision; RCT, randomized controlled trial; Yale- Brown Obsessive-Compulsive Scale (Y-BOCS),
Figure S1: A flowchart of study screening process showing the retrieval, exclusions and inclusion of the studies.
Full-text articles excluded, with reasons*
(n = 23)
Combinational use of fluoxetine
Used other related drugs e.g. Paroxetine,
Atomoxetine
Used fluoxetine for evaluating brain changes
MRI-based structural studies evaluating fluoxetine effects
Recruited non-ASD but related disorder patients
Records excluded (n = 1021) Records after duplicates removed
(n = 1057)
In cl u d e d El ig ib ili ty Sc re e n in g Id e n t f ca t o n
Studies included in quantitative synthesis
(n = 13) Studies included in qualitative synthesis
(n = 13)
Full-text articles assessed for eligibility
(n = 36) Records screened
(n = 1057) Records identified through
database searching (n = 1324)
Additional records identified through other sources
(n = 43)
Figure S2: A funnel plot showing the existence of publication bias and a possible number of missing studies (circles within brackets). Theta = Percent response rate of fluoxetine treatment.
Figure S3: A forest graph showing the outcome of the pooling of individual effect size of the percent incidence of hyperactivity / restlessness / agitation reported in the included studies.
Table S3: Other reported side effects of Fluoxetine
Insomnia 22%
Drowsiness / sedation 18%
Elated affect 17%
Anxiety 16%
Vivid dreams 14%
Dry mouth 14%
Headache 14%
Decreased appetite 11%
Anorexia 10%
Urinary infection 10%
Increased screaming 9%
Nausea 9%
Depressed mood or depression 9%
Fatigue 5%
Neck pain 5%
Numbness 5%
Polyuria 5%
Salty taste 5%
Suicidal thoughts 5%
Trembling 5%
Vertigo 5%
Diarrhea 5%
Increased socially inappropriate behavior 4%
Crying spells 4%
Yawning 4%
Maculopapular rash 4%
