Skip to main content
SpringerLink
Log in

Low-Dose Fluvoxamine Treatment of Children and Adolescents with Pervasive Developmental Disorders: A Prospective, Open-Label Study

  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

The objective of this study was to assess the efficacy and tolerability of low-dose fluvoxamine (1.5 mg/kg/day) in youngsters with pervasive developmental disorders (PDDs). This was a prospective, open-label trial that included 18 subjects with a mean age of 11.3 ± 3.6 years. Fourteen children (78%) completed the 10-week study. Premature discontinuation due to behavioral activation occurred in three participants. Although there was no response for the group as a whole, eight subjects (including all four females) were considered at least partial responders in intent-to-treat analyses. Neither pubertal status nor serotonin levels predicted clinical response. Fluvoxamine can be beneficial in the treatment of select children and adolescents with PDDs. Gender differences in selective serotonin reuptake inhibitor (SSRI) response warrant further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anderson, G. M., Feibel, F. C., & Cohen, D. J. (1987). Determination of serotonin in whole blood, platelet-rich plasma, plateletpoor plasma and plasma ultrafiltrate. Life Science, 40, 1063-1070.

    Google Scholar 

  • Arnold, L. E., Aman, M. G., Martin, A., Collier-Crespin, A., Vitiello, B., Tierney, E., Asarnow, R., Bell-Bradshaw, F., Freeman, B. J., Gates-Ulanet, P., Klin, A., McCracken, J. T., McDougle, C. J., McGough, J. J., Posey, D. J., Scahill, L., Swiezy, N. B., Ritz, L., & Volkmar, F. (2000). Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology. Journal of Autism and Developmental Disorders, 30, 99-111.

    Google Scholar 

  • Berry, C. A., Shaywitz, S., & Shaywitz, B. (1985). Girls with attention deficit disorder: A silent minority? A report on behavioral and cognitive characteristics. Pediatrics, 76, 801-809.

    Google Scholar 

  • Birmaher, B., Brent, D. A., Chiappetta, L., Bridge, J., Monga, S., & Baugher, M. (1999). Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): A replication study. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 1230-1236.

    Google Scholar 

  • Brady, K., Pearlstein, T., Asnis, G. M., Baker, D., Rothbaum, B., Sikes, C. R., & Farfel, G. M. (2000). Efficacy and safety of sertraline treatment of posttraumatic stress disorder: A randomized controlled trial. Journal of the American Medical Association, 283, 1837-1844.

    Google Scholar 

  • Chouinard, G., Goodman, W., Greist, J., Jenike, M., Rasmussen, S., White, K., Hackett, E., Gaffney, M., & Bick, P. A. (1990). Results of a double-blind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessivecompulsive disorder. Psychopharmacology Bulletin, 26, 279-284.

    Google Scholar 

  • Cook, E. H., Jr., Rowlett, R., Jaselskis, C., & Leventhal, B. L. (1992). Fluoxetine treatment of children and adults with autistic disorder and mental retardation. Journal of the American Academy of Child and Adolescent Psychiatry, 31, 739-745.

    Google Scholar 

  • Davidson, J. R., Rothbaum, B. O., van der Kolk, B. A., Sikes, C. R., & Farfel, G. M. (2001). Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Archives of General Psychiatry, 58, 485-492.

    Google Scholar 

  • Eme, R., & Kavanaugh, L. (1995). Sex differences in conduct disorder. Journal of Clinical Child Psychology, 24, 406-426.

    Google Scholar 

  • Epperson, N., Czarkowski, K. A., Ward-O'Brien, D., Weiss, E., Gueorguieva, R., Jatlow, P., & Anderson, G. M. (2001). Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. American Journal of Psychiatry, 158, 1631-1637.

    Google Scholar 

  • Freiman, J. A., Chalmers, T. C., Smith, H., Jr., & Kuebler, R. R. (1978). The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial: Survey of 71 “negative” trials. New England Journal of Medicine, 299, 690-694.

    Google Scholar 

  • Geller, D. A., Hoog, S. L., Heiligenstein, J. H., Ricardi, R. K., Tamura, R., Kluszynski, S., & Jacobson, J. G. (2001). Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. Journal of the American Academy of Child and Adolescent Psychiatry, 40, 773-739.

    Google Scholar 

  • Golomb, M., Fava, M., Abraham, M., & Rosenbaum, J. F. (1995). Gender differences in personality disorders. American Journal of Psychiatry, 152, 579-582.

    Google Scholar 

  • Gordon, C. T., Rapoport, J. L., Hamburger, S. D., State, R. C., & Mannheim, G. B. (1992). Differential response of seven subjects with autistic disorder to clomipramine and desipramine. American Journal of Psychiatry, 149, 363-366.

    Google Scholar 

  • Gordon, C. T., State, R. C., Nelson, J. E., Hamburger, S. D., & Rapoport, J. L. (1993). A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Archives of General Psychiatry, 50, 441-447.

    Google Scholar 

  • Greist, J. H., Jefferson, J. W., Kobak, K. A., Chouinard, G., DuBoff, E., Halaris, A., Kim, S. W., Koran, L., Liebowtiz, M. R., Lydiard, B., et al. (1995). A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder. International Clinics in Psychopharmacol, 10, 57-65.

    Google Scholar 

  • Guy, W. (1976). Clinical Global Impression (CGI). In ECDEU assessment manual for psychopharmacology (publication no. 76–338). Washington, DC: U.S. Department of Health, Education and Welfare.

    Google Scholar 

  • Klin, A., Volkmar, F. R., Sparrow, S. S., Cicchetti, D. V., & Rourke, B. P. (1995). Validity and neuropsychological characterization of Asperger syndrome: Convergence with nonverbal learning disabilities syndrome. Journal of Child Psychology and Psychiatry, 36, 1127-1140.

    Google Scholar 

  • Kornstein, S. G., Schatzberg, A. F., Thase, M. E., Yonkers, K. A., McCullough, J. P., Keitner, G. I., Gelenberg, A. J., Davis, S. M., Harrison, W. M., & Keller, M. B. (2000). Gender differences in treatment response to sertraline versus imipramine in chronic depression. American Journal of Psychiatry, 157, 1445-1452.

    Google Scholar 

  • Labellarte, M. J., Ginsburg, G. S., Walkup, J. T., & Riddle, M. A. (1999). The treatment of anxiety disorders in children and adolescents. Biological Psychiatry, 46, 1567-1578.

    Google Scholar 

  • Leiter, R. G. (1948). Leiter International Performance Scale. Chicago, Illinois: Stoelting.

    Google Scholar 

  • Liebowitz, M. R. (1999). Update on the diagnosis and treatment of social anxiety disorder. Journal of Clinical Psychiatry, 60 (Suppl 18), 22-26.

    Google Scholar 

  • Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., & Schopler, E. (1989). Autism diagnostic observation schedule: A standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders, 19, 185-212.

    Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659-685.

    Google Scholar 

  • March, J. S., Biederman, J., Wolkow, R., Safferman, A., Mardekian, J., Cook, E. H., Cutler, N. R., Dominguez, R., Ferguson, J., Muller, B., Riesenberg, R., Rosenthal, M., Sallee, F. R., & Wagner, K. D. (1998). Sertraline in children and adolescents with obsessive-compulsive disorder: A multicenter randomized controlled trial. Journal of the American Medical Association, 280, 1752-1756.

    Google Scholar 

  • Martensson, B., Wagner, A., Beck, O., Brodin, K., Montero, D., & Asberg, M. (1991). Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3Himipramine binding and serotonin uptake and concentration in major depressive disorder. Acta Psychiatrica Scandinavica, 83, 125-133.

    Google Scholar 

  • Martin, A., Scahill, L., Klin, A., & Volkmar, F. R. (1999). Higherfunctioning pervasive developmental disorders: rates and patterns of psychotropic drug use. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 923-931.

    Google Scholar 

  • McBride, P. A., Anderson, G. M., Hertzig, M. E., Snow, M. E., Thompson, S. M., Khait, V. D., Shapiro, T., & Cohen, D. J. (1998). Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 767-776.

    Google Scholar 

  • McDougle, C. J., Kresch, L. E., Goodman, W. K., Naylor, S. T., Volkmar, F. R., Cohen, D. J., & Price, L. H. (1995). A casecontrolled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder. American Journal of Psychiatry, 152, 772-777.

    Google Scholar 

  • McDougle, C. J., Naylor, S. T., Cohen, D. J., Volkmar, F. R., Heninger, G. R., & Price, L. H. (1996). A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Archives of General Psychiatry, 53, 1001-1008.

    Google Scholar 

  • Muck-Seler, D., Jakovljevic, M., & Deanovic, Z. (1991). Effect of antidepressant treatment on platelet 5-HT content and relation to therapeutic outcome in unipolar depressive patients. Journal of Affective Disorders, 23, 157-164.

    Google Scholar 

  • Narayan, M., Anderson, G., Cellar, J., Mallison, R. T., Price, L. H., & Nelson, J. C. (1998). Serotonin transporter-blocking properties of nefazodone assessed by measurement of platelet serotonin. Journal of Clinical Psychopharmacology, 18, 67-71.

    Google Scholar 

  • Potenza, M. N., & McDougle, C. J. (2001). Reply to comments on “Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study.” Journal of Clinical Psychopharmacology, 21, 246-247.

    Google Scholar 

  • Riddle, M. A., Reeve, E. A., Yaryura-Toblas, J. A., Yang, H. M., Claghorn, J. L., Gaffney, G., Greist, J. H., Holland, D., McConville, B. J., Pigott, T., & Walkup, J. T. (2001). Fluvoxamine for children and adolescents with obsessive-compulsive disorder: A randomized, controlled, multicenter trial. Journal of the American Academy Child and Adolescent Psychiatry, 40, 222-229.

    Google Scholar 

  • Riddle, M. A., Scahill, L., King, R. A., Hardin, M. T., Anderson, G. M., Ort, S. I., Smith, J. C., Leckman, J. F., & Cohen, D. J. (1992). Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 31, 1062-1069.

    Google Scholar 

  • RUPP. (2001). Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group. New England Journal of Medicine, 344, 1279-1285.

    Google Scholar 

  • Scahill, L., Chappell, P. B., Kim, Y. S., Schultz, R. T., Katsovich, L., Shepherd, E., Arnsten, A. F., Cohen, D. J., & Leckman, J. F. (2001). A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. American Journal of Psychiatry, 158, 1067-1074.

    Google Scholar 

  • Scahill, L., Riddle, M. A., McSwiggin-Hardin, M., Ort, S. I., King, R. A., Goodman, W. K., Cicchetti, D., & Leckman, J. F. (1997). Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 844-852.

    Google Scholar 

  • Schore, A. (1994). The origins of infantile sexuality and psychological gender. In Affect regulation and the origin of the self: The neurobiology of emotional development. (pp. 260-268). Hillsdale, NJ: Lawrence Erlbaum Associates.

    Google Scholar 

  • Shaywitz, B. A., Shaywitz, S. E., Pugh, K. R., Constable, R. T., Skudlarski, P., Fulbright, R. K., Bronen, R. A., Fletcher, J. M., Shankweiler, D. P., Katz, L. & et al. (1995). Sex differences in the functional organization of the brain for language. Nature, 373, 607-609.

    Google Scholar 

  • Smeraldi, E., Zanardi, R., Benedetti, F., Di Bella, D., Perez, J., & Catalano, M. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Molecular Psychiatry, 3, 508-511.

    Google Scholar 

  • Steingard, R. J., Zimnitzky, B., DeMaso, D. R., Bauman, M. L., & Bucci, J. P. (1997). Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. Journal of Child and Adolescent Psychopharmacology, 7, 9-15.

    Google Scholar 

  • Wechsler, D. (1992). Manual for the Wechsler Intelligence Scale for Children (3rd edition). San Antonio, Texas: The Psychological Corporation.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Child Study Center, Yale University, New Haven, Connecticut

    Andrés Martin, Kathleen Koenig, George M. Anderson & Lawrence Scahill

  2. Children's Psychiatric Inpatient Service, Yale-New Haven Hospital, New Haven, Connecticut

    Andrés Martin

  3. Child Study Center, Yale University School of Medicine, 230 South Frontage Road, P.O. Box 207900, New Haven, CT, 06520-7900

    Andrés Martin

  4. Department of Laboratory Medicine, School of Medicine, Yale University, New Haven, Connecticut

    George M. Anderson

  5. School of Nursing, Yale University, New Haven, Connecticut

    Lawrence Scahill

Authors
  1. Andrés Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen Koenig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George M. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lawrence Scahill
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, A., Koenig, K., Anderson, G.M. et al. Low-Dose Fluvoxamine Treatment of Children and Adolescents with Pervasive Developmental Disorders: A Prospective, Open-Label Study. J Autism Dev Disord 33, 77–85 (2003). https://doi.org/10.1023/A:1022234605695

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022234605695

Search

Navigation