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Behavioral Effects of Clomipramine on Prepubertal Boys With Autistic Disorder and Severe Mental Retardation

Published online by Cambridge University Press:  07 November 2014


In an open nonblind clinical trial, clomipramine was administered to five previously medicated prepubertal boys with autistic disorder and severe mental retardation unmanageable due to behavior and motor problems. Although all five boys initially displayed marked behavioral symptom reduction, they developed behavioral newotoxicity necessitating discontinuation of clomipramine for all five and immediate hospitalization for three. Serious adverse effects included increased seizure frequency and symptoms of a serotonin syndrome. Our findings indicate that clomipramine enhances adaptive behavior and produces serious adverse effects in severely retarded autistic children whose symptoms were complicated by dyskinesias.

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1.Campbell, M, Overall, JE. Diagnostic criteria and behavior patterns in infantile autism. Psychopharmacol Bull. 1989;25:194197.Google ScholarPubMed
2.Rutter, M. The treatment of autistic children. J Child Psychol Psychiatry. 1985;26:193214.CrossRefGoogle ScholarPubMed
3.Anderson, LT, Campbell, M, Grega, DM, Perry, R, Small, AM, Green, WH. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry. 1984;141:11951202.Google ScholarPubMed
4.Anderson, LT, Campbell, M, Adams, P, Small, AM, Perry, R, Shell, J. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord. 1989;19:227239.CrossRefGoogle ScholarPubMed
5.Campbell, M. Stereotypies and tardive dyskinesia: abnormal movements in autistic children. Psychopharmacol Bull. 1990;26:260266.Google ScholarPubMed
6.Campbell, M, Adams, P, Perry, R, Spencer, EK, Overall, JE. Tardive and withdrawal dyskinesia in autistic children: a prospective study. Psychopharmacol Bull. 1988;24:251255.Google ScholarPubMed
7.Hyttel, J. Serotonin uptake inhibitors. In: Paoletti, R, Vanhoute, PM, Brunello, N, Maggi, FM, eds. Serotonin: From Cell Biology to Pharmacology and Therapeutics. Norwell, Massachusetts: Kluwer Academic Publishers; 1990:459464.CrossRefGoogle Scholar
8.Brasić, JR, Barnett, JY, Sheitman, BB, Tsaltas, MO. Adverse effects of clomipramine [letter]. J Am Acad Child Adolesc Psychiatry. 1997;36:11651166.CrossRefGoogle Scholar
9.Wilens, TE, Steingard, R, Biederman, J. Clomipramine for comorbid conditions [letter]. J Am Acad Child Adolesc Psychiatry. 1992;31:171.CrossRefGoogle Scholar
10.Austin, LS, Lydiard, RB, Ballenger, JC, et al.Dopamine blocking activity of clomipramine in patients with obsessive-compulsive disorder. Biol Psychiatry. 1991;30:225232.CrossRefGoogle ScholarPubMed
11.Cohen, DJ, Caparulo, BK, Shaywitz, BA, Bowers, MB. Dopamine and serotonin metabolism in neuropsychiatrically disturbed children. Arch Gen Psychiatry. 1977;34:545550.CrossRefGoogle ScholarPubMed
12.Young, JG, Kavanagh, ME, Anderson, GM, Shaywitz, BA, Cohen, DJ. Clinical neurochemistry of autism and associated disorders. J Autism Dev Disord. 1982;12:147165.CrossRefGoogle Scholar
13.Schain, RJ, Freedman, DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatrics. 1961;58:315320.CrossRefGoogle ScholarPubMed
14.Ritvo, ER, Yuwiler, A, Geller, E, Ornitz, E, Saeger, K, Plotkin, S. Increased blood serotonin and platelets in early infantile autism. AMA Archives of General Psychiatry. 1970;23:566572.CrossRefGoogle ScholarPubMed
15.Campbell, M, Friedman, E, DeVito, E, Greenspan, L, Collins, PJ. Blood serotonin in psychotic and braindamaged children. Journal of Autism and Childhood Schizophrenia. 1974;4:3341.CrossRefGoogle Scholar
16.Anderson, GM, Freedman, DX, Cohen, DJ, et al.Whole blood serotonin in autistic and normal subjects. J Child Psychol Psychiatry. 1987;28:885900.CrossRefGoogle ScholarPubMed
17.Yuwiler, A, Freedman, DX. Neurotransmitter research in autism. In: Schopler, E, Mesibov, GB, eds. Neurobiological Issues in Autism. New York, New York: Plenum; 1987:263284.CrossRefGoogle Scholar
18.Cook, EH. Autism: review of neurochemical investigation. Synapse. 1990;6:292308.CrossRefGoogle ScholarPubMed
19.Fuller, RW, Wong, DT. Serotonin uptake and serotonin uptake inhibition. Ann NY Acad Sci. 1990;600:6878.CrossRefGoogle Scholar
20.Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1991;48:730738.CrossRefGoogle ScholarPubMed
21.Insel, TR, Murphy, GL, Cohen, RM, Alterman, I, Kilts, D, Linnoila, M. Obsessive-compulsive disorder: a double-blind trial of clomipramine and clorgyline. Arch Gen Psychiatry. 1983;40:605612.CrossRefGoogle ScholarPubMed
22.Katz, RJ, DeVeaugh-Geiss, J, Landau, P. Clomipramine in obsessive-compulsive disorder. Biol Psychiatry. 1990;28:401414.CrossRefGoogle Scholar
23.Mavissakalian, M, Jones, B, Olson, S, Perel, JM. The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder. Psychopharmacol Bull. 1990;26:119122.Google ScholarPubMed
24.DeVeaugh-Geiss, J, Moroz, G, Biederman, J, et al.Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder—a multicenter trial. J Am Acad Child Adolesc Psychiatry. 1992;31:4549.CrossRefGoogle ScholarPubMed
25.Fallon, BA, Campeas, R, Schneier, FR, et al.Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1992;4:7075.Google ScholarPubMed
26.Insel, TR. Neurobiology of obsessive-compulsive disorder: a review. Int Clin Psychopharmacol. 1992;7 (suppl 1):3133.CrossRefGoogle ScholarPubMed
27.Ratzoni, G, Hermesh, H, Brandt, N, Lauffer, M, Munitz, H. Clomipramine efficacy for tics, obsessions, and compulsions in Tourette's syndrome and obsessive-compulsive disorder: a case study. Biol Psychiatry. 1990;27:9598.CrossRefGoogle ScholarPubMed
28.Brasic, JR, Barnett, JY, Kaplan, D, et al.Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation. Neurology. 1994;44:13091312.CrossRefGoogle ScholarPubMed
29.Wong, CM, Hollander, E. New dimensions in the OCD spectrum: autism, pathologic gambling, and compulsive buying. Primary Psychiatry. 1996;3:2034.Google Scholar
30.Hollander, E, Wong, C. Developments in the treatment of obsessive-compulsive disorder. Primary Psychiatry. 1995;2:2833.Google Scholar
31.Fraser, AD, Bryan, W, Isner, AF. Evaluation of the EMIT amitriptyline and nortriptyline assays for the determination of serum clomipramine and desmethylelomipramine. Ther Drug Monit. 1989;11:349353.CrossRefGoogle Scholar
32.Vazquez Rodriguez, AM, Arranz Peña, MA, Lopez Ibor, JJ, et al.Clomipramine test: serum level determination in three groups of psychiatric patients. J Pharm Biomed Anal. 1991;9:949952.CrossRefGoogle Scholar
33.Cook, EH, Rowlett, R, Jaselskis, C, Leventhal, BL. Fluoxetine treatment of children and adults with autistic disorder and mental retardation. J Am Acad Child Adolesc Psychiatry. 1992;31:739745.CrossRefGoogle ScholarPubMed
34.Campbell, M, Cueva, JE. Psychopharmacology in child and adolescent psychiatry: a review of the past seven years. Part I. J Am Acad Child Adolesc Psychiatry. 1995;34:11241132.CrossRefGoogle ScholarPubMed
35.Gordon, CT, Rapoport, JL, Hamburger, SD, State, RC, Mannheim, GB. Differential response of seven subjects with autistic disorder to clomipramine and desipramine. Am J Psychiatry. 1992;149:363366.Google Scholar
36.McDougle, CJ, Price, LH, Volkmar, FR, Goodman, WK, Ward-O'Brien, D, Nielsen, J, Bregman, J, Cohen, DJ. Clomipramine in autism: preliminary evidence of efficacy. J Am Acad Child Adolesc Psychiatry. 1992;31:746750.CrossRefGoogle Scholar
37.Garber, HJ, McGonigle, JJ, Slomka, GT, Monteverde, E. Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities. J Am Acad Child Adolesc Psychiatry. 1992;31:11571160.CrossRefGoogle Scholar
38.Barlas, S. NIMH researchers find clomipramine helps autism. Psychiatric Times. 1993;10(8):10.Google Scholar
39.Gordon, CT, State, RC, Nelson, JE, Hamburger, SD, Rapoport, JL. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry. 1993;50:441447.CrossRefGoogle Scholar
40.Markowitz, PI. Effect of fluoxetine on self-injurious behavior in the developmentally disabled: a preliminary study. J Clin Psychopharmacol. 1992;12:2731.CrossRefGoogle Scholar
41.Hollander, E, Wong, CM. Introduction. Obsessive-compulsive spectrum disorders. J Clin Psychiatry. 1995;56(suppl 4):36.Google Scholar
42.Brasić, JR, Barnett, JY, Aisemberg, P, et al.Dyskinesias subside off all medication in a boy with autistic disorder and severe mental retardation. Psychol Rep. 1997;81:755767.CrossRefGoogle Scholar
43.Rosenquist, PB, Bodfish, JW. Neuropsychiatric movement disorders in those with mental retardation or developmental disability. Psychiatric Annals. 1997;27:213218.CrossRefGoogle Scholar
44.Balant-Gorgia, AE, Balant, LP, Garrone, G. High blood concentrations of imipramine or clomipramine and therapeutic failure: a case report study using drug monitoring data. Ther Drug Monk. 1989;11:415420.CrossRefGoogle ScholarPubMed
45.Gouezo, F, Rop, PP, Viala, A. Influence du sexe et du tabagisme sur les concentrations plasmatiques de la clomipramine, de Pamitriptyline et de leurs metabolites déméthylés [Influence of sex and tobacco use on the plasma concentrations of clomipramine, amitriptyline, and their desmethylated metabolites]. Journal de Toxicologie Clinique et Expérimentale. 1988;8:3946.Google Scholar
46.Meiselas, KD, Spencer, EK, Oberfield, R, Peselow, ED, Angrist, B, Campbell, M. Differentiation of stereotypies from neuroleptic-related dyskinesias in autistic children. J Clin Psychopharmacol. 1989;9:207209.CrossRefGoogle ScholarPubMed
47.Schwartz, SS, Galagher, RJ, Berkson, G. Normal repetitive and abnormal stereotyped behavior of nonretarded infants and young mentally retarded children. American Journal of Mental Deficiency. 1986;90:625630.Google ScholarPubMed
48.Wehmeyer, ML. Typical and atypical repetitive motor behaviors in young children at risk for severe mental retardation. Am J Ment Retard. 1991;96:5362.Google ScholarPubMed
49.Brasić, JR, Barnett, JY, Sheitman, BB, Lafargue, RT, Ahn, SC. Clinical assessment of adventitious movements. Psychol Rep. 1998;83:723734.CrossRefGoogle ScholarPubMed
50.Kim, SW, Dysken, MW. Test of dopamine-blocking potential of clomipramine [letter]. Am J Psychiatry. 1991;148:690.Google Scholar
51.Benkelfat, C, Murphy, DL, Zohar, J, Hill, JL, Grover, G, Insel, TR. Clomipramine in obsessive-compulsive disorder: further evidence for a serotonergic mechanism of action. Arch Gen Psychiatry. 1989;46:2328.CrossRefGoogle Scholar
52.Sanchez, LE, Campbell, M, Small, AS, Cueva, JE, Armenteros, JL, Adams, PB. A pilot study of clomipramine in young autistic children. J Am Acad Child Adolesc Psychiatry. 1996;35:537544.CrossRefGoogle Scholar
53.Riddle, MA, Geller, B, Ryan, N. Another sudden death in a child treated with desipramine. J Am Acad Child Adolesc Psychiatry. 1993;32:792797.CrossRefGoogle Scholar
54.Bartels, MG, Varley, CK, Mitchell, J, Stamm, SJ. Pediatric cardiovascular effects of imipramine and desipramine. J Am Acad Child Adolesc Psychiatry. 1991;30:100103.CrossRefGoogle ScholarPubMed
55.Biederman, J, Baldessarini, RJ, Goldblatt, A, Lapey, KA, Doyle, A, Hesslein, PS. A naturalistic study of 24-hour electrocardiographic recordings and echocardiographic findings in children and adolescents treated with desipramine. J Am Acad Child Adolesc Psychiatry. 1993;32:805813.CrossRefGoogle ScholarPubMed
56.Fetner, HH, Geller, B. Lithium and tricyclic antidepressants. Psychiatr Clin North Am. 1992;15:223241.Google ScholarPubMed
57.Wilens, TE, Biederman, J, Baldessarini, RJ, Puopolo, PR, Flood, JG. Electrocardiographic effects of desipramine and 2-hydroxydesipramine in children, adolescents, and adults treated with desipramine. J Am Acad Child Adolesc Psychiatry. 1993;32:798804.CrossRefGoogle ScholarPubMed
58.Preskorn, SH, Jerkovich, GS. Central nervous system toxicity of tricyclic antidepressants: phenomenology, course, risk factors, and role of therapeutic drug monitoring. J Clin Psychopharmacol. 1990;10:8895.CrossRefGoogle ScholarPubMed
59.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., rev. Washington, DC: American Psychiatric Association; 1987. 2839.Google ScholarPubMed
60.Munetz, MR, Benjamin, S. How to examine patients using the abnormal Involuntary Movement Scale. Hospital and Community Psychiatry. 1988;39:11721177.Google ScholarPubMed
61.Sanchez, LE, Adams, PB, Uysal, S, Hallin, A, Campbell, M, Small, AM. A comparison of live and videotaped ratings: clomipramine and haloperidol in autism. Psychopharmacol Bull. 1995;31:371378.Google ScholarPubMed
62.Guy, W. Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology, Revised, 1976. (DHEW Publication No. (ADM) 76-338.) Rockville, Maryland: United Stated Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration; 1976:217222.Google Scholar
63.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1980:4145.Google ScholarPubMed
64.Leckman, JF, Towbin, KE, Ort, SI, Cohen, DJ. Clinical assessment of tic disorder severity. In: Cohen, DJ, Bruun, RD, Leckman, JF, eds. Tourette's Syndrome & Tic Disorders. New York, New York: John Wiley & Sons; 1988:5578.Google ScholarPubMed
65.Fish, B. Children's Psychiatric Rating Scale. Psychopharmacol Bull. 1985;21:753770.Google Scholar
66.Kay, SR, Wolkenfeld, F, Murrill, LM. Profiles of aggression among psychiatric patients: I. Nature and prevalence. J Nerv Ment Dis. 1988;176:539546.CrossRefGoogle ScholarPubMed
67.Shaffer, D, Gould, MS, Brasic, J, Ambrosini, P, Fisher, P, Bird, H, Aluwahlia, S. A Children's Global Assessment Scale (CGAS) (for children 4 to 16 years of age). Psychopharmacol Bull. 1985;21:747748.Google Scholar
68.Adler, LA, Duncan, E, Kim, A, Hemdal, P, Rotrosen, J, Angrist, B. Akathisia: selective β- blockers and rating instruments. Psychopharmacol Bull. 1989;25:451456.Google ScholarPubMed
69.Lipinski, JF, Keck, PE, McElroy, SL. β-adrenergic antagonists in psychosis: is improvement due to treatment of neuroleptic-induced akathisia? J Clin Psychopharmacol. 1988;8:409416.Google ScholarPubMed
70.Conover, WJ. The one-sample or matched pairs case. Practical Nonparametric Statistics. 2nd ed. New York, New York: John Wiley & Sons; 1980:278294.Google Scholar
71.Brasić, JR, Barnett, JY, Ahn, SC, Nadrich, RH, Will, MV, Clair, A. Clinical assessment of self-injurious behavior. Psychol Rep. 1997;80;155160.CrossRefGoogle ScholarPubMed
72.Brasić, JR, Barnett, JY, Sheitman, BB, et al.Clomipramine enhances adaptive behavior in autistic boys [abstract]. 9th World Congress of Psychiatry Abstracts, Rio de Janeiro, Brazil, June 6-12, 1993. 1993:76, Abstract 298.Google Scholar
73.Brasić, JR, Barnett, JY. Hyperkinesias in a prepubertal boy with autistic disorder treated with haloperidol and valproic acid. Psychol Rep. 1997;80:163170.CrossRefGoogle Scholar
74.Mikkelsen, EJ, Albert, LG, Emens, M, Rubin, E. The efficacy of antidepressant medication for individuals with mental retardation. Psychiatric Annals. 1997;27:198206.CrossRefGoogle Scholar
75.Botstein, P. Is QT interval prolongation harmful? A regulatory perspective. Am J Cardiol. 1993;72(6):50B52B.CrossRefGoogle ScholarPubMed
76.Lipicky, RJ. A viewpoint on drugs that prolong the QTc interval. Am J Cardiol. 1993;72(6):53B54B.CrossRefGoogle ScholarPubMed
77.Tingelstad, JB. The cardiotoxicity of the tricyclics. J Am Acad Child Adolesc Psychiatry. 1991;30:845846.Google ScholarPubMed
78.Riddle, MA, Nelson, JC, Kleinman, CS, et al.Sudden death in children receiving Norpramin: a review of three reported cases and commentary. J Am Acad Child Adolesc Psychiatry. 1991;30:104108.CrossRefGoogle ScholarPubMed
79.Geller, B. Commentary on unexplained deaths of children on Norpramin. J Am Acad Child Adolesc Psychiatry. 1991;30:682683.CrossRefGoogle ScholarPubMed
80.Kasvikis, Y, Marks, I. Clomipramine in obsessive-compulsive ritualisers treated with exposure therapy: relations between dose, plasma level, outcome and side effects. Psychopharmacology. 1988;95:113118.CrossRefGoogle Scholar
81.Kutcher, SP. Child and Adolescent Psychopharmacology. Philadelphia, Pennsylvania; W. B. Saunders Company; 1997.Google ScholarPubMed
82.Whelan, AJ. Patient care in internal medicine. In: Ewald, GA, McKenzie, CR, eds. Manual of Medical Therapeutics. 28th ed. Boston, Mass: Little, Brown and Company; 1995:128.Google Scholar
83.Sternbach, H. The serotonin syndrome. Am J Psychiatry. 1991;148:705713.Google ScholarPubMed
84.Sussman, N. The potential benefits of serotonin receptor-specific agents. J Clin Psychiatry. 1994;55(2 part 3, suppl):4551.Google ScholarPubMed
85.Geller, DA, Biederman, J, Reed, ED, Spencer, T, Wilens, TE. Similarities in response to fluoxetine in the treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1995;34:3644.CrossRefGoogle ScholarPubMed
86.Leo, RJ. Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry. 1996;57:449454.CrossRefGoogle ScholarPubMed
87.Wilde, MI, Plosker, GL, Benfield, P. Fluvoxamine: an updated review of its pharmacology, and therapeutic use in depressive illness. Drugs. 1993;46:895924.CrossRefGoogle ScholarPubMed
88.Brasić, JR, Young, JG. Research design, measures, and statistics. In: Robson, KS, ed. Manual of Clinical Child and Adolescent Psychiatry. Rev. ed. Washington, DC: American Psychiatric Press, Inc.; 1994:435463.Google Scholar
89.Richelson, E. Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs. Mayo Clin Proc. 1997;72;835847.CrossRefGoogle Scholar
90.Altamura, AC. The clinical use of anticholinergic drugs in neuroleptic induced extrapyramidal side-effects. A controversial issue. In: Nappi, G, Hornykiewicz, O, Fariello, RG, Agnoli, A, Klawans, H, eds. Neurodegenerative Disorders: The Role Played by Endotoxins and Xenobiotics. New York, NY: Raven Press; 1988:179192.Google Scholar
91.Campbell, M, Adams, PB, Small, AM, et al.Lithium in hospitalized aggressive children with conduct disorder: a double-blind and placebo-controlled study. J Am Acad Child Adolesc Psychiatry. 1995;34:445453.CrossRefGoogle ScholarPubMed
92.Briley, M, Moret, C. 5-HT and antidepressants: in vitro and in vivo release studies [letter]. Trends Pharmacol Sci. 1993;14:396397.CrossRefGoogle Scholar
93.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:8385.Google ScholarPubMed

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