The authors used meta-analysis to determine the effect size for nonstimulant medications on symptoms of overt aggression-related behaviors in referred children and adolescents with serious emotional and behavioral disturbances.A review of the literature between 1970 and 2001 revealed 33 studies meeting exclusion/inclusion criteria and yielding 37 independent effects for neuroleptic, atypical antipsychotic, mood stabilizer, antidepressant, and adrenergic agents on symptoms of overt aggression.To acquire statistical power, two groups of medications were created and analyzed.The first group consisted of medications for more severely ill children and included neuroleptics, atypical antipsychotics, and mood stabilizers.The second group consisted of medications for less severely ill children and included antidepressants and adrenergic agents. Overall weighted mean effect sizes were moderate to large for overt aggression within a heterogeneous group of psychiatric disorders. Moderators of effect size included drug group, study design, and the interaction between drug group and study design.The results support the common clinical practice of including medications as part of a comprehensive psychoeducational treatment plan for some youth with maladaptive overt aggression within a variety of psychiatric disorders; however, not all referred youth respond to medication for overt aggression-related behavior, supporting the use of additional nonmedication interventions. Future pharmacological research should attempt to identify specific classes of psychiatric medications that are effective for specifically defined types of aggression in distinct psychiatric disorders.
Get full access to this article
View all access options for this article.
References
1.
*Aman, M.G., Marks, R.E., Turbott, S.H., Wilsher, C.P., & Merry, S.N. (1991). Clinical effects of methylphenidate and thioridazine in intellectually subaverage children. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 246—256.
2.
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author .
3.
*Anderson, L.T., Campbell, M., Adams, P.B., Small, A.M., Perry, R., & Shell, J. (1989). The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. Journal of Autism and Developmental Disorders, 19, 227—239.
4.
*Anderson, L.T., Campbell, M., Grega, D.M., Perry, R., Small, A.M., & Green, W.H. (1984). Haloperidol in the treatment of infantile autism: Effects on learning and behavioral symptoms. American Journal of Psychiatry, 141, 1195—1202.
5.
*Barrickman, L.L., Perry, P.J., Allen, A.J., Kuperman, S., Arndt, S.V., Herrmann, K.J., et al. (1995). Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 649—657.
6.
*Biederman, J., Baldessarini, R.J., Wright, V., Knee, D., & Harmatz, J.S. (1989). A double-blind placebo controlled study of desipramine in the treatment of ADD: I. Efficacy. Journal of the American Academy of Child and Adolescent Psychiatry, 28, 777— 784.
7.
*Black, B., & Uhde, T.W. (1994). Treatment of elective mutism with fluoxetine: A double-blind, placebo-controlled study. Journal of the American Academy of Child and Adolescent Psychiatry, 33, 1000—1006.
8.
Borduin, C.M. (1999). Multisystemic treatment of criminality and violence in adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 242— 249.
9.
Brestan, E.V., & Eyberg, S.M. (1998). Effective psychosocial treatments of conduct-disordered children and adolescents: Twenty-nine years, 82 studies, and 5,272 kids. Journal of Clinical Child Psychology, 27, 180—189.
10.
*Buitelaar, J.K., van der Gaag, R.J., Cohen-Kettenis, P., & Melman, C.T.M. (2001). A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. Journal of Clinical Psychiatry , 62(4), 239—248.
11.
*Campbell, M., Adams, P.B., Small, A.M., Kafantaris, V., Silva, R.R., Shell, J., et al. (1995). Lithium in hospitalized aggressive children with conduct disorder: A double-blind and placebo controlled study. Journal of the American Academy of Child and Adolescent Psychiatry , 34, 445—453.
12.
*Campbell, M., Small, A.M., Green, W.H., Jennings, S.J., Perry, R., Bennett, W.G., et al. (1984). Behavioral efficacy of haloperidol and lithium carbonate. Archives of General Psychiatry, 41, 650—656.
13.
*Carlson, G.A., Rapport, M.D., Pataki, C.S., & Kelly, K.L. (1992). Lithium in hospitalized children at 4 and 8 weeks: Mood, behavior, and cognitive effects. Journal of Child Psychology and Psychiatry, 33, 411— 425.
14.
*Casat, C.D., Pleasants, D.Z., & Van Wyck Fleet, J. (1987). A double-blind trial of bupropion in children with attention deficit disorder. Psychopharmacology Bulletin, 23(1), 120—122.
15.
*Clay, T.H., Gualtieri, C.T., Evans, R.W., & Gullion, C.M. (1988). Clinical and neuropsychological effects of the novel antidepressant bupropion. Psychopharmacology Bulletin , 24(1), 143—148.
16.
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum.
17.
*Conners, C.K., Casat, C.D., Gualtieri, C.T., Weller, E., Reader, M., Reiss, A., et al. (1996). Bupropion hydrochloride in attention deficit disorder with hyperactivity. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1314—1321.
18.
Connor, D.F. (2002). Aggression and antisocial behavior in children and adolescents: Research and treatment. New York: Guilford Press.
19.
*Connor, D.F., Barkley, R.A., & Davis, H.T. (2000). A pilot study of methylphenidate, clonidine, or the combination in ADHD co-morbid with aggressive oppositional defiant or conduct disorder. Clinical Pediatrics, 39(1), 15—25.
20.
Connor, D.F., Glatt, S.J., Lopez, I.D., Jack-son, D., & Melloni, R.H., Jr. (2002). Psychopharmacology and aggression: I. A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 253—261.
21.
Connor, D.F., Melloni, R.H., Jr., & Harrison, R.J. (1998). Overt categorical aggression in referred children and adolescents. Journal of the American Academy of Child Adolescent Psychiatry, 37(1), 66—73.
22.
Connor, D.F., Ozbayrak, K.R., Harrison, R.J., & Melloni, R.H., Jr. (1998). Prevalence and patterns of psychotropic and anticonvulsant medication use in children and adolescents referred to residential treatment. Journal of Child and Adolescent Psychopharmacology , 8(1), 27—38.
23.
Connor, D.F., Ozbayrak, K.R., Kusiak, K.A., Caponi, A.B., & Melloni, R.H., Jr. (1997). Combined pharmacotherapy in children and adolescents in a residential treatment center. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 248—254.
24.
Connor, D.F., & Steingard, R.J. (1996). A clinical approach to the pharmacotherapy of aggression in children and adolescents. Annals of the New York Academy of Sciences, 794, 290—307.
25.
*Cueva, J.E., Overall, J.E., Small, A.M., Armenteros, J.L., Perry, R., & Campbell, M. (1996). Carbamazepine in aggressive children with conduct disorder: A double-blind and placebo-controlled study. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 480—490.
26.
Dodge, K.A., & Coie, J.D. (1987). Social-information processing factors in reactive and proactive aggression in children's peer groups. Journal of Personality and Social Psychology, 53, 1146—1158.
27.
*Donovan, S.J., Stewart, J.W., Nunes, E.V., Quitkin, F.M., Parides, M., Daniel, W., et al. (2000). Divalproex treatment for youth with explosive temper and mood lability: A double-blind, placebo-controlled cross-over design . American Journal of Psychiatry, 157, 818—820.
28.
Durlak, J.A., Fuhrman, T., & Lampman, C. (1991). Effectiveness of cognitive-behavior therapy for maladapting children: A meta-analysis. Psychological Bulletin,110, 204— 214.
29.
*Emslie, G.J., Rush, A.J., Weinberg, W.A., Kowatch, R.A., Hughes, C.W., Carmody, T., et al. (1997). A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Archives of General Psychiatry, 54, 1031— 1037.
30.
Eveloff, H.H. (1966). Psychopharmacologic agents in child psychiatry . Archives of General Psychiatry,14, 472—481.
31.
*Findling, R.L., McNamara, N.K., Branicky, L.A., Schluchter, M.D., Lemon, E., & Blumer, J.L. (2000). A double-blind pilot study of risperidone in the treatment of conduct disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 509—516.
32.
Fish, B. (1969). Problems of diagnosis and the definition of comparable groups: A neglected issue in drug research with children. American Journal of Psychiatry,125, 271— 286.
33.
Frick, P.J., Lahey, B.B., Loeber, R., Tannenbaum, L., Van Horn, Y., Christ, M. A. G., et al. (1993). Oppositional defiant disorder and conduct disorder: A meta-analytic review of factor analyses and cross-validation in a clinical sample. Clinical Psychology Review, 13, 319—340.
34.
*Goldberg, J.B., & Kurland, A.A. (1974, February-March). Pimozide in the treatment of behavioral disorders of hospitalized adolescents. The Journal of Clinical Pharmacology, 14, 134—138.
35.
*Greenhill, L.L., Solomon, M., Pleak, R., & Ambrosini, P. (1985). Molindone hydrochloride treatment of hospitalized children with conduct disorder. Journal of Clinical Psychiatry , 46(8), 20—25.
36.
Henggeler, S.W., Clingempeel, W.G., Brondino, M.J., & Pickrel, S.G. (2002). Four-year follow-up of multisystemic therapy with substance-abusing and substance-dependent juvenile offenders. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 868—874.
37.
Henggeler, S.W., Melton, G.B., & Smith, L.A. (1992). Family preservation using multisystemic therapy: An effective alternative to incarcerating serious juvenile offenders. Journal of Consulting and Clinical Psychology, 60, 953—961.
38.
Hinshaw, S.P. (1987). On the distinction between attentional deficits/hyperactivity and conduct problems/aggression in child psychopathology. Psychological Bulletin,101, 443—463.
39.
*Hunt, R.D., Minderaa, R.B., & Cohen, D.J. (1985). Clonidine benefits children with attention deficit disorder and hyperactivity: Report of a double-blind placebo-cross-over therapeutic trial. Journal of the American Academy of Child and Adolescent Psychiatry, 24, 617—629.
40.
*Jaselskis, C.A., Cook, E.H., Fletcher, K.E., & Leventhal, B.L. (1992). Clonidine treatment of hyperactive and impulsive children with autistic disorder. Journal of Clinical Psychopharmacology, 12, 322—327.
41.
Kazdin, A.E. (1980). Research design in clinical psychology. New York: Harper & Row.
42.
Kazdin, A.E. (1995). Conduct disorders in childhood and adolescence . London: Sage.
43.
*Kumra, S., Frazier, J.A., Jacobsen, L.K., McKenna, K., Gordon, C.T., Lenane, M.C., et al. (1996). Childhood-onset schizophrenia: A double-blind clozapine-haloperidol comparison. Archives of General Psychiatry , 53, 1090—1097.
44.
*Leckman, J.F., Hardin, M.T., Riddle, M.A., Stevenson, J., Ort, S.I., & Cohen, D.J. (1991). Clonidine treatment of Gilles de la Tourette's syndrome. Archives of General Psychiatry, 48, 324—328.
45.
Lipsey, M.W., & Wilson, D.B. (2001). Practical meta-analysis: Vol. 49. Applied social research methods series. Thousand Oaks, CA: Sage.
46.
Loeber, R., & Schmaling, K.B. (1985). Empirical evidence for overt and covert patterns of antisocial conduct problems: A meta-analysis . Journal of Abnormal Child Psychology, 13, 337—352.
47.
*Malone, R.P., Delaney, M.A., Luebbert, J.F., Cater, J., & Campbell, M. (2000). A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder . Archives of General Psychiatry, 57, 649— 654.
48.
Mosteller, F.M., & Bush, R.R. (1954). Selected quantitative techniques. In G. Lindzey (Ed.), Handbook of social psychology: Vol. 1. Theory and method (pp. 289— 334). Cambridge, MA: Addison-Wesley.
49.
Mytton, J.A., DiGuiseppi, C., Gough, D.A., Taylor, R.S., & Logan, S. (2002). School-based violence prevention programs: Systematic review of secondary prevention trials. Archives of Pediatrics and Adolescent Medicine, 156, 752—762.
50.
*Naruse, H., Nagahata, M., Nakane, Y., Shirahashi, K., Takesada, M., & Yamazaki, K. (1982). A multi-center double-blind trial of pimozide (Orap), haloperidol and placebo in children with behavioral disorders, using cross-over design. Acta Paedopsychiatrica, 48(4), 173—184.
51.
*Perry, R., Campbell, M., Adams, P.B., Lynch, N., Spencer, E.K., Curren, E.L., et al. (1989). Long-term efficacy of haloperidol in autistic children: Continuous versus discontinuous drug administration. Journal of the American Academy of Child and Adolescent Psychiatry, 28, 87—92.
52.
*Prince, J.B., Wilens, T.E., Biederman, J., Spencer, T.J., Millstein, R., Polisner, D.A., et al. (2000). A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 10, 193—204.
53.
*Rifkin, A., Karajgi, B., Dicker, R., Perl, E., Boppana, V., Hasan, N., et al. (1997). Lithium treatment of conduct disorders in adolescents. American Journal of Psychiatry, 154, 554—555.
54.
Rosenthal, R. (1991). Meta-analytic procedures for social research. Newbury Park, CA: Sage.
55.
*Scahill, L., Chappell, P.B., Kim, Y.S., Schultz, R.T., Katsovich, L., Shepherd, E., et al. (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.
56.
Scott, S. (1998). Aggressive behaviour in childhood. British Medical Journal, 316, 202—206.
57.
*Sheard, M.H., Marini, J.L., Bridges, C.I., & Wagner, E. (1976). The effect of lithium on impulsive aggressive behavior in man. American Journal of Psychiatry, 133, 1409— 1413.
58.
Snedecor, G.W., & Cochran, W.G. (1989). Statistical methods. Ames: Iowa State University Press.
59.
Spencer, T., Biederman, J., & Wilens, T. (2000). Pharmacotherapy of attention deficit hyperactivity disorder. Child and Adolescent Psychiatric Clinics of North America, 9(1), 77—97.
60.
Tabachnic, B., & Fidell, L. (2001). Using multivariate statistics (4th ed.). Boston: Allyn & Bacon .
61.
*Van Bellinghen, M., & De Troch, C. (2001). Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: A double-blind, placebo-controlled pilot trial. Journal of Child and Adolescent Psychopharmacology, 11(1), 5—13.
62.
*Waizer, J., Polizos, P., Hoffman, S.P., Engelhardt, D.M., & Margolis, R.A. (1972). A single-blind evaluation of thiothixene with outpatient schizophrenic children. Journal of Autism and Childhood Schizophrenia, 2, 378—386.
63.
Werry, J.S. (1997). Severe conduct disorder— Some key issues . Canadian Journal of Psychiatry, 42, 577—583.
