Evidence-Based Reviews

How to reduce aggression in youths with conduct disorder

Current Psychiatry. 2004 April;3(4):65-79

References

1. Prescribing psychoactive medications for children and adolescents American Academy of Child and Adolescent Psychiatry policy statement, adopted Sept. 20, 2001. Available at:http://www.aacap.org/publications/policy/ps41.htm Accessed Jan. 15, 2004.

2. Pappadopulos E, MacIntyre JC, Crismon ML, et al. Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part II. J Am Acad Child Adolesc Psychiatry 2003;42(2):145-61.

3. Hollander E, Tracy KA, Swann AC, et al. Divalproex in the treatment of impulsive aggression: efficacy in Cluster B personality disorders. Neuropsychopharmacology 2003;28:1186-97.

4. Physician’s Desk Reference (57th ed). Montvale, NJ: Thomson Healthcare, 2003.

5. Aman MG, DeSmedt G, Derivan A, et al. Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence. Am J Psychiatry 2002;159:1337-46.

6. Snyder R, Turgay A, Aman M, et al. Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. J Am Acad Child Adolesc Psychiatry 2002;41(9):1026-36.

7. Findling RL, McNamara NK, Branicky LA, et al. A double-blind pilot study of risperidone in the treatment of conduct disorder. J Am Acad Child Adolesc Psychiatry 2000;39:509-16.

8. Malone RP, Maislin G, Choudhury MS, et al. Risperidone treatment in children and adolescents with autism: short- and long-term safety and effectiveness. J Am Acad Child Adolesc Psychiatry 2002;41(2):140-7.

9. Sheard MH, Marini JL, Bridges CI, Wagner E. The effect of lithium on impulsive aggressive behavior in man. Am J Psychiatry 1976;133(12):1409-13.

10. 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;34:445-53.

11. Malone RP, Delaney MA, Luebbert JF, et al. A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder. Arch Gen Psychiatry 2000a;57(7):649-54.

12. Yudofsky SC, Silver JM, Jackson W, et al. The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psychiatry 1986;143:35-9.

13. Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically-based behavioral assessments of impulsive aggressive behavior. J Neuropsychiatry 1991;3:S44-S5.

14. Malone RP, Delaney MA, Gifford C. Adverse events during lithium treatment in children varies by setting. Miami Beach, FL: American Academy of Child and Adolescent Psychiatry annual meeting, 2003.

15. Rifkin A, Karajgi B, Dicker R, et al. Lithium treatment of conduct disorders in adolescents. Am J Psychiatry 1997;154:554-5.

16. Klein RG. Preliminary results: lithium effects in conduct disorders. New Orleans: American Psychiatric Association annual meeting, 1991.

17. Zito JM, Safer DJ, DosReis S, et al. Psychotropic practice patterns for youth: a 10-year perspective. Arch Pediatr Adolesc Med 2003;157:17-25.

18. Malone RP, Delaney MA. Psychopharmacologic interventions in children with aggression: neuroleptics, lithium, and anticonvulsants. In: Coccaro EF (ed). Aggression: assessment and treatment. New York: Marcel Dekker, 2003b;331-49.

19. Donovan SJ, Stewart JW, Nunes EV, et al. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Am J Psychiatry 2000;157:818-20.

20. Steiner H. A randomized clinical trial of divalproex sodium in conduct disorders. J Clin Psychiatry (in press).

21. Isojarvi JT, Laatikainen TJ, Knip M, et al. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996;39:579-84.

22. MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention deficit/hyperactivity disorder. Arch Gen Psychiatry 1999;56:1073-86.

23. Conner DF, Barkley RA, Davis HT. A pilot study of methylphenidate, clonidine, or the combination in ADHD comorbid with aggressive oppositional defiant or conduct disorder. Clin Pediatr 2000;39:15-25.

24. Hazell PL, Stuart JE. A randomized controlled trial of clonidine added to psychostimulant medication for hyperactive and aggressive children. J Am Acad Child Adolesc Psychiatry. 2003;886-94.

25. Armenteros JL, Lewis JE. Citalopram treatment for impulsive aggression in children and adolescents: an open pilot study. J Am Acad Child Adolesc Psychiatry 2002;41:522-9.

Anticonvulsants

Anticonvulsants have been used to decrease aggression for more than 50 years, and epidemiologic data show their use is increasing markedly.¹⁷ Few controlled studies support this prescribing trend, however.¹⁸

Initial reports suggested that anticonvulsants reduce disruptive behaviors, but more-critically designed studies have not supported this finding. For example, phenytoin sodium (diphenylhydantoin) demonstrated efficacy in open trials, but controlled trials found this anticonvulsant no more effective than placebo. In fact, placebo may have reduced aggression more than the active drug. Likewise, earlier controlled trials of carbamazepine indicated efficacy, but more-carefully designed trials using specific measures of aggression did not.

Divalproex is the anticonvulsant most commonly used for aggression in children and adolescents. Only one small, placebo-controlled study has found it effective in reducing aggression in children.¹⁹

Twenty children ages 10 to 18 with conduct disorder or oppositional defiant disorder were randomized to divalproex, 750 to 1,500 mg/d, or placebo. Eighteen completed the first phase, and 15 crossed over to the other treatment. Concomitant drug treatment, including stimulants, was allowed. The authors reported that 12 of 15 subjects showed some response to divalproex.

A 7-week study compared divalproex in high dosages (up to 1,500 mg/d) versus low dosages (up to 250 mg/d). This study was not placebo-controlled, but aggression was reduced more in the high-dosage than in the low-dosage group.²⁰

Recommendation. If you use an anticonvulsant, first obtain informed consent from the patient and parent. Divalproex causes weight gain and has been associated with increased risk of polycystic ovary syndrome with masculinizing effects.²¹

Double-blind, placebo-controlled studies of divalproex and other anticonvulsants in treating aggression are needed, particularly as prescriptions for these agents are rising.

Stimulants

Some small controlled studies suggest that stimulants can reduce aggression in children with ADHD, but their effects on aggression in conduct disorder have not been well studied. Aggression was not measured directly in the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD.²¹ Most other studies have been small and included children with ADHD but not necessarily conduct disorder.

Recommendation. Stimulants may help reduce aggression in children with ADHD, but studies gauging their effects in conduct disorder are needed.

Alpha agonists

Alpha agonists such as clonidine and guanfacine are increasingly being used to treat children with disruptive disorders, despite limited evidence. The small controlled studies that examined alpha agonists as monotherapy or add-ons in this population did not directly measure aggression.^22,23

Recommendation. Little data support alpha agonists for reducing aggression. They should probably be considered second-line treatment.

SSRIs

No double-blind, placebo-controlled studies have tested any selective serotonin reuptake inhibitor (SSRIs) for reducing aggression in conduct disorder. In a 6-week open study, citalopram (mean 27 mg/d) reduced impulsive aggression in 12 children with mixed diagnoses, as measured by the modified OAS,¹³ Child Behavior Checklist, and CGI.²⁴

Recommendation. Use caution when prescribing SSRIs to aggressive youth, as these drugs may contribute to aggression in some mood-disordered children. More evidence of SSRIs’ safety and efficacy in this population is needed.

Related resources

Overt Aggression Scale. In: Coccaro EF, Harvey PD, Kupsaw-Lawrence E, et al. Development of neuropharmacologically-based behavioral assessments of impulsiveaggressive behavior. J Neuropsychiatry 1991;3(2):S44-S51.

Drug brand names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Citalopram • Celexa
Chlorpromazine • Thorazine
Clonidine • Catapres
Phenytoin sodium • Dilantin
Divalproex • Depakote
Guanfacine • Tenex
Haloperidol • Haldol
Olanzapine • Zyprexa
Quetiapine • Seroquel
Risperidone • Risperdal
Thioridazine • Mellaril
Ziprasidone • Geodon

Disclosure

Dr. Malone receives research support from Pfizer Inc. and Eli Lilly and Co. and is a consultant to Janssen Pharmaceutica.

Dr. Delaney is a consultant to Shire Pharmaceuticals.

Dr. Sheikh reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.