 |
 |
|
|
|
Aggression is defined as outward destructive behaviour that results from the confluence of longer-term factors (for example, biological, psychological, personality, family, peer, school, and community), short-term influences (for example, internal states of anger, boredom, or intoxication), and situational variables (that is, conflict, opportunity, and blockage of goals or needs) (1). Violence is overt and intentional aggression that includes hitting, choking, kicking, throwing objects, using a weapon, forcing sex, verbally threatening, and destroying property. This behaviour impoverishes children’s relationships in various spheres of their lives. Aggressive behaviour in children is very common in referred samples. Aggressive and other antisocial behaviours typically account for up to 50% of all child and adolescent psychiatric referrals (2). Such children usually have a myriad of psychiatric, psychological, educational, legal, peer, and familial difficulties and impairments. Several effective psychosocial interventions are emerging (3). Consistently effective and safe psychotropic medications for childhood aggression have yet to be established. Owing to our incomplete understanding of the underlying pathophysiology of aggression, past medical treatments have been largely nonspecific. Aggression has been previously targeted for intervention as a symptom, with less attention to underlying cause or diagnosis. This has resulted in the use of many and varied agents, increasing the possibility of poor treatment outcomes and treatment-emergent side effects. One approach that has been used to circumvent this lack of specificity is diagnostic assessment to carefully identify primary and comorbid psychiatric or neuropsychiatric disorders. The most common diagnosis that clinicians tend to give to aggressive children is conduct disorder (CD). However, considering other diagnoses is imperative, because these are often overlooked, are less obvious, and are potentially more responsive to medical or psychotherapeutic intervention. Common diagnoses include attention-deficit hyperactivity disorder (ADHD), mood disorders, thought or psychotic disorders, and brain injury. Other diagnostic possibilities with childhood aggression include seizure disorder, posttraumatic stress disorder (PTSD), mental retardation, and autism spectrum disorders (4). Conduct DisorderCD is by far the most common diagnosis in children and adolescents who are referred for aggression (5). The Ontario Child Health Study found that 5.5% of all children suffered from this condition (6). The DSM-IV definition for CD is “a disruptive behavioural disorder that can feature fighting, bullying, cruelty, robbery, sexual coercion, firesetting, conning, truancy, and other legal or societal violations” (7). There can be substantial psychiatric comorbidity with CD (that is, ADHD, affective disorders, and thought disorder), most of which is detailed elsewhere in this review. Treatment of such concordant conditions will likely reduce morbidity. Psychotropic treatment alone, unfortunately, has not helped in CD. These youths have many needs that involve multiple modes of treatment, various professionals, and numerous systems of care and monitoring. Even so, a justifiable goal of medication is to reduce irritability, explosiveness, and impulsivity to facilitate response to psychosocial therapies. Several medications have been found useful in controlled studies of primary CD, and neuroleptics are most commonly used. The use of risperidone (up to 3.0 mg daily) was well tolerated and was superior to placebo in reducing aggression in 10 youths (8). Extrapyramidal side effects have not been a problem in this study or in past open studies (9), with the main difficulties appearing to have been weight gain and sedation. Haloperidol has been the most rigorously studied, despite associated neurological side effects (10). Several controlled studies have found lithium equivalent in efficacy to typical neuroleptics, with 1 study as the first known to produce positive results on an aggression rating scale (Overt Aggression Scale) (11). Dosages in the literature have ranged from 500 mg to 2100 mg daily, resulting in serum levels of 0.32 mEq/L to 1.79 mEq/L. Many subjects have experienced nausea, vomiting, enuresis, cognitive dulling, fatigue, and ataxia. Despite these effects, most authors generally considered lithium use as safe (10,11). However, there have been 2 negative studies published, one involving adolescent inpatients and the other outpatients (12,13). Clinicians have tried other mood stabilizers in treating CD. An open trial of carbamazepine was found to be effective in a small (n = 10) study of preadolescents with CD and explosive aggression (14). In this study, the average dosage was 630 mg daily, achieving a mean blood level of 6.2 µg/mL. Unfortunately, a later controlled study found that carbamazepine was not superior to placebo (15). Use of valproic acid in 12 of 15 children with oppositional defiant disorder (ODD) or CD did prove to decrease explosiveness and mood lability in a double-blind controlled study (16). Two controlled studies have found that methylphenidate decreases aggression without the presence of ADHD (17,18). In Klein’s study, the dosage range was up to 60 mg daily, and Gadow’s paper found that 0.3 mg/kg was an effective dose. Yet, other studies have reported mixed findings (19). Other medications that were tried in open studies include clonidine, benzodiazepines, and trazodone. An open trial of clonidine in 17 aggressive children found a decrease in aggression with treatment, possibly correlated with plasma gamma-aminobutyric acid (GABA) levels (20). A randomized controlled trial found some effect on aggression with chlordiazepoxide, but concerns were raised about dependence and disinhibition in children (21). Trazodone in an open trial of 22 hospitalized children helped to reduce impulsivity and aggression, and this effect seemed to persist on follow-up several months later (22). To summarize, clinicians should attempt psychosocial interventions first or in conjunction with psychopharmacological strategies (23). If no obvious comorbidity exists, then the literature does, in a limited way, support the use of various agents. These include efficacy in controlled studies of risperidone, haloperidol, lithium, valproate, and methylphenidate. Efficacy has also been found in open trials of clonidine, trazodone, and carbamazepine. Some suggest that aggression associated with explosiveness or impulsivity may respond better to medication than would instrumental (premeditated) aggression or more covert behaviours (for example, conduct symptoms of lying, stealing, cheating, and rule violations). However, more controlled research and larger clinical trials would help. Attention-Deficit Hyperactivity DisorderADHD is second only to CD in frequency of diagnosis in aggressive children (24). ADHD occurs concomitantly with CD in 30% to 50% of cases (25). Despite extensive comorbidity, clinicians advise some caution in attributing inattention, hyperkinetic states, and impulsivity to ADHD only. These can also occur in bipolar disorder (BD) or dissociative disorders. Clearly, psychostimulants—predominantly methylphenidate—have proven efficacy in the core symptoms of ADHD. Over 70% of children have collectively responded in over 150 controlled studies (26). There have been several controlled studies in the literature that evaluated the effect of methylphenidate on aggression in children with ADHD. The largest study was conducted by Klein (18), wherein two-thirds of the 84 children met criteria for CD and ADHD. These children responded to up to 60 mg of methylphenidate for the 5-week trial, and ADHD did not necessarily need to be present for therapeutic effect. Some negative findings, however, have been reported (27,28). In the first, Hinshaw found no significant effects of 0.3 mg/kg of methylphenidate on anger and verbal or physical aggression in children with ADHD. In the second, Matier noted no changes in impulsivity in aggressive or in nonaggressive children with ADHD. Dextroamphetamine has also been used in small trials. Winsberg used dextroamphetamine (20 mg twice daily) and also reported effect in aggressive and hyperactive children (29). Amery used 15 mg to 30 mg daily and reported decreased aggressive behaviours (30). Other medications have also been studied in aggressive ADHD. Previous controlled studies of clonidine use in ADHD found positive effects (31). Connor conducted one of the few studies on clonidine in 24 ADHD children who were also aggressive (32). This group found that clonidine, in doses up to 0.3 mg daily, was effective with or without concurrent methylphenidate use. Yet, because of the small statistical power, a direct comparison between clonidine and methylphenidate could not be done. Side effects involving fine motor control were noted with clonidine. Guanfacine acts similarly but more selectively on alpha 2A receptors. It has a longer half-life and is less sedating. Hunt found that, in 13 children, guanfacine reduced hyperactive and immature behaviours in children with CD and ADHD (33). With respect to antidepressants, bupropion has been reported in a controlled study to reduce disruptive behaviour and aggression in 30 prepubertal children with ADHD (34). Tricyclic antidepressants, particularly desipramine, have been useful in ADHD generally, but not specifically in aggressive children with the disorder (35). Fluoxetine or sertraline, in combination with methylphenidate, has been found to reduce irritability and conduct behaviours in ADHD that is comorbid with depression (36). In fact, an open trial found efficacy for fluoxetine alone in ADHD (37). Aggressive CD, however, has not been studied specifically in this respect. Likewise, venlafaxine has not specifically been used in aggressive ADHD, but a low dosage (mean 60 mg daily) was useful in some children to reduce behavioural but not cognitive ADHD symptoms (38). Controlled studies of neuroleptics have found that aggression in children with ADHD responded to thioridazine, chlorpromazine, and haloperidol. Stimulants, however, have been found to be more effective with fewer side effects. Interestingly, case reports suggest that neuroleptics have combined successfully with psychostimulants in ADHD cases with atypical psychosis (39). Hence, more controlled studies exist for ADHD than for CD. These suggest efficacy in aggressive ADHD for methylphenidate, clonidine, bupropion, and some neuroleptics (for example, thioridazine, chlorpromazine, and haloperidol). Yet, mixed results (with methylphenidate) and concerns about side effects (with neuroleptics) do complicate clinical practice. With respect to open studies, guanfacine and dextroamphetamine have been useful in children with ADHD and aggressive behaviour. With comorbid depression, sertraline or fluroxetine with methylphenidate may benefit, but this combination is understudied. Venlafaxine and desipramine may have general ADHD effects but have not yet shown specific antiaggressive effects. However, the small numbers of studies, the number of patients in trials, and the largely uncontrolled nature of the research require some caution in interpretation. Mood and Anxiety DisordersBDs in childhood and adolescence have an estimated prevalence of about 1% (40). Of relevance, nearly 6% of this sample had experienced a distinct period of abnormally and persistently elevated, expansive, or irritable mood without fulfilling full BD criteria. Childhood BD can closely resemble disruptive behaviour disorders (that is, ADHD, CD, and ODD) and therefore can be easily overlooked (41). Irritability, explosiveness, mixed states, rapid cycling, suicidality, academic underachievement, substance use, illegal activities, aggression, and family psychiatric history typically characterize the clinical presentation, although this has been an area of some controversy. In one of the few well-controlled studies, Geller studied 25 adolescents with BD and comorbid substance abuse. Aggression, however, was not specifically studied. She found that 6 weeks of lithium treatment yielded clinically significant functional improvement and reduction in substance abuse (42). Lithium has generally been used in a dosage range of 600 mg to 2100 mg in 2 or 3 divided doses daily to yield a serum level of 0.6 mEq/L to 1.4 mEq/L. A dosage of 30 mg/kg daily, at least in preadolescents, has also been suggested as a guideline (43). Possible adverse effects in children have included nausea, diarrhea, vomiting, polyuria, headache, sedation, tremor, weight gain, and hypothyroidism (44). Similarly, controlled studies about the use of other mood stabilizers in aggressive children with BD are severely lacking. Of these, an open study found that valproate decreased aggression in 36 hospitalized adolescents with various diagnoses, principally BD (45). Another small, uncontrolled study that included 11 adolescents found that valproate had a positive effect on aggression in adolescent mania (46). Typical initial target dosages found useful for acute adolescent mania are in the range of 1000 mg to 2500 mg (44). In addition, 20 mg/kg daily has also been suggested as a guideline (47); this should ideally yield a serum level of 50 µg/mL to 100 µg/mL. Adverse effects in children may include nausea, weight gain, hepatotoxicity, and thrombocytopenia. Risperidone has been of some interest, but controlled trials, particularly in childhood aggressive BD, are lacking. In fact, one chart review found a positive effect on aggression in 28 youths with BD with largely mixed states. Of these, 82% improved in their manic and aggressive symptoms and 69% in their psychotic features, but only 8% showed a significant decline in ADHD symptoms (48). The mean (SD) dosage was 1.7 (1.3) mg daily. Another open study did find risperidone useful in comorbid mood disorder and aggression (49). Epidemiologic studies have found that depressive or dysthymic symptoms are comorbid with CD or ODD in 21% to 83% of clinical and community samples; depression coexisting with ADHD has been found in up to 57% of children (50). Children who suffered from depression had greater cognitive difficulties in controlling their anger. Male children, in particular, had core symptoms of irritability and aggression that were congruent with depressive disorders (51). Aggressive boys with ADHD had more symptoms of depression than did boys with ADHD and no aggression. As a result, these boys reported more depression than did control subjects (52). Aside from the previously mentioned study of fluoxetine and sertraline use in children with ADHD and depression, studies of selective serotonin reuptake inhibitors (SSRIs) in aggressive children with depression are lacking. One open trial with psychiatric adolescent inpatients found no benefit from SSRIs on aggression (53). Trazodone, however, has reduced aggressivity and impulsivity in inpatient psychiatric children with disruptive behaviours (54). Buspirone has been used for generalized anxiety. One open study of 19 hospitalized children with aggression and anxiety found decreased aggression and need for restraint. Conversely, 4 individuals exhibited increased aggression (55). Hence, an increasing armamentarium of psychotropics is showing evidence of effect in child and adolescent mood and anxiety conditions, although largely in open trials and small studies. Studies that look at the construct of aggression in this context are lacking but, hopefully, will be a focus of future research. Other ConditionsImportantly, most children and adolescents with psychosis or who suffer from a psychotic disorder are not violent. However, the more violent youths are, the more likely they have psychotic, particularly paranoid, features (56). Unfortunately, controlled studies of medication interventions specifically for aggression in these populations have not been done, despite many studies on both typical and atypical neuroleptics in childhood-onset schizophrenia, far less related psychotic spectrum conditions. Interestingly, the adult literature is finding increasing evidence of beta blocker use (such as, nadolol), especially as an adjunct for reducing aggression in adults with psychotic disorders (57). Similarly, children with organic brain syndromes, such as traumatic brain injury, may exhibit aggressiveness, explosiveness, and irritability. Propanolol in dosages up to 960 mg daily has been used in children and adolescents with prominent rage outbursts, some of whom met criteria for intermittent explosive disorder. Most received between 80 mg and 320 mg daily (58). Propanolol has also been found to help in an open trial of children with acute PTSD, who may be vulnerable to aggression, owing to hostility, irritability, impulsivity, and sympathetic overdrive (59). Controlled studies in subjects who suffer from mental retardation support the use of chlorpromazine, thioridazine, haloperidol, pimozide, methylphenidate, and more recently, risperidone for aggression (4,60). Open studies have found some effects from propanolol, nadolol, lithium, carbamazepine, buspirone, and fluoxetine in this population (4). Risperidone has also been useful in children with Tourette syndrome and aggression in an open, retrospective trial (61). For autism spectrum conditions, haloperidol has the most evidence of effect in controlled studies (62,63). In addition, a small controlled study supported use of clomipramine for anger attacks (64); other medications generally useful in this group include trifluoperazine, fluphenazine, thiothixene, molindone, clonidine, fluoxetine, buspirone, propanolol, and nadolol (4).
SummaryAggressive behaviour is extremely common in the clinical child and adolescent population. Psychiatric evaluation should be part of a comprehensive multidisciplinary assessment that encompasses medical, neurological, psychological, psychosocial, familial, and academic domains. Accordingly, clinicians should provide multimodal treatment to address the many vulnerabilities. The differential diagnosis of childhood aggression includes CD, ADHD, BD, depression, psychotic disorders, traumatic brain injury, intermittent explosive disorder, PTSD, mental retardation, autism spectrum disease, and dissociative disorders. Such a diagnostic assessment can lead the clinician toward possible psychopharmacological approaches (Table 1). If the general child psychopharmacology literature is thought to be in its infancy, then the relevant literature on child aggression is most likely best characterized as “postnatal.” Nevertheless, some evidence exists to guide psychotropic choice in certain conditions, but children and youths are complex beings with much comorbidity. Hence, there may at this point be more art than science in medical intervention, especially as polypharmacy is a current and likely future trend. More controlled studies, larger sample sizes, more diagnostic specificity, standardized measures of aggression, and longer follow-up studies are needed. Only then will we be more scientifically informed about evidence-based approaches in this complex and challenging area. References1. Bassarath L. Conduct disorder: a biopsychosocial review. Can J Psychiatry 2001;46:609–16. 2. Kazdin AE. Conduct disorder in childhood and adolescence. 2nd ed. Thousand Oaks (CA): Sage; 1995. 3. Frick PJ. Effective interventions for children and adolescents with conduct disorder. Can J Psychiatry 2001;46:597–608. 4. Connor DF, Steingard RJ. A clinical approach to the pharmacotherapy of aggression in children and adolescents. Ann N Y Acad Sci 1996;794:290–307. 5. Kazdin AE. Treatment of antisocial behaviour in children and adolescents. Homewood (IL): Dorsey; 1985. 6. Offord DR, Boyle MH, Fleming JE, Munroe Blum H, Rae-Grant NI. Ontario Child Health Study: summary of selected results. Can J Psychiatry 1989;34:483–91. 7. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): American Psychiatric Association; 1994. 8. Findling RL, McNamara NK, Branicky LA, Schluchter MD, Lemon E, and Blumer JL. A double-blind pilot study of risperidone in treatment of conduct disorder. J Am Acad Child Adolesc Psychiatry 2000;39:4:509–16. 9. Buitelaar JK. Open-label treatment with risperidone of 26 psychiatrically hospitalized children and adolescents with mixed diagnoses and aggressive behavior. J Child Adolesc Psychopharmacol 2000;10:19–26. 10. Campbell M, Small AM, Green WH, Jennings SJ, Perry R, Bennett WG, and others. Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorder. Arch Gen Psychiatry 1984;41:650–6. 11. Malone RP, Delaney MA, Luebbert JF, Cater J, Campbell M. A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder. Arch Gen Psychiatry 2000;57:649–54. 12. Rifkin A, Karajgi B, Dicker R, Perl E, Boppana V, Hasan N, and others. Lithium treatment of conduct disorders in adolescents. Am J Psychiatry 1997;154:554–5. 13. Klein RG. Preliminary results: lithium effects in conduct disorders. CME Syllabus and Proceedings Summary, Symposium 2. The 144th Annual Meeting of the American Psychiatric Association; 1991 May 11–16; New Orleans (LA). Washington (DC): American Psychiatric Association. p. 119–120. 14. Kafantaris V, Campbell M, Padron-Gayol MV, Small AM, Locascio JJ, Rosenberg CR. Carbamazepine in hospitalized aggressive conduct disorder children: an open pilot study. Psychopharmacol Bull 1992;28:193–9. 15. Cueva JE, Overall JE, Small AM, Armenteros JL, Perry R, Campbell M. Carbamazepine in aggressive children with conduct disorder: a double-blind and placebo-controlled study. J Am Acad Child Adolesc Psychiatry 1996;35:480–90. 16. Donovan SJ, Stewart JW, Nunes EV, Stewart JW, Quitkin FM, Parides M. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Am J Psychiatry 2000;157:818–20. 17. Gadow KD, Nolan EE, Sverd J, Sprafkin J, Paolicelli L. Methylphenidate in aggressive-hyperactive boys: I. Effects on peer aggression in public school settings. J Am Acad Child Adolesc Psychiatry 1990;29:710–8. 18. Klein RG, Abikoff H, Klass E, Ganeles D, Seese LM, Pollack S. Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Arch Gen Psychiatry 1997;54:1073–80. 19. Campbell M, Gonzalez NM, Silva RR. The pharmacologic treatment of conduct disorders and rage outbursts. Psychiatr Clin North Am 1992;15:69–85. 20. Kemph JP, DeVane CL, Levin GM, Jarecke R, Miller RL. Treatment of aggressive children with clonidine: results of an open pilot study. J Am Acad Child Adolesc Psychiatry 1993;32:577–81. 21. Petti TA, Fish B, Shapiro T, Cohen IL, Campbell M. Effects of chlordiazepoxide in disturbed children: a pilot study. J Clin Psychopharmacol 1982;2:270–3. 22. Zubieta JK, Alessi NE. Acute and chronic administration of trazodone in the treatment of disruptive behavior disorders in children. J Clin Psychopharmacol 1992;12:346–51. 23. Frick PJ. Effective interventions for children and adolescents with conduct disorder. Can J Psychiatry 2001;46:597–608. 24. Offord DR, Boyle MH, Racine YA. The epidemiology of antisocial behavior in childhood and adolescence. In: Pepler DJ, Rubin KH, editors. The development and treatment of childhood aggression Hillsdale (NJ): Lawrence Erlbaum; 1991. p 21–54. 25. Biederman J, Faraone SV, Lapey K. Child and Adolescent Psychiatric Clinics of North America 1992;1:335–60. 26. Barkley RA. Attention-deficit hyperactivity disorder: a handbook for diagnosis and treatment. 2nd ed. New York: Guilford Press; 1998. 27. Hinshaw SP, Henker B, Whalen CK. Self-control in hyperactive boys in anger-inducing situations: effects of cognitive-behavioral training and of methylphenidate. J Abnorm Child Psychol 1984;12:155–77. 28. Matier K, Halperin JM, Sharma V, Newcorn JH, Sathaye N. Methylphenidate response in aggressive and nonaggressive ADHD children: distinctions on laboratory measures of symptoms. J Am Acad Child Adolesc Psychiatry 1992;31:219–25. 29. Winsberg BG, Press M, Bialer I, Kupietz S. Dextroamphetamine and methylphenidate in the treatment of hyperactive-aggressive children. Pediatrics 1974;53:236–41. 30. Amery B, Minichiello MD, Brown GL. Aggression in hyperactive boys: response to D-amphetamine. J Am Acad Child Psychiatry 1984;23:291–4. 31. Hunt RD, Minderaa RB, Cohen DJ. Clonidine benefits children with attention deficit disorder and hyperactivity: report of a double-blind placebo-crossover therapeutic trial. J Am Acad Child Psychiatry 1985;24:617–29. 32. Connor 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. 33. Hunt RD, Arnsten AF, Asbell MD. An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995;34:50–4. 34. Clay TH, Gualtieri CT, Evans RW, Gullion CM. Clinical and neuropsychological effects of the novel antidepressant bupropion. Psychopharmacol Bull 1988;24:143–8. 35. Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS. A double-blind placebo controlled study of desipramine in the treatment of ADD: I. Efficacy. J Am Acad Child Adolesc Psychiatry 1989;28:777–84. 36. Findling RL. Open-label treatment of comorbid depression and attentional disorders with co-administration of serotonin reuptake inhibitors and psychostimulants in children, adolescents, and adults: a case series. J Child Adolesc Psychopharmacol 1996;6:165–75. 37. Barrickman L, Noyes R, Kuperman S, Schumacher E, Verda M. Treatment of ADHD with fluoxetine: a preliminary trial. J Am Acad Child Adolesc Psychiatry 1991;30:762–7. 38. Olvera RL, Pliszka SR, Luh J, Tatum R. An open trial of venlafaxine in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. J Child Adolesc Psychopharmacol 1996;6:241–50. 39. Pine DS, Klein RG, Lindy DC, Marshall RD. Attention-deficit hyperactivity disorder and comorbid psychosis: a review and two clinical presentations. J Clin Psychiatry 1993;54:140–5. 40. Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorders in a community sample of older adolescents: prevalence, phenomenology, comorbidity, and course. J Am Acad Child Adolesc Psychiatry 1995;34:454–63. 41. Carlson GA. Clinical features and pathogenesis of child and adolescent mania. In: Shulman KI, Tohen M, Kutcher SP, editors. Mood disorders across the life span. New York: Wiley-Liss; 1996. p. 127–47. 42. Geller B, Cooper TB, Sun K, Zimerman B, Frazier J, Williams M, and others. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry 1998;37:171–8. 43. Weller EB, Weller RA, Fristad MA. Lithium dosage guide for prepubertal children: a preliminary report. J Am Acad Child Psychiatry 1986;25:92–5. 44. Sadock BJ, Kaplan VA. Pocket handbook of clinical psychiatry. 3rd ed. . Philadelphia: Lippincott Williams and Wilkins; 2001. p 275–305. 45. Deltito JA, Levitan J, Damore J, Hajal F, Zambenedetti M. Naturalistic experience with the use of divalproex sodium on an in-patient unit for adolescent psychiatric patients. Acta Psychiatr Scand 1998;973:236–40. 46. West SA, Keck PE, McElroy SL, Strakowski SM, Minnery KL, McConcille BJ, and others. Open trial of valproate in the treatment of adolescent mania. J Child Adolesc Psychopharmacol 1994;4:263–7. 47. Kutcher SP. Affective disorders in children and adolescents: a critical clinically relevant review. In: Walsh BT, editor. Child psychopharmacology. American Psychiatric Association Review of Psychiatry. Volume 17. Washington (DC); APA; 1998. p 91–114. 48. Frazier JA, Meyer MC, Biederman J, Wozniak J, Wilens TE, Spencer TJ, and others. Risperidone treatment for juvenile bipolar disorder: a retrospective chart review. J Am Acad Child Adolesc Psychiatry 1999;38:960–5. 49. Scheier HA. Risperidone for young children with mood disorders and aggressive behaviour. J Child Adolesc Psychopharmacol 1998;8:49–59. 50. Angold A, Costello EJ. Depressive comorbidity in children and adolescents: empirical, theoretical, and methodological issues. Am J Psychiatry 1993;150:1779–91. 51. Kashani JH, Dahlmeier JM, Borduin CM, Soltys S, Reid JC. Characteristics of anger expression in depressed children. J Am Acad Child Adolesc Psychiatry 1995;34:322–6. 52. Treuting JJ, Hinshaw SP. Depression and self-esteem in boys with attention- deficit/hyperactivity disorder: associations with comorbid aggression and explanatory attributional mechanisms. J Abnorm Child Psychol 2001;29:23–39. 53. Constantino JN, Liberman M, Kincaid M. Effects of serotonin reuptake inhibitors on aggressive behaviour in psychiatrically hospitalized adolescents: results of an open trial. J Child Adolesc Psychopharmacol 1997;7:31–44. 54. Zubieta JK, Alessi NE. Acute and chronic administration of trazodone in the treatment of disruptive behaviour disorders in children. J Clin Psychopharmacol 1992:12:346–51. 55. Pfeffer Cr, Jiang H, Domeshek LJ. Buspirone treatment of psychiatrically hospitalized prepubertal children with symptoms of anxiety and moderately severe aggression. J Child Adolesc Psychopharmacol 1997;7:145–55. 56. Lewis DO, Lovely R, Yeager C, Della Femina D. Toward a theory of the genesis of violence: a follow-up study of delinquents. J Am Acad Child Adolesc Psychiatry 1989;28:431–6. 57. Allan ER, Alpert M, Sison CE, Citrome L, Laury G, Berman I. Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients. J Clin Psychiatry 1996;57:455–9. 58. Williams DT, Mehl R, Yudofsky S, Adams D, Roseman B. The effect of propranolol on uncontrolled rage outbursts in children and adolescents with organic brain dysfunction. J Am Acad Child Psychiatry 1982;21:129–35. 59. Famularo R, Kinscherff R, Fenton T. Propranolol treatment for childhood posttraumatic stress disorder, acute type. A pilot study. Am J Dis Child 1988;142:1244–7. 60. Van Bellinghen M, De Troch C. Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: a double-blind, placebo-controlled pilot trial. J Child Adolesc Psychopharmacol 2001;11:5–13. 61. Sandor P, Stephens RJ. Risperidone treatment of aggressive behaviour in children with Tourette syndrome [letter]. J Clin Psychopharmacol 2000;20:710–2. 62. 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;19:227–39. 63. Joshi PT, Capozzoli JA, Coyle JT. Low-dose neuroleptic therapy for children with childhood-onset pervasive developmental disorder. Am J Psychiatry 1988;145:335–8. 64. Gordon CT, State RC, Nelson J, Hamburger SD, Rapoport JL. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry 1993;50:441–7. Author(s)Manuscript received October 2002 and accepted January 2003. 1. Staff Psychiatrist, Centre for Addiction and Mental Health, Toronto, Ontario. Address for correspondence: Dr L Bassarath, Centre for Addiction and Mental Health, 250 College Street, Suite 307, Toronto ON M5T 1R8
1 | 2
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||