Pharmacologic Management of Aggression in Adults with Intellectual Disability
DOI:
https://doi.org/10.6000/2292-2598.2013.01.01.5Keywords:
Intellectual disability, mental retardation, treatmentAbstract
Introduction: Aggression is a common behavioral problem seen in patients with intellectual disabilities (ID). The safety and efficacy of second generation antipsychotics (SGAs), mood stabilizers and antidepressants in the management of aggression in these individuals have minimally been studied. This review aims to 1) summarize the studies conducted using second generation antipsychotics, mood stabilizers and antidepressants in treating aggressive behaviors in patient with ID and 2) determine based on the existing literature, which medications have been examined in the most rigorous study design that might suggest the most efficacy for use in clinical practice.
Methods: Literature searches using PUBMED Central, CINAHL Plus, PsychINFO, and Embase databases were conducted using the following terms: intellectual disability/disabilities, mental retardation, developmental disability/disabilities, aggression, agitation, behavior disorder, adult, treatment, management. Studies predominantly including children with ID, and autism/pervasive developmental disabilities spectrum disorders were excluded. Analyses were done by class of medication: SGAs, mood stabilizers and antidepressants. The primary outcome measure was reduction in aggressive or self injurious behaviors as measured by each individual study.
Results: The most rigorous study designs found using these agents were randomized controlled trials (RCT). A total of 10 RCTs were found, the majority being with risperidone (3) and lithium (2). Treatment with risperidone showed reduction in aggression when compared to placebo in most RCTs with the exception of one study in which risperidone was not better than placebo. Both lithium studies showed reduction in aggression when compared to placebo. The most abundant literature exists in retrospective chart reviews. The most commonly studied agent was risperidone which showed reduction in aggression in majority of the studies.
Conclusions: Limited data exists for treatment of aggression in adults with ID. There are very few studies examining pharmacologic agents using RCTs. Given that risperidone and lithium were the most commonly studied agents in the most rigorous experimental design, it is suggested that these two agents prove efficacious for treatment of aggression in patients with ID. Limitations to most of these studies included concomitant psychotropic administration with variations in types and dosing, severity of ID, and the idea that a wide variety of aggression scales were used to assess outcome. Further research with more scientific rigor is required in this field.
References
Lindenmayer JP. The pathophysiology of agitation. J Clin Psychiatry 2000; 61(Suppl 14): 5-10.
Lakin KC, Hill BK, Hauber FA, et al. New admissions and readmissions to a national sample of public residential facilities. Am J Ment Defic 1983; 88(1): 13-20.
Aman MG, Richmond G, Stewart AW, Bell JC, et al. The aberrant behavior checklist: factor structure and the effect of subject variables in American and New Zealand facilities. Am J Ment Defic 1987; 91(6): 570-8.
Tsiouris, JA. Pharmacotherapy for aggressive behaviours in persons with intellectual disabilities: treatment or mistreatment? J Intellect Disabil Res 2010; (54)part 1: 1-16. DOI: https://doi.org/10.1111/j.1365-2788.2009.01232.x
Cooper SA, Smiley E, Jackson A, et al. Adults with intellectual disabilities: prevalence, incidence and remission of aggressive behaviour and related factors. J Intellect Disabil Res 2009; 53(3): 217-32. http://dx.doi.org/10.1111/j.1365-2788.2008.01127.x DOI: https://doi.org/10.1111/j.1365-2788.2008.01127.x
Emerson E, Kiernan C, Alborz A, et al. The prevalence of challenging behaviors: a total population study. Res Dev Disabil 2001; 22(1): 77-93. http://dx.doi.org/10.1016/S0891-4222(00)00061-5 DOI: https://doi.org/10.1016/S0891-4222(00)00061-5
Meins W. Symptoms of major depression in mentally retarded adults. J Intellect Disabil Res 1995; 39(1): 41-45. http://dx.doi.org/10.1111/j.1365-2788.1995.tb00912.x DOI: https://doi.org/10.1111/j.1365-2788.1995.tb00912.x
Lowry MA, Sovner R. Severe behavior problems associated with rapid cycling bipolar disorder in two adults with profound mental retardation. J Intellect Disabil Res 1992; 36: 269-81. http://dx.doi.org/10.1111/j.1365-2788.1992.tb00515.x DOI: https://doi.org/10.1111/j.1365-2788.1992.tb00515.x
Khreim I, Mikkelsen E. Anxiety disorders in adults with mental retardation. Psych Annals 1997; 27(3): 175-81. DOI: https://doi.org/10.3928/0048-5713-19970301-09
Silka VR, Hauser MJ. Psychiatric assessment of the person with mental retardation. Psych Annals 1997; 27(3): 162-69. DOI: https://doi.org/10.3928/0048-5713-19970301-07
Ryan R, Sunada K. Medical evaluation of persons with mental retardation referred for psychiatric assessment. General Hospital Psych 1997; 19: 274-80. http://dx.doi.org/10.1016/S0163-8343(97)00023-6 DOI: https://doi.org/10.1016/S0163-8343(97)00023-6
Barron J, Sandman CA. Paradoxical excitement to sedative-hypnotics in mentally retarded clients. Am J Mental Deficiency 1985; 90(2): 124-29.
Stavrakaki C, Mintsioulis G. Implications of a clinical study of anxiety disorders in persons with mental retardation. Psych Annals 1997; 27(3): 182-97. DOI: https://doi.org/10.3928/0048-5713-19970301-10
Kaplan HI, Sadock BJ, eds. Comprehensive Textbook of Psychiatry/V, Baltimore: Williams & Wilkins 1989.
Powers RE. Primary care assessment and management of aggressive behavior toward others for the adult with mental retardation and developmental disabilities. Bureau Geriatric Psych 2005.
Matson JL, Bamburg JW, Mayville EA, et al. Psychopharmacology and mental retardation: a 10 year review (1990 –1999). Res Dev Disabil 2000; (21): 263-96. http://dx.doi.org/10.1016/S0891-4222(00)00042-1 DOI: https://doi.org/10.1016/S0891-4222(00)00042-1
Singh AN, Matson JL, Hill BD, et al. The use of clozapine among individuals with intellectual disability: A review. Res Dev Disabil 2010; (31): 1135-41. http://dx.doi.org/10.1016/j.ridd.2010.07.003 DOI: https://doi.org/10.1016/j.ridd.2010.07.003
Singh AN, Matson JL, Cooper CL, et al. The use of risperidone among individuals with mental retardation: clinically supported or not? Res Dev Disabil 2005; (26): 203-18. http://dx.doi.org/10.1016/j.ridd.2004.07.001 DOI: https://doi.org/10.1016/j.ridd.2004.07.001
Radouco-Thomas M, Bolduc M, Brisson A, et al. Pilot study on the use of psychotropic medication in persons with mental retardation. Progr Neuro-Psychopharmacol Biol Psych 2004; 879-83. http://dx.doi.org/10.1016/j.pnpbp.2004.05.029 DOI: https://doi.org/10.1016/j.pnpbp.2004.05.029
Deb S, Chaplin R, Sohanpal S, et al. The effectiveness of mood stabilizers and antiepileptic medication for the management of behavior problems in adults with intellectual disability: a systematic review. J Intellect Disabil Res 2008; 52(2): 107-13. DOI: https://doi.org/10.1111/j.1365-2788.2007.00965.x
Holden B, Gitlesen JP. Psychotropic medication in adults with mental retardation: prevalence, and prescription practices. Res Dev Disabil 2004; (25): 509-21. http://dx.doi.org/10.1016/j.ridd.2004.03.004 DOI: https://doi.org/10.1016/j.ridd.2004.03.004
Glazer WM. Olanzapine and the new generation of antipsychotic agents: patterns of use. J Clin Psych 1997; 58(Suppl 10): 18-21.
Lott IT, McGregor M, Engelman L, Touchette P, Tournay A, Sandman C, et al. Longitudinal prescribing patterns for psychoactive medications in community-based individuals with developmental disabilities: utilization of pharmacy records. J Intellect Disabil Res 2004; 48(Pt 6): 563-71. http://dx.doi.org/10.1111/j.1365-2788.2004.00625.x DOI: https://doi.org/10.1111/j.1365-2788.2004.00625.x
Spreat S, Conroy JW, Jones JC. Use of psychotropic medication in Oklahoma: a statewide survey. Am J Ment Retard 1997; 102(1): 80-5. http://dx.doi.org/10.1352/0895-8017(1997)102<0080:UOPMIO>2.0.CO;2 DOI: https://doi.org/10.1352/0895-8017(1997)102<0080:UOPMIO>2.0.CO;2
Spreat S, Conroy JW, Fullerton A. Statewide longitudinal survey of psychotropic medication use for persons with mental retardation: 1994 to 2000. Am J Ment Retard 2004; 109(4): 322-31. http://dx.doi.org/10.1352/0895-8017(2004)109<322:SLSOPM>2.0.CO;2 DOI: https://doi.org/10.1352/0895-8017(2004)109<322:SLSOPM>2.0.CO;2
Tyrer P, Oliver-Africano PC, Ahmed Z, et al. Risperidone, haloperidol, and placebo in the treatment of aggressive challenging behaviour in patients with intellectual disability: a randomised controlled trial. Lancet 2008; 371(9606): 57-63. http://dx.doi.org/10.1016/S0140-6736(08)60072-0 DOI: https://doi.org/10.1016/S0140-6736(08)60072-0
Gagiano C, Read S, Thorpe L. Short-and long-term efficacy and safety of risperidone in adults with disruptive behavior disorders. Psychopharmacology (Berl) 2005; 179(3): 629-36. http://dx.doi.org/10.1007/s00213-004-2093-2 DOI: https://doi.org/10.1007/s00213-004-2093-2
Vanden Borre R, Vermote R, Buttiens M, et al: Risperidone as add-on therapy in behavioural disturbances in mental retardation: a double-blind placebo-controlled cross-over study. Acta Psychiatr Scand 1993; 87: 167-71. http://dx.doi.org/10.1111/j.1600-0447.1993.tb03350.x DOI: https://doi.org/10.1111/j.1600-0447.1993.tb03350.x
Amore M, Bertelli M, Villani D, Tamborini S, Rossi M. Olanzapine vs. risperidone in treating aggressive behaviours in adults with intellectual disability: a single blind study. J Intellect Disabil Res 2011; 55(2): 210-18. http://dx.doi.org/10.1111/j.1365-2788.2010.01352.x DOI: https://doi.org/10.1111/j.1365-2788.2010.01352.x
Hammock R, Levine WR, Schroeder SR. Brief Report. Effects of Clozapine on Self-Injurious Behavior of Two Risperidone Nonresponders with Mental Retardation. J Autism Dev Disord 2001; 31(1): 109-13. http://dx.doi.org/10.1023/A:1005626100084 DOI: https://doi.org/10.1023/A:1005626100084
Hammock RG, Schroeder SR, Levine WR. The effect of clozapine on self-injurious behavior. J Autism Dev Disord 1995; 25: 611-26. http://dx.doi.org/10.1007/BF02178191 DOI: https://doi.org/10.1007/BF02178191
Craft M, Ismail IA, Krishnamurti D, et al. Lithium in the treatment of aggression in mentally handicapped patients: a double-blind trial. Br J Psych 1987; 150: 685-89. http://dx.doi.org/10.1192/bjp.150.5.685 DOI: https://doi.org/10.1192/bjp.150.5.685
Tyrer SP, Walsh A, Edwards DE, et al. Factors associated with a good response to lithium in aggressive mentally handicapped subjects. Progr Neuro-Psychopharmacol Biol Psych 1984; 8(4-6): 751-55. DOI: https://doi.org/10.1016/0278-5846(84)90052-6
Reid AH, Naylor GJ, Kay DSG. A double-blind, placebo-controlled, crossover trial of carbamazepine in overactive severely mentally handicapped patients. Psychol Med 1981; 11: 109-13. http://dx.doi.org/10.1017/S0033291700053320 DOI: https://doi.org/10.1017/S0033291700053320
Lewis MH, Bodfish JW. Clomipramine treatment for self-injurious behavior of individuals with mental retardation: a double-blind comparison with placebo. Am J Mental Retardation 1996; 100(6): 654-55.
Cohen S, Ihrig K, Lott RS, Kerrick JM. Risperidone for Aggression and Self-Injurious Behavior in Adults with Mental Retardation. J Autism Dev Disord 1998; 28(3): 229-33. http://dx.doi.org/10.1023/A:1026069421988 DOI: https://doi.org/10.1023/A:1026069421988
Durst R, Rubin-Jabotinsky K, Raskin S, Katz G, Zislin J. Risperidone in treating behavioural disturbances of Prader-Willi syndrome. Acta Psychiatr Scand 2000; 102: 461-65. http://dx.doi.org/10.1034/j.1600-0447.2000.102006461.x DOI: https://doi.org/10.1034/j.1600-0447.2000.102006461.x
Lott RS, Kerrick MJ, Cohen SA. Clinical and economic aspects of risperidone treatment in adults with mental retardation and behavioral disturbance. Psychopharmacol Bull 1996; 32: 721-29.
Khan BU. Brief report: risperidone for severely disturbed behavior and tardive dyskinesia in developmentally disabled adults. J Autism Dev Disord 1997; 27: 479-89. http://dx.doi.org/10.1023/A:1025813607005 DOI: https://doi.org/10.1023/A:1025813607005
Simon E, Blubaugh KM, Pippidis M. Substituting traditional antipsychotics with risperidone for individuals with mental retardation. Ment Retard 1996; 34: 359-66.
Verhoeven WM. Brief Report: Cyclothymia or Unstable Mood Disorder? A Systematic Treatment Evaluation with Valproic Acid. J Neural Transm 2001; 108(6): 617-27. http://dx.doi.org/10.1007/s007020170039 DOI: https://doi.org/10.1007/s007020170039
Bodfish JW, Madison JT. Diagnosis and fluoxetine treatment of compulsive behavior disorder of adults with mental retardation. Am J Ment Retard 1993; 98(3): 360-7.
Troisi A, Vicario E, Nuccetelli F, Ciani N, Pasini A. Effects of fluoxetine on aggressive behavior of adult inpatients with mental retardation and epilepsy. Pharmacopsychiatry 1995; 28(3): 73-6. http://dx.doi.org/10.1055/s-2007-979593 DOI: https://doi.org/10.1055/s-2007-979593
Davanzo PA, Belin TR, Widawski MH, King BH. Paroxetine treatment of aggression and self-injury in persons with mental retardation. Am J Ment Retard 1998; 102(5): 427-37. http://dx.doi.org/10.1352/0895-8017(1998)102<0427:PTOAAS>2.0.CO;2 DOI: https://doi.org/10.1352/0895-8017(1998)102<0427:PTOAAS>2.0.CO;2
La Malfa G, Bertelli M, Conte M. Fluvoxamine and aggression in mental retardation. Psychiatr Serv 2001; 52(8): 1105. http://dx.doi.org/10.1176/appi.ps.52.8.1105 DOI: https://doi.org/10.1176/appi.ps.52.8.1105
Natarajan D, Martin AJ, Tesh D. Risperidone therapy in the control of behavioural disturbances in patients with learning disability. Ir J Psychol Med 1997; 14: 69-71. DOI: https://doi.org/10.1017/S0790966700003050
Ruedrich SL, Swales TP, Rossvanes C, Diana L, Arkadiev V, Lim K. Atypical antipsychotic medication improves aggression, but not self-injurious behaviour, in adults with intellectual disabilities. J Intellect Disabil Res 2008; 52(Pt 2): 132-40. DOI: https://doi.org/10.1111/j.1365-2788.2007.00981.x
Cohen S, Fitzgerald B, Okos A, et al. Weight, lipids, glucose, and behavioral measures with ziprasidone treatment in a population with mental retardation. J Clin Psychiatry 2003; 64(1): 60-2. http://dx.doi.org/10.4088/JCP.v64n0112 DOI: https://doi.org/10.4088/JCP.v64n0112
Buzan RD, Dubovsky SL, Firestone D, et al. Use of clozapine in 10 mentally retarded adults. J Neuropsychiatry 1998; 10: 93-95. DOI: https://doi.org/10.1176/jnp.10.1.93
Thalayasingam S, Alexander RT, Singh I. The use of clozapine in adults with intellectual disability. J Intellect Disabil Res 2004; 48(Pt 6): 572-9. http://dx.doi.org/10.1111/j.1365-2788.2004.00626.x DOI: https://doi.org/10.1111/j.1365-2788.2004.00626.x
Janowsky DS, Barnhill J, Davis JM. Olanzapine for Self Injurious, Aggressive, and Disruptive Behaviors in Intellectually Disabled Adults: A Retrospective, Open Label, Naturalistic Trial. J Clin Psychiatry 2003; 64: 1258-65. http://dx.doi.org/10.4088/JCP.v64n1018 DOI: https://doi.org/10.4088/JCP.v64n1018
Ruedrich S, Swales TP, Fossaceca C, et al. Effect of divalproex sodium on aggression and self-injurious behaviour in adults with intellectual disability: a retrospective review. J Intellect Disabil Res 1999; 43: 105-11. http://dx.doi.org/10.1046/j.1365-2788.1999.00193.x DOI: https://doi.org/10.1046/j.1365-2788.1999.00193.x
Janowsky DS, Kraus JE, Barnhill J, Elamir B, Davis JM. Effects of topiramate on aggressive, self-injurious, and disruptive/destructive behaviors in the intellectually disabled: an open-label retrospective study. J Clin Psychopharmacol 2003; 23(5): 500-4. http://dx.doi.org/10.1097/01.jcp.0000088906.24613.76 DOI: https://doi.org/10.1097/01.jcp.0000088906.24613.76
Dale PG. Lithium therapy in aggressive mentally subnormal patients. Br J Psychiatry 1980; 137: 469-74. http://dx.doi.org/10.1192/bjp.137.5.469 DOI: https://doi.org/10.1192/bjp.137.5.469
Spreat S, Behar D, Reneski B, Miazzo P. Lithium carbonate for aggression in mentally retarded persons. Compr Psychiatry 1989; 30(6): 505-11. http://dx.doi.org/10.1016/0010-440X(89)90080-1 DOI: https://doi.org/10.1016/0010-440X(89)90080-1
Langee HR. Retrospective study of lithium use for institutionalized mentally retarded individuals with behavior disorders. Am J Mental Retardation 1990; 94: 448-52.
Janowsky DS, Shetty M, Barnhill J, Elamir B, Davis JM. Serotonergic antidepressant effects on aggressive, self-injurious and destructive/disruptive behaviours in intellectually disabled adults: a retrospective, open-label, naturalistic trial. Int J Neuropsychopharmacol 2005; 8(1): 37-48. http://dx.doi.org/10.1017/S146114570400481X DOI: https://doi.org/10.1017/S146114570400481X
Branford D, Baumik S. Selective serotonin re-uptake inhibitors for the treatment of perseverative and maladaptive behaviours of people with intellectual disability. J Intellect Disabil Res 1998; 42(4): 301-6. http://dx.doi.org/10.1046/j.1365-2788.1998.00144.x DOI: https://doi.org/10.1046/j.1365-2788.1998.00144.x
Brahm NC, Farmer KC, Brown RC. Risperidone for the treatment of fecal smearing in a developmentally disabled adult. Am J Health Syst Pharm 2007; 64(4): 382-4. http://dx.doi.org/10.2146/ajhp060176 DOI: https://doi.org/10.2146/ajhp060176
Kamal M, Kerry M. The use of clozapine in an individual with moderate intellectualdisability, aggressive behavior and resistant psychosis. Ir J Med Psych 1999; 16(1): 32-33. DOI: https://doi.org/10.1017/S0790966700005024
Goetzl U, Grunberg F, Berkowitz B. Lithium carbonate in the management of hyperactive aggressive behavior of the mentally retarded. Compr Psychiatry 1977; 18(6): 599-606. http://dx.doi.org/10.1016/S0010-440X(97)90013-4 DOI: https://doi.org/10.1016/S0010-440X(97)90013-4
Sovner R, Hurley A. The management of chronic behavior disorders in mentally retarded adults with lithium carbonate. J Nerv Ment Dis 1981; 169(3): 191-5. http://dx.doi.org/10.1097/00005053-198103000-00007 DOI: https://doi.org/10.1097/00005053-198103000-00007
Mattes JA. Valproic acid for nonaffective aggression in the mentally retarded. J Nerv Ment Dis 1992; 180(9): 601-2. http://dx.doi.org/10.1097/00005053-199209000-00013 DOI: https://doi.org/10.1097/00005053-199209000-00013
Luiselli JK, Blew P, Thibadeau S. Therapeutic effects and long-term efficacy of antidepressant medication for persons with developmental disabilities. Behavioral assessment in two cases of treatment-resistant aggression and self-injury. Behav Modif 2001; 25(1): 62-78. http://dx.doi.org/10.1177/0145445501251004 DOI: https://doi.org/10.1177/0145445501251004
Gedye A. Serotonergic treatment for aggression in a Down's syndrome adult showing signs of Alzheimer's disease. J Ment Defic Res 1991; 35(3): 247-58. DOI: https://doi.org/10.1111/j.1365-2788.1991.tb01058.x
O'Neil M, Page N, Adkins WN, Eichelman B. Tryptophan-trazodone treatment of aggressive behaviour. Lancet 1986; 2(8511): 859-60. http://dx.doi.org/10.1016/S0140-6736(86)92890-4 DOI: https://doi.org/10.1016/S0140-6736(86)92890-4
Antonacci DJ, Manuel C, Davis E. Diagnosis and treatment of aggression in individuals with developmental disabilities. Psychiatr Q 2008; 79(3): 225-47. http://dx.doi.org/10.1007/s11126-008-9080-4 DOI: https://doi.org/10.1007/s11126-008-9080-4
Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic 1985; 89(5): 485-91. DOI: https://doi.org/10.1037/t10453-000
Rojahn J, Matson JL, Lott D, Esbensen AJ, Smalls Y. The Behavior Problems Inventory: an instrument for the assessment of self-injury, stereotyped behavior, and aggression/destruction in individuals with developmental disabilities. J Autism Dev Disord 2001; 31(6): 577-88. http://dx.doi.org/10.1023/A:1013299028321 DOI: https://doi.org/10.1023/A:1013299028321
Yudofsky SC, Silver JM, Jackson W, Endicott J, Williams D. The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psych 1986; 143(1): 35-39. DOI: https://doi.org/10.1176/ajp.143.1.35
Guy W. ECDEU assessment manual for psycho pharmacology. Rev. Rockville, MD: U.S. National Institute of Health. Psycho-Pharmacol Res Branch 1976; 218-22. DOI: https://doi.org/10.1037/e591322011-001