Skip to main content Accessibility help

Quetiapine for Mania Due to Traumatic Brain Injury

  • Timothy J. Oster, C. Alan Anderson, Christopher M. Filley, Hal S. Wortzel and David B. Arciniegas...


Secondary mania develops in as many as 9% of persons with traumatic brain injuries.The treatment of posttraumatic mania is not well defined, and agents traditionally used for the treatment of idiopathic manic episodes may not be well suited for use among individuals with traumatic brain injuries. Atypical antipsychotics are indicated for the treatment of idiopathic bipolar disorder, and have been used for other purposes among individuals with posttraumatic neuropsychiatric disturbances. This article offers the first description of the treatment of posttraumatic mania using the atypical antipsychotic quetiapine. Beneficial effects of this agent on posttraumatic mania, cognitive impairments, and functional disability in the subacute post-injury period are described. Possible mechanisms of action are discussed and the need for additional investigation of quetiapine for posttraumatic mania is highlighted.


Corresponding author

Please direct all correspondence to: David B. Arciniegas, MD, Neurobehavioral Disorders Program, University of Colorado School of Medicine, Campus Box C268-25, 4200 East Ninth Avenue, Denver, CO 80262; E-mail:


Hide All
1.Jorge, RE, Robinson, RG, Starkstein, SE, Arndt, SV, Forrester, AW, Geisler, FH. Secondary mania following traumatic brain injury. Am J Psychiatry. 1993;150:916921.
2.van Reekum, R, Cohen, T, Wong, J. Can traumatic brain injury cause psychiatric disorders? J Neuropsychiatry Clin Neurosci. 2000;12:316327.
3.Jorge, R, Robinson, RG. Mood disorders following traumatic brain injury. Int Rev Psychiatry. 2003;15:317327.
4.Warden, DL, Gordon, B, McAllister, TW, et al.Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006;23:14681501.
5.Starkstein, SE, Pearlson, GD, Boston, J, Robinson, RG. Mania after brain injury. A controlled study of causative factors. Arch Neurol. 1987;44:10691073.
6.Stewart, JT, Hemsath, RH. Bipolar illness following traumatic brain injury: treatment with lithium and carbamazepine. J Clin Psychiatry. 1988;49:7475.
7.Bouvy, PF, van de Wetering, BJ, Meerwaldt, JD, Bruijn, JB. A case of organic brain syndrome following head injury sucessfully treated with carbamazepine. Acta Psychiatr Scand. 1988;77:361363.
8.Kim, E, Humaran, TJ. Divalproex in the management of neuropsychiatric complications of remote acquired brain injury. J Neuropsychiatry Clip Neurosci. 2002;14:202205.
9.Pope, HG, McElroy, SL, Satlin, A, Hudson, JI, Keck, PE Jr, Kalish, R. Head injury, bipolar disorder and response to valproate. Compr Psychiatry. 1988;29:3438.
10.Monji, A, Yoshida, I, Koga, H, Tashiro, K, Tashiro, N. Brain injury-induced rapid-cycling affective disorder successfully treated with valproate. Psychosomatics. 1999;40:448449.
11.Yassa, R, Cvejic, J. Valproate in the treatment of posttraumatic bipolar disorder in a psychogeriatric patient. J Geriatr Psychiatry Neurol. 1994;7:5557.
12.Mustafa, B, Evrim, O, Sari, A. Secondary mania following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2005;17:122124.
13.Murai, T, Fujimoto, S. Rapid cycling bipolar disorder after left temporal polar damage. Brain Inj. 2003;17:355358.
14.Arciniegas, DB, Topkoff, J, Silver, JM. Neuropsychiatric aspects of traumatic brain injury. Curr Treat Options Neurol. 2000;2:169186.
15.Arciniegas, DB, Harris, SN, Brousseau, KM. Psychosis following traumatic brain injury. Int Rev Psychiatry. 2003;15:328340.
16.Smith, KR Jr. Goulding, PM, Wilderman, D, Goldfader, PR, Holterman-Hommes, P, Wei, F. Neurobehavioral effects of phenytoin and carbamazepine in patients recovering from brain trauma: a comparative study. Arch Neurol. 1994;51:653660.
17.Hornstein, A, Seliger, G. Cognitive side effects of lithium in closed head injury. J Neuropsychiatry Clin Neurosci. 1989;1:446447.
18.Massagli, TL. Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: implications for use in traumatic brain injury. Arch Phys Med Rehabil. 1991;72:219226.
19.Glenn, MB, Wroblewski, B, Parziale, J, Levine, L, Whyte, J, Rosenthal, M. Lithium carbonate for aggressive behavior or affective instability in ten brain-injured patients. Am J Phys Med Rehabil. 1989;68:221226.
20.Dikmen, SS, Machamer, JE, Winn, HR, Anderson, GD, Temkin, NR. Neuropsychological effects of valproate in traumatic brain injury: a randomized trial. Neurology. 2000;54:895902.
21.Temkin, NR, Dikmen, SS, Anderson, GD, et al.Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. 1999;91:593600.
22.Wilson, MS, Gibson, CJ, Hamm, RJ. Haloperidol, but not olanzapine, impairs cognitive performance after traumatic brain injury in rats. Am J Phys Med Rehabil. 2003;82:871879.
23.Rao, N, Jellinek, HM, Woolston, DC. Agitation in closed head injury: haloperidol effects on rehabilitation outcome. Arch Phys Med Rehabil. 1985;66:3034.
24.Elovic, EP, Lansang, R, Li, Y, Ricker, JH. The use of atypical antipsychotics in traumatic brain injury. J Head Trauma Rehabil. 2003;18:177195.
25.Stanislav, SW. Cognitive effects of antipsychotic agents in persons with traumatic brain injury. Brain Inj. 1997;11:335341.
26.Kline, AE, Massucci, JL, Zafonte, RD, Dixon, CE, Defeo, JR, Rogers, EH. Differential effects of single versus multiple administrations of haloperidol and risperidone on functional outcome after experimental brain trauma. Crit Care Med. 2007;35:919924.
27.Bleiberg, J, Garmoe, W, Cederquist, J. Dexedrine on performance consistency following brain injury: a double-blind placebo crossover case study. Neuropsychiatry Neuropsych Behav Neurol. 1993;6:245248.
28.Perlis, RH, Welge, JA, Vornik, LA, Hirsctifeld, RM, Keck, PE Jr. Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry. 2006;67:509516.
29.Krieger, D, Hansen, K, McDermott, C, et al.Loxapine versus olanzapine in the treatment of delirium following traumatic brain injury. NeuroRehabilitation. 2003;18:205208.
30.Temple, MJ. Use of atypical anti-psychotics in the management of post-traumatic confusional states in traumatic brain injury. J R Army Med Corps. 2003;149:5455.
31.Bennouna, M, Greene, VB, Defranoux, L. Adjuvant galantamine to risperidone improves negative and cognitive symptoms in a patient presenting with schizophrenialike psychosis after traumatic brain injury. J Clin Psychopharmacol. 2005;25:505507.
32.Schreiber, S, Klag, E, Gross, Y, Segman, RH, Pick, CG. Beneficial effect of risperidone on sleep disturbance and psychosis following traumatic brain injury. Int Clin Psychopharmacol. 1998;13:273275.
33.Kim, E, Bijlani, M. A pilot study of quetiapine treatment of aggression due to traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2006;18:547549.
34.Michals, ML, Crismon, ML, Roberts, S, Childs, A. Clozapine response and adverse effects in nine brain-injured patients. J Clin Psychopharmacol. 1993;13:198203.
35.Cole, P, Rabasseda, X. Quetiapine in bipolar disorder: increasing evidence of efficacy and tolerability. Drugs Today (Barc). 2004;40:837852.
36.Serretti, A, De, RD, Lorenzi, C, Berardi, D. New antipsychotics and schizophrenia: a review on efficacy and side effects. Curr Med Chem. 2004;11:343358.
37.Tandon, R, Jibson, MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry. 2002;14:123129.
38.Bilder, RM, Goldman, RS, Volavka, J, et al.Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry. 2002;159:10181028.
39.Harvey, PD. Cognitive and functional effects of atypical antipsychotic medications. J Clin Psychiatry. 2006;67:e13.
40.Harvey, PD, Bowie, CR, Loebel, A. Neuropsychological normalization with long-term atypical antipsychotic treatment: results of a six-month randomized, double-blind comparison of ziprasidone vs. olanzapine. J Neuropsychiatry Clin Neurosci. 2006;18:5463.
41.Macqueen, G, Young, T. Cognitive effects of atypical antipsychotics: focus on bipolar spectrum disorders. Bipolar Disord. 2003;5:5361.
42.Folstein, MF, Folstein, SE, McHugh, PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189198.
43.Dubois, B, Slachevsky, A, Litvan, I, Pillon, B. The FAB: a Frontal Assessment Battery at bedside. Neurology. 2000;55:16211626.
44.Guide for the Uniform Data Set for Medical Rehabilitation (Including the FIMTM instrument), Version 5.1. Buffalo, NY: State University of New York at Buffalo; 1997.
45.Shukla, S, Cook, BL, Mukherjee, S, Godwin, C, Miller, MG. Mania following head trauma. Am J Psychiatry. 1987;144:9396.
46.Starkstein, SE, Boston, JD, Robinson, RG. Mechanisms of mania after brain injury. 12 case reports and review of the literature. J Nerv Ment Dis. 1988;176:87100.
47.Starkstein, SE, Mayberg, HS, Berthier, ML, et al.Mania after brain injury: neuroradiological and metabolic findings. Ann Neurol. 1990;27:652659.
48.Vieta, E, Goikolea, JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord. 2005;7(suppl):2133.
49.Newman-Tancredi, A, Gavaudan, S, Conte, C, et al.Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998;355:245256.
50.Bymaster, FP, Falcone, JF, Bauzon, D, et al.Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol. 2001;430:341349.
51.Tyson, PJ, Roberts, KH, Mortimer, AM. Are the cognitive effects of atypical antipsychotics influenced by their affinity to 5HT-2A receptors? Int J Neurosci. 2004;114:593611.
52.Yatham, LN, Goldstein, JM, Vieta, E, et al.Atypical antipsychotics in bipolar depression: potential mechanisms of action. J Clin Psychiatry. 2005;66(suppl):4048.
53.Buhot, MC, Martin, S, Segu, L. Role of serotonin in memory impairment. Ann Med. 2000;32:210221.
54.Ichikawa, J, Li, Z, Dai, J, Meltzer, HY. Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1A receptor agonism. Brain Res. 2002;956:349357.
55.Velligan, DI, Prihoda, TJ, Sui, D, Ritch, JL, Maples, N, Miller, AL. The effectiveness of quetiapine versus conventional antipsychotics in improving cognitive and functional outcomes in standard treatment settings. J Clin Psychiatry. 2003;64:524531.
56.Randolph, C. RBANS Manual: Repeatable Battery for the Assessment of Neuropsychological Status. San Antonio, Tex: The Psychological Corporation (Harcourt); 1998.
57.Weickert, TW, Goldberg, TE, Marenco, S, Bigelow, LB, Egan, MF, Weinberger, DR. Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds. Neuropsychopharmacology. 2003;28:14911500.
58.Yumru, M, Savas, HA, Kurt, E, et al.Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord. 2006;98:247252.
59.Schneider, LS, Dagerman, KS, Insel, P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294:19341943.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed