Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

Condition(s) targeted: Traumatic Brain Injury

Intervention: Placebo (Drug); Sertraline (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: University of Iowa

Official(s) and/or principal investigator(s):
Ricardo E. Jorge, MD, Principal Investigator, Affiliation: Department of Psychiatry, UI Hospitals and Clinics

Overall contact:
Stephanie A. Rosazza, BA, Phone: 319-353-5807, Email: stephanie-rosazza@uiowa.edu

The purpose of this study is to examine the efficacy of sertraline to prevent the onset of mood and anxiety disorders during the first six months after traumatic brain injury.

Official title: Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome:

Time to onset of DSM-IV defined mood and anxiety disorders; Total Community Integration Questionnaire scores at baseline, 3, and 6 months; Executive function composite will measure cognitive impairment.

Fractional anisotropy of frontal white matter will measure white matter integrity.

Secondary outcome:

Overt Aggression Scale-Modified total score will quantify the degree of aggressive behavior.

DSM-IV defined Personality change due to TBI (disinhibited, aggressive or combined types).

Iowa Gambling Test score will measure the quality of decision making.

Memory function composite will measure cognitive impairment.

Neuroimaging variables

SFE scores will measure the degree of satisfaction with social functioning at one year follow-up.

Detailed description: Traumatic brain injury (TBI) is a leading cause of death and disability among young adults. Mood disorders are the most frequent psychiatric complication of TBI, and have a large impact on family functioning, interpersonal relationships, and ability to return to work or school. Furthermore, a significant proportion of these disorders will progress to more chronic and treatment refractory forms. In spite of their clinical relevance, mood and anxiety disorders remain largely unrecognized and not adequately treated, contributing to greater disability and decreased participation in the aftermath of TBI.

The goals of this study are to learn more about how people recover from brain injury and to evaluate the effect of sertraline (also known as Zoloft) compared to placebo (an inactive substance) in preventing the occurrence of emotional and behavioral problems—such as depression, lack of motivation, anxiety, irritability or aggressive outbursts—following TBI.

In the study, a group of 104 participants with TBI—recruited immediately after resolution of posttraumatic amnesia—will be randomly assigned to receive six months of double-blind treatment with sertraline or placebo.

This study will determine how these emotional and behavioral problems influence thinking, physical recovery, and return to a productive life six months after brain injury. Researchers will also determine if certain brain changes can predict the occurrence of behavioral problems and if treatment with sertraline can prevent them. Additionally, the researchers will examine the effect of sertraline on frequent post-TBI behavioral disorders such as aggression, impulsivity, poor decision making and apathetic symptoms.

Magnetic resonance imaging (MRI)-based volumetry and diffusion tensor imaging will be used to examine the structural correlates of mood and anxiety disorders and to evaluate them as biological predictors of treatment response and community reintegration. The researchers hypothesize that early preventive treatment with sertraline will reduce mood and behavioral symptoms, prevent the occurrence of structural and functional brain changes associated with the onset of mood disorders, increase access to and participation in rehabilitation programs for TBI, and, consequently, improve psychosocial outcome.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18 years or over.

- Meeting the Center for Disease Control (CDC) criteria for TBI.

- Mild, Moderate, or Severe TBI as categorized by initial Glasgow Coma Scale (GCS)

scores 13 to 15, 9 to 12, or 3 to 8, respectively.

- Complete recovery from Post Traumatic Amnesia (PTA) within 4 weeks of the traumatic

episode.

Exclusion Criteria:

- Penetrating head injuries.

- Clinical or neuro-radiological evidence of associate spinal cord injury.

- Patients with severe comprehension deficits (i. e., those who are not able to complete

part II of the Token Test) that precludes a thorough neuropsychiatric evaluation.

- Presence of DSM-IV defined mood, anxiety or psychotic disorder at the time of

enrollment to the study. However, patients with a history of alcohol abuse or alcohol dependence during the year preceding TBI will be included in the study.

- Patients who were taking antidepressants at the time of TBI or during a six month

period prior to the traumatic event.

- Patients who have failed an adequate previous trial with sertraline or had side

effects that prompted the discontinuation of this medication.

- Pregnant women or women that plan to become pregnant during the period of the study.

- Severe complicating illness such as neoplastic disease or uncompensated heart, renal

or liver failure.

Stephanie A. Rosazza, BA, Phone: 319-353-5807, Email: stephanie-rosazza@uiowa.edu

Department of Psychiatry, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242, United States; Recruiting
Jennifer L. Lassner, Phone: 319-335-2134, Email: Jennifer-lassner@uiowa.edu

Related publications:

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Silver, J.M., R.E. Hales, and S.C. Yudofsky, Psychopharmacology of depression in neurologic disorders. J Clin Psychiatry, 1990. 51 Suppl: p. 33-9.

Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following traumatic brain injury. Arch Gen Psychiatry. 2004 Jan;61(1):42-50.

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Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003 Aug 8;301(5634):805-9.

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Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001 Nov 1;50(9):651-8.

Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, Mathews VP, Kalnin A, Lowe MJ. Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology. 2005 Jul;30(7):1334-44.

Bechara A, Damasio H, Tranel D, Damasio AR. The Iowa Gambling Task and the somatic marker hypothesis: some questions and answers. Trends Cogn Sci. 2005 Apr;9(4):159-62; discussion 162-4. Review.

Huisman TA, Schwamm LH, Schaefer PW, Koroshetz WJ, Shetty-Alva N, Ozsunar Y, Wu O, Sorensen AG. Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. AJNR Am J Neuroradiol. 2004 Mar;25(3):370-6.

Salmond CH, Menon DK, Chatfield DA, Williams GB, Pena A, Sahakian BJ, Pickard JD. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage. 2006 Jan 1;29(1):117-24. Epub 2005 Aug 9.

Jorge R, Robinson RG. Mood disorders following traumatic brain injury. NeuroRehabilitation. 2002;17(4):311-24. Review. No abstract available.

Jorge RE, Robinson RG, Arndt S. Are there symptoms that are specific for depressed mood in patients with traumatic brain injury? J Nerv Ment Dis. 1993 Feb;181(2):91-9.

Jorge RE, Robinson RG, Arndt SV, Forrester AW, Geisler F, Starkstein SE. Comparison between acute- and delayed-onset depression following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1993 Winter;5(1):43-9.

Jorge RE, Robinson RG, Arndt SV, Starkstein SE, Forrester AW, Geisler F. Depression following traumatic brain injury: a 1 year longitudinal study. J Affect Disord. 1993 Apr;27(4):233-43.

Jorge RE, Robinson RG, Starkstein SE, Arndt SV. Depression and anxiety following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1993 Fall;5(4):369-74.

Jorge RE, Robinson RG, Starkstein SE, Arndt SV. Influence of major depression on 1-year outcome in patients with traumatic brain injury. J Neurosurg. 1994 Nov;81(5):726-33.

Jorge RE, Robinson RG, Starkstein SE, Arndt SV, Forrester AW, Geisler FH. Secondary mania following traumatic brain injury. Am J Psychiatry. 1993 Jun;150(6):916-21.

Jorge R, Robinson RG. Mood disorders following traumatic brain injury. Int Rev Psychiatry. 2003 Nov;15(4):317-27. Review.

Jorge RE, Starkstein SE. Pathophysiologic aspects of major depression following traumatic brain injury. J Head Trauma Rehabil. 2005 Nov-Dec;20(6):475-87. Review.

Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):426-34.

Starting date: June 2008
Ending date: April 2013
Last updated: May 20, 2009