Antidepressant Pharmacotherapy and the Treatment of Depression in Patients With Severe Traumatic Brain Injury: A Controlled, Prospective Study

Background: Untreated or poorly treated depression in patients who suffer from traumatic brain injury can result in greater functional disability and prolonged or ineffective hospital and rehabilitation stays. Literature available on the pharmacologic treatment of depression after traumatic brain injury is scarce. This study investigated in a controlled and prospective manner the use of desipramine, a tricyclic antidepressant, in a series of patients with severe traumatic brain injury.

Method: Ten patients with severe traumatic brain injury and long-standing depression, as diagnosed by DSM-III-R criteria, were admitted to the study because of the intention to be treated with antidepressants. They were randomly assigned to blindly start on either desipramine treatment (N = 6) or placebo lead-in (N = 4). Patients starting with desipramine stayed on that drug; patients starting with placebo lead-in were blindly crossed over to desipramine after 1 month if there was no significant improvement demonstrated by DSM-III-R criteria. All rating clinicians, physicians, and patients were blind to actual treatment and any ratings data. DSM-III-R evaluations were done monthly. An affect/mood scale was done every 2 weeks.

Results: Of all patients evaluable using the DSM-III-R, 6 (86%) of 7 demonstrated resolution of depression and depressed mood during desipramine treatment. (Three received desipramine throughout the study; 3 others started taking placebo and crossed over to desipramine.) One patient refused evaluation on DSM-III-R throughout; 2 patients, both on desipramine, dropped out because of adverse effects (seizure, mania). In addition, there was statistically significant (p = .001) improvement over time and different rates of improvement over time in the treated and untreated groups for the affect/mood scale data.

Conclusion: Results from this small study, utilizing a blinded, placebo lead-in design appear to (1) demonstrate the clinically significant effectiveness of desipramine in treating long-standing depression in a series of patients with severe traumatic brain injury, as rated with DSM-III-R criteria; (2) show statistically significant improvement on the affect/mood scale data, favoring the treated versus untreated (placebo lead-in) group.