A Randomized Placebo-Controlled Trial of Citalopram for Anxiety Disorders Following Traumatic Brain Injury

Anxiety occurs commonly after traumatic brain injury and may influence cognitive, behavioral, and somatic presentations that may interfere with patients' recovery and adaptation to life after brain injury. TBI involves both diffuse brain injury as well as frequent focal injuries to frontal and temporal structures, including hippocampus and amygdala, areas that are also implicated in the neurobiology of anxiety. Although there are anecdotal reports of the benefits of SRIs in the treatment of anxiety in association with TBI, there are unfortunately no controlled trials to establish SRI efficacy in patients whose anxiety is considered secondary to brain injury.

A randomized placebo controlled clinical trial design will be used to investigate the effectiveness of citalopram in patients with anxiety disorder due to a general medical condition, specifically traumatic brain injury (TBI). Beneficiaries who are between 3 and 24 months post injury and who meet criteria for DSM-IV diagnosis of anxiety disorder due to TBI will be recruited from the 7 DVBIC VA and Military Medical Centers. Participants will be randomized to receive an increasing dose of citalopram or placebo up to a dose of 40 mg of citalopram or 4 pills of placebo over a 12-week treatment period. Patients will receive comprehensive multidisciplinary evaluations at a DVBIC site, including neurology, neuropsychology and psychiatry interviews and evaluations at baseline, 12 weeks and 12 months.

Participants will sign informed consent prior to the administration of research tests and scales. An informational script is read to individuals seen within the protocol timeframe. This script will provide a necessary standardization for the presentation of the protocol to potential participants. It also specifies the research coordinator as the individual to present the protocol, rather than a primary clinical care provider. After the script is read, the individual will be given the informed consent to review.

Patients will not be eligible to participate/consent to participate in the study until they reach a Rancho Los Amigos level of 7 or 8. If there is any question as to a patient's capacity to consent, the neuropsychologist and/or psychiatrist involved in the study will assess the subject's intellectual and mental faculties prior to consent. Any confusional state prohibits a subjects from being rated as a 7 or 8. Additionally, in our experience, most patients are not able to undergo a full evaluation in the Walter Reed DVBIC program until they reach this level of recovery. Therefore, we anticipate that almost all patients evaluated in our program will have the capacity to give informed consent.

After signing the volunteer informed consent, the tests and scales will be administered and patients will be randomized to receive a 12-week course of citalopram or placebo. Female participants of childbearing potential will be given a serum pregnancy test (up to 1 tablespoon) prior to being randomized to the study medication. If the result of this test is positive, she will not be allowed to participate in this study. The study physician will discuss alternative treatment options.