The purpose of the present study was to examine the experimental and epidemiologic evidence linking benzodiazepine use to driving impairment. We searched MEDLINE, PsycINFO, the Cochrane Collaboration, and EMBASE using the key terms ("benzodiazepines" OR "exp benzodiazepines") AND ("automobile driving" OR "accidents, traffic" OR "driving" OR "driver$") and limited the results to English citations from 1966 to August 5, 2005, with auto-updates for MEDLINE and PsycINFO to November 30, 2007. Experimental studies using driving simulators and on-road tests were sought, as were epidemiologic studies of a case-control or cohort design. Data were extracted by blinded raters and pooled using random-effects models. We excluded studies without control groups or without measures of driving or collisions. Studies with driving measures that could not be combined were also excluded. Of 405 potential articles, 11 epidemiologic and 16 experimental studies were included in the meta-analysis. Associations between motor vehicle collisions (MVCs) and benzodiazepine use were found among 6 case-control studies (OR = 1.61, 95% CI = 1.21 to 2.13, p <.001), and 3 cohort studies (OR = 1.60, 95% CI = 1.29 to 1.97, p <.0001). Only 10 of 97 experimental driving variables could be pooled for analysis. While no consistent findings were observed in studies using driving simulators, increased deviation of lateral position was found on on-road driving tests (standardized mean difference = 0.80, 95% CI = 0.35 to 1.25, p = .0004). Benzodiazepine users were found to be at a significantly increased risk of MVCs compared to nonusers, and these differences may be accounted for by a difficulty in maintaining road position.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti—depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of ≤7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.