Bleiberg 1993

Double‐blind, placebo‐controlled single‐patient study of dextroamphetamine (and other agents) on attentional function after TBI.

Evans 1987

Randomised, multiple‐block, single‐patient study of methylphenidate and dextroamphetamine on attentional function in a single young male adult survivor of TBI.

Green 2004

Retrospective, case‐controlled study to determine effectiveness and tolerability of Amantadine. Significant improvement in amantadine group for Ranchos Los Amigos level. Amantadine was well tolerated.

Gualtieri 1988

Double‐blind, placebo controlled cross‐over study of effects of two doses of methylphenidate on attentional function after TBI.

Hornstein 1996

Retrospectively looked at 27 patients who had been admitted to the head injury rehab unit and had been prescribed dextroamphetamine. Dextroamphetamine enhanced the recovery and functional status in 15 of the 27. The 15 responders showed a significant improvement in GOS following treatment (P = 0.007). The only significant difference between these patients and those that did not respond to dextroamphetamine was duration between the TBI and treatment, with responders being treated more rapidly.

Hornyak 1997

Retrospective uncontrolled study of illustrative case histories.

Kaelin 1996

Multiple baseline, non‐randomised (A‐A‐B‐A) design study of the effect of methylphenidate on measures of attention after TBI. Disability Rating Scale (DRS) changes are also reported. Improvements in DRS are noted both spontaneously during the first seven‐day interval (A‐A) and the second seven‐day interval, during which methylphenidate is administered (A‐B). Friedman two‐way ANOVA by ranks was used to compare average weekly change in DRS score and suggested that the mean improvement in DRS on treatment (27%) approached a significant difference (P < 0.06) from the A‐A change in baseline DRS score (15%).

Mahalick 1998

Study of effects of methylphenidate on attentional function in oriented children after TBI.

Meyers 1998

Non‐randomised, uncontrolled use of methyphenidate in different patient groups (primary malignant gliomas).

Meythaler 2002

Not restricted to severe GCS (<8). Groups by chance not well matched for DRS on entry.

Mooney 1993

Randomised, single‐blind, placebo‐controlled trial of effect of methylphenidate on injury‐related anger following TBI.

Passler 2001

Retrospectively looked at the outcome of five patients who were in a vegetative state following TBI. Bromocriptine treatment was given as part of a comprehensive rehabilitation programme. With the DRS being used as a measurement of outcome, there was a significant improvement in all of the five patients compared to the general prediction of recovery.

Plenger 1996

Administration of 0.6mg/kg/day of methylphenidate (divided into two doses at 8 am and noon) versus placebo in a group of 23 adults (ages 16‐64 years) who had made a partial recovery following a "complicated mild" to "moderately severe" TBI. Partial recovery was defined as a minimum Galveston Orientation and Amnesia Test (GOAT) score of 65 as a criterion of resolution of post‐traumatic amnesia. Primary outcomes were the Disability Rating Scale (DRS) and measures of attention and motor performance at 30 and 90 days. Methylphenidate (or placebo) was discontinued for at least four days before assessment to allow resolution of temporary immediately drug‐related effects. Main outcome endpoint is the Disability Rating Scale (DRS). The maximum score a patient can obtain on the DRS is 29 (extreme vegetative state). A person without disability would score zero. As discussed in the text of the review, the patients in this study were relatively unimpaired at the time of injury. This is reflected in the fact that the DRS score distributions in this study were extremely left‐skewed (in the direction of less disability). Non‐parametric analyses are used in the original paper to claim significant effect on DRS at 30, but not 90 days, in treatment group. Study excluded from review because of marked drop‐out from both treatment and control groups.

Schneider 1999

Cross‐over study (two week treatment phases separated by two week washout) of amantadine up to maximum 150mg/day in TBI (no injury severity threshold). Only 10 of 18 enrolled patients completed study. Neuropsychological and behavioural rating scale endpoints: no statistically significant differences seen.

Speech 1993

Double‐blind, placebo controlled cross‐over study of effects of methylphenidate on attentional endpoints after TBI, plus a social behavioural rating scale. No statistically significant effects seen.

Whyte 1997

Study of short‐term effects of methylphenidate on attentional function in oriented patients after TBI.

Whyte 2004

Randomised, controlled trial of the effects of methyphenidate on attention deficits after TBI.

Williams 1998

Double‐blind, placebo‐controlled, within‐patient cross‐over study of attentional function only in oriented, paediatric TBI survivors (concluding no benefit to use of methyphenidate).