Methods	Design: placebo-controlled cross-over trial
Participants	Participants: men with DSM-IV personality disorder and impulsive aggressive behaviour (subgroup with AsPD; see note 1) Sex: male only Age: mean 45.1 (SD 6.8) years (whole sample including non-AsPD participants) Unit of allocation: individual participant Number randomised: 46 in whole sample, 10 with AsPD (see note 1) Number completing: not reported Setting: outpatient; single site; USA (New Orleans) Inclusion criteria: over past 6 months, several discrete participant-identified episodes of failure to resist aggressive impulses resulting in serious assaultative acts or destruction of property; degree of aggressiveness expressed during the episodes was grossly out of proportion to any precipitating psychosocial stressor; at least two such episodes during the month prior to entering the study; score of 8 or higher on the Irritability sub scale of the Buss-Durkee Hostility Inventory; must have identified an individual willing to document any impulsive-aggressive outbursts that occurred during the study Exclusion criteria: female (due to potential teratogenic effects of phenytoin); verbal IQ < 80; diagnosis of a DSM-IV-TR Axis I psychiatric disorder; present use of medication; medical/neurological problems (including seizures); liver enzymes not within normal limits Ethnicity: not reported Baseline characteristics: mean verbal IQ 105.8 (SD 10.7); mean 14.3 (SD 2.4) years education; DSM-IV personality disorder diagnoses for phase one completers: obsessive-compulsive personality disorder (n = 12), AsPD (n = 10), narcissistic personality disorder (n = l)
Interventions	Two conditions: phenytoin / placebo phenytoin; 300 mg/day; as 100 three times daily; mean serum phenytoin levels measured after sixth week = 6.0 (SD 3.3) μg/ml; range 0.8 to 14.8 μg/ml; therapeutic range 10 to 20 μg/ml (number randomised not reported) placebo (number randomised not reported) Duration of intervention: 6 weeks Duration of trial: 16 weeks (cross-over trial; two phases, 2-week placebo baseline period, and 2-week placebo washout period between phases) Length of follow up: participants were not followed up beyond the end of the intervention period Dose adjustment: no details reported
Outcomes	Primary outcomes Aggression (observer-reported): Overt Aggression Scale (OAS) scores Secondary outcomes Anger-hostility: Profile of Mood States anger-hostility subscale scores Other outcomes Psychophysiological recordings (including evoked potentials)
Notes	1. 43% of 23 participants had AsPD (n = 10). Data from this subgroup not reported
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	Investigators report that “subjects were randomly assigned” (p.195, col. 2) suggesting that the order of treatments was randomised in this cross-over trial. Further details obtained from trial investigators (2009 email from M Stanford to J Dennis clarifying trial methods; unreferenced) indicated that sequence generation was achieved by use of computer generated random numbers
Allocation concealment?	Unclear	Insufficient information to allow a judgement to be made. Clarification has been requested from the trial investigators but no further information was available at the time this review was prepared
Blinding? of participants	Yes	Investigators described the study as “double-blind”. Response from trial investigators suggests that appropriate care was taken to ensure blinding of participants
Blinding? of personnel	Yes	Investigators described the study as “double-blind”. Response from trial investigators suggests that appropriate care was taken to ensure blinding of personnel
Blinding? of outcome assessors	Yes	Investigators described the study as “double-blind”. Response from trial investigators suggests that appropriate care was taken to ensure blinding of outcome assessors
Incomplete outcome data addressed? All outcomes	No	Incomplete outcome data arise from participants not completing the study and applies to all measured outcomes. Overall, 17 of 46 were non-completers and a further 6 were excluded giving a 50% missing data rate. Review authors judged risk of bias to be high pending data from the AsPD subgroup becoming available
Free of selective reporting?	Yes	Study protocol is not available but it seems clear that the published report includes all expected outcomes
Free of other bias?	Unclear	The investigators declared their research sponsored by the Dreyfus Health Foundation, which is focused on phenytoin and was established “to study, collect, and disseminate information and sponsor collaborative, clinical, and basic health research on its benefits”. The authors have insufficient information to assess whether this constitutes a risk of bias. The trial investigators reported a two-week placebo washout period between phases in this cross-over trial which will have reduced the possibility of carryover effects and the study appeared to be free of other sources of bias