Mattes 2005.

Methods	Design: placebo‐controlled parallel trial
Participants	Participants: adults meeting Coccaro‐revised criteria for intermittent explosive disorder (see note 1) Sex: mixed (39 men; 9 women) Age: mean 41.7 (SD 8.8) years Unit of allocation: individual participant Number randomised: 48 Number completing: 24 completed 10 weeks; 45 completed 4 weeks Setting: outpatient; USA Inclusion criteria: aged 18 to 65 years; in generally good health; practicing effective contraception (women of childbearing potential); meeting Coccaro‐revised criteria for intermittent explosive disorder: recurrent incidents of aggression manifest as verbal or physical aggression towards other people, animals or property occurring twice weekly on average for 1 month the degree of aggressiveness expressed is grossly out of proportion to the provocation or any precipitating psychosocial stressors the aggressive behaviour is generally not premeditated (e.g. is impulsive) and is not committed to achieve some tangible objective (e.g. money, power, intimidation etc) the aggressive behaviour causes either marked distress in the individual or impairment in occupational or interpersonal functioning the aggressive behaviour is not better accounted for by another mental disorder, a general medical condition, or the direct physiological effects of a substance Exclusion criteria: schizophrenia; bipolar disorder; epilepsy; dementia; mental retardation; substance abuse in last 6 months; need for treatment with antipsychotics, anticonvulsants or mood stabilisers, or any recent change (within 3 months) in psychotropic medication; significant risk of severely injuring others or self; any current psychiatric or neurological conditions which required specific treatment Ethnicity: not reported Baseline characteristics: mean 13.5 years of education; married (n = 36); physically abused as a child (n = 14); history of ‘road rage’ (n = 38); arrested previously (n = 13); previously in jail because of aggressiveness (n = 7); restraining orders instituted against them (n = 6); prior psychiatric treatment (n = 34); prior psychiatric hospitalisation (n = 6); attempted suicide (n = 4), experience of military combat (n = 4); history of perinatal trauma (n = 4); taking other psychotropic medication (n = 3, all on SSRIs) Age aggressiveness began: in childhood (n = 26), at puberty (n = 9), in adulthood (n = 13). In family history (first‐degree relatives), impulsive aggression (n = 32), depression (n = 15), alcoholism (n = 10). Four diagnoses occurred frequently enough (at least 10 participants) to warrant analysis: ADHD (n = 15), prior alcohol or drug abuse (n = 15), prior major depression (n = 13), and intermittent explosive disorder by DSM‐IV criteria (n = 10). No participants had antisocial or borderline PD, nor a neurological condition that seemed related to aggressiveness.
Interventions	Two conditions: oxcarbazepine / placebo oxcarbazepine (n = 24 randomised); average 1500 (SD 630) mg/day; average of 7.6 weeks on double‐blind medication placebo (n = 24 randomised); average of 7.1 weeks on double‐blind medication Duration of intervention: 10 weeks Length of follow up: participants were not followed up beyond the end of the intervention period Dose adjustment: initial dose oxcarbazepine 150 mg (evening) increased by 150 to 300 mg/day (given in 2 divided doses) after 2 to 4 days on each dose, to at least 1200 mg/day (if tolerated), with a maximum of 2400 mg/day by day 25 if needed. Dose could be administered more slowly, and more could be given at bedtime, if adverse events (assessed by psychiatrist).
Outcomes	Primary outcomes Aggression (self‐reported): OAS‐M (revised; see note 2) Secondary outcomes Hostility: BPRS hostility rating Non‐compliance: proportion of participants discontinuing treatment Other outcomes Patient‐rated global improvement; BPRS total score
Notes	1. All participants met the Coccaro‐revised criteria for intermittent explosive, although only 10 of the 48 randomised met DSM‐IV criteria for intermittent explosive disorder  2. OAS‐M was “slightly revised” by the trial investigators, to “improve face validity and limit variability and skewness”
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Information obtained from lead author indicated that sequence generation was achieved by the throwing of a dice
Allocation concealment?	Low risk	Further details provided by lead author indicated that concealment achieved by use of, effectively, central allocation by a person not otherwise involved in the study, so that participants and any investigator enrolling participants could not foresee assignment
Blinding? of participants	Low risk	Information provided by lead author indicated that this was a double‐blind study. Appropriate care appears to have been taken to ensure blinding of participants.
Blinding? of personnel	Low risk	Information provided by lead author indicated that this was a double‐blind study. Appropriate care appears to have been taken to ensure blinding of personnel.
Blinding? of outcome assessors	Low risk	Information provided by lead author indicated that this was a double‐blind study. Appropriate care appears to have been taken to ensure blinding of outcome assessors.
Incomplete outcome data addressed? All outcomes	Unclear risk	At completion of intervention (10 weeks): 10/24 missing from intervention (oxcarbazepine) group (6 due to adverse events, 4 due to lack of effectiveness); 14/24 missing from control (placebo) group (3 due to adverse events, 11 due to lack of effectiveness). Unclear whether reason for missing outcome data likely to be related to true outcome. However, trial investigators provide an intention‐to‐treat analysis. In this review, data from 48 participants were included in the analysis.
Free of selective reporting?	Low risk	Study protocol is not available but it seems clear that the published report includes all expected outcomes, including those that were pre‐specified
Free of other bias?	Unclear risk	Several small revisions to the OAS‐M instrument are described and justified, but it is unclear whether the revised scale has been formally tested for validity and reliability. In addition, the investigator states that funding was “provided by Novartis Pharmaceuticals Group” (p.579, col 1) who are the manufacturers of Trileptal, the proprietary name for oxcarbazepine. “Novartis also provided oxcarbazepine tablets and matching placebo” (p.579, col 2). However, the trial is described as “an investigator‐initiated study” and the report clearly states that “this manuscript was written without assistance from Novartis” (p.579, col 1). In addition, the authors describe small revisions to the OAS‐M. The study appeared to be free of other sources of bias.