Abstract
To evaluate the effectiveness of Concerta XL in reducing levels of aggression, increasing engagement with educational activities and reducing symptoms of ADHD, in young male offenders with ADHD.
Primary outcome will be the effectiveness of treatment with Concerta XL to reduce levels of aggression, measured as the number of recorded critical incidents (records of disruptive behaviour) in the prison records.
Secondary objectives will be to estimate the effectiveness of treatment with Concerta XL to increase engagement with educational activities; and decrease symptoms of ADHD and emotional dysregulation.
Further analyses will test the mediation hypothesis that changes to symptoms of ADHD and emotional dysregulation mediate reduction in aggressive behaviour and engagement in educational activities.
A 12-week open label pilot study of Concerta XL with dose-escalation to a maximum of 90 mg. Following the initial 12-week trial there will be an open label extension with further titration to an optimal dose for each individual participant, for a period of 6-months.
The primary endpoint will be the number of recorded critical incidents (records of disruptive behaviour) in the prison records in the 3-months prior to the
12-week assessment.
Secondary endpoints will be recorded at the
12-week assessment:
- Ratings of aggressive behaviour by prison and education staffs (Modified Overt Aggression Scale – MOAS).
- Engagement with education activities over previous 3-months (Number of sessions attended, number of reports of disruptive behaviour in educational sessions).
- Symptoms of ADHD (CAARS) and emotional dysregulation (WRAADS).
A total of 100 participants will be recruited into the study.
Males aged between 18 and 30 years who provide fully informed consent and have a clinical and research diagnosis of ADHD following assessment with the DIVA clinical interview for DSM-IV ADHD.
Concerta XL capsules, taken orally, at doses of 18, 36, 54, 72 and 90 mg.
The initial treatment trial (and primary endpoint) is for 12-weeks.
The follow up open label extension will add an additional 6-month period.
Overall this study demonstrated the feasibility of conducting clinical trials of ADHD in young adult prisoners. Clinical effects were observed supporting the need for a definitive clinical trial.
The primary outcome was the total number of adjudications reported by prison officers in the electronic prison records. The effects were d=0.53 using the per protocol analysis but only d=0.29 using the ITT analysis. Here the confidence that such change are accounted for by the study medication is uncertain. Adjudication rates are relatively low and it may be that the prison regime is good at responding to adjudications events once they occur. Taking part in the clinical trial with weekly visits form research staff may further impact in a beneficial way on aggressive or antisocial behaviour. However we did not select on the primary outcome, so adjudications rates could have gone up as well as down. Taking into account the small effect on the primary outcome for the ITT analysis, and the moderate effect in the pp analysis it is clear that no conclusions can be drawn from the analysis here. A larger, placebo controlled trial is required to address this question.
With regard to secondary behavioural outcomes reported by prison and education staff, the same arguments apply as for adjudications. No conclusion can be drawn. Overall thee positive effects on behavioural outcomes (aggression, antisocial behaviour and engagement with education) indicate the need for a larger definitive trial powered and designed to address these questions.
In contrast, the effects on symptoms, particular core ADHD symptoms, but also other domains were substantial, being in the range of d=.5 to 2. For example if we consider the effect in core ADHD symptoms measured using the investigator rated Conners ADHD rating scale. The results of the single arm open label pilot study show a mean decrease of 25.0 points with a standard deviation of 9.1. This suggested a standardised effect size of d=2.75. It could then reasonably be assumed that at least 20% of this effect might be attributed to the effects of MPH since previous meta-analyses show an average effect around d=0.5.
The trial procedures and medication were found to be safe. Titration was to lower doses with no evidence of drug seeking behaviour. Adverse effects were those commonly seen when treating ADHD with methylphenidate. No serious adverse events occurred.
Overall this study demonstrated the feasibility of conducting clinical trials of ADHD in young adult prisoners. Clinical effects were observed supporting the need for a definitive clinical trial. The data presented here was successfully used in an application to the National Institute of health Research (NIHR) for a randomised placebo controlled trial of 200 adult offenders with ADHD, following similar procedures to those used here. The study following on from this starts in June 2016.
Primary outcome will be the effectiveness of treatment with Concerta XL to reduce levels of aggression, measured as the number of recorded critical incidents (records of disruptive behaviour) in the prison records.
Secondary objectives will be to estimate the effectiveness of treatment with Concerta XL to increase engagement with educational activities; and decrease symptoms of ADHD and emotional dysregulation.
Further analyses will test the mediation hypothesis that changes to symptoms of ADHD and emotional dysregulation mediate reduction in aggressive behaviour and engagement in educational activities.
A 12-week open label pilot study of Concerta XL with dose-escalation to a maximum of 90 mg. Following the initial 12-week trial there will be an open label extension with further titration to an optimal dose for each individual participant, for a period of 6-months.
The primary endpoint will be the number of recorded critical incidents (records of disruptive behaviour) in the prison records in the 3-months prior to the
12-week assessment.
Secondary endpoints will be recorded at the
12-week assessment:
- Ratings of aggressive behaviour by prison and education staffs (Modified Overt Aggression Scale – MOAS).
- Engagement with education activities over previous 3-months (Number of sessions attended, number of reports of disruptive behaviour in educational sessions).
- Symptoms of ADHD (CAARS) and emotional dysregulation (WRAADS).
A total of 100 participants will be recruited into the study.
Males aged between 18 and 30 years who provide fully informed consent and have a clinical and research diagnosis of ADHD following assessment with the DIVA clinical interview for DSM-IV ADHD.
Concerta XL capsules, taken orally, at doses of 18, 36, 54, 72 and 90 mg.
The initial treatment trial (and primary endpoint) is for 12-weeks.
The follow up open label extension will add an additional 6-month period.
Overall this study demonstrated the feasibility of conducting clinical trials of ADHD in young adult prisoners. Clinical effects were observed supporting the need for a definitive clinical trial.
The primary outcome was the total number of adjudications reported by prison officers in the electronic prison records. The effects were d=0.53 using the per protocol analysis but only d=0.29 using the ITT analysis. Here the confidence that such change are accounted for by the study medication is uncertain. Adjudication rates are relatively low and it may be that the prison regime is good at responding to adjudications events once they occur. Taking part in the clinical trial with weekly visits form research staff may further impact in a beneficial way on aggressive or antisocial behaviour. However we did not select on the primary outcome, so adjudications rates could have gone up as well as down. Taking into account the small effect on the primary outcome for the ITT analysis, and the moderate effect in the pp analysis it is clear that no conclusions can be drawn from the analysis here. A larger, placebo controlled trial is required to address this question.
With regard to secondary behavioural outcomes reported by prison and education staff, the same arguments apply as for adjudications. No conclusion can be drawn. Overall thee positive effects on behavioural outcomes (aggression, antisocial behaviour and engagement with education) indicate the need for a larger definitive trial powered and designed to address these questions.
In contrast, the effects on symptoms, particular core ADHD symptoms, but also other domains were substantial, being in the range of d=.5 to 2. For example if we consider the effect in core ADHD symptoms measured using the investigator rated Conners ADHD rating scale. The results of the single arm open label pilot study show a mean decrease of 25.0 points with a standard deviation of 9.1. This suggested a standardised effect size of d=2.75. It could then reasonably be assumed that at least 20% of this effect might be attributed to the effects of MPH since previous meta-analyses show an average effect around d=0.5.
The trial procedures and medication were found to be safe. Titration was to lower doses with no evidence of drug seeking behaviour. Adverse effects were those commonly seen when treating ADHD with methylphenidate. No serious adverse events occurred.
Overall this study demonstrated the feasibility of conducting clinical trials of ADHD in young adult prisoners. Clinical effects were observed supporting the need for a definitive clinical trial. The data presented here was successfully used in an application to the National Institute of health Research (NIHR) for a randomised placebo controlled trial of 200 adult offenders with ADHD, following similar procedures to those used here. The study following on from this starts in June 2016.
| Original language | English |
|---|---|
| Type | A Pilot study of Concerta XL in adult offenders with ADHD |
| Number of pages | 95 |
| Publication status | Published - 28 Feb 2016 |