Efficacy of a Triptan in the Treatment of Hostility and Aggression Among Convicts With a Psychiatric Treatment Order

Study Overview
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Brief Summary
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In a double blind randomized clinical trial with cross-over design, treatment using naratriptan will be compared to placebo within a group of 30 convicts with psychiatric disorders such as psychosis or psychopathy with repeated aggressive outbursts resistant to conventional psychopharmacologic and other psychotherapeutic treatment. Hypothesis is that addition of naratriptan to the individual treatment regime reduces aggression -and improves general outcome- as compared to addition of placebo and is well tolerated in this group and under these conditions.

Detailed Description
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EFFICACY OF A TRIPTAN IN THE TREATMENT OF HOSTILITY AND AGGRESSION AMONG CONVICTS WITH A PSYCHIATRIC TREATMENT ORDER Adriano van der Loo*, Dr. Rob van Ojen**, Prof. dr. Frank Koerselman**, Prof. Dr. Henk Nijman*, Prof. Dr. Berend Olivier*** *Forensic Psychiatric Center De Kijvelanden, Poortugaal; **University Medical Center and Rudolf Magnus Institute of Neuroscience Utrecht; ***Department of Pharmacy, Utrecht University Background In a large number of studies, hostility, impulsivity and aggression have been demonstrated to be associated with decreased activity of the serotonergic system (Nelson and Chiavegatto 2001). In rodents a specific role for the serotonin-1b receptor has been reported (Olivier et al. 1995) and it has been shown that specific central serotonin-1b/d agonists such as lipophilic triptans have a specific anti-aggressive effect. To date, no studies have been conducted on treatment of hostility, impulsivity or aggression among humans using a triptan. Goal of the Study Aim is to establish the efficacy of naratriptan, registered for the treatment of migraine, as an anti-aggressive agent in patients with refractory disorders of impulse control due to psychosis or psychopathy. Primary question is whether or not violent behavior and aggressive incidents decrease when naratriptan is administered daily in addition to treatment as usual. Secondary questions are: Does overall prognosis of the underlying condition improve with the intervention? Can responders be differentiated from non-responders in terms of covariants including endocrine factors and polymorphisms in areas in the genome that are involved in serotonergic neurotransmission? Is the triptan well tolerated in this group and in this dose-range? Study Design Population The sample consists of male adult volunteers with a psychiatric disorder who have been convicted and sentenced to undergo psychiatric treatment in Forensic Psychiatric Hospital De Kijvelanden after having committed a violent crime and have in the previous year been involved in violent incidents at least three times in spite of comprehensive psychiatric treatment of the underlying disorder. Intervention /Drug /Dosage In the course of a four-week period either a naratriptan 2.5 mg. tablet or a placebo tablet will be added twice to the daily medication in a double blind randomized fashion. Subsequently, after a two-week washout, patients will cross-over towards the alternative treatment condition for another four-week period. Endpoints Outcome will be measured using the AVL (aggression questionnaire) and the SDAS (social dysfunction and aggression scale) after 2, 4, 6, 8, and 10 weeks of treatment. Change on the CGI (Clinical Global Impression) will be compared to baseline. As usual at the study-site, the SOAS-R (Staff Observation Aggression Scale) will be filled in in case of violent incidents and type, number and duration of restraining interventions will be registered. Also recorded will be symptoms occurring during treatment and number and cause of dropout. Description and Estimate of Risk and Burden for Participants Safety and tolerability of both naratriptan and placebo are very well documented. Incidence and nature of side-effects and interactions has been described to be low and relatively mild, also with frequent (daily) use of naratriptan. Patients at risk for side-effects will be excluded from the study. Drugs will be added to the usual medication of the participants. A questionnaire will be administered and blood will be collected upon inclusion in the study. Data including genotype will be processed anonymously.

Official Title
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Efficacy of a Triptan in the Treatment of Hostility and Aggression Among Convicts With a Psychiatric Treatment Order

Conditions
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Psychotic Disorders, Antisocial Personality Disorder, Impulse Regulation Disorder, Intermittent Explosive Disorder

Intervention / Treatment
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* Drug: naratriptan
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient under psychiatric treatment order for violent crime More than two violent incidents in the year preceding inclusion, of which at least one within the last three months Patient is undergoing psychiatric treatment Informed consent Exclusion Criteria: Unable for informed consent Intolerance for any prescription compound Severe liver failure (Child-Pugh grade c) of renal failure (creatinine clearance < 15 ml/min.) Increased risk of coronary vasospasm: symptoms of vascular disorder (including angina pectoris), history of vascular incidents, severe HBP, ECG-abnormalities in history or at screening prior to inclusion, vascular of cardial souffles. History of vascular incidents, hyperlipidaemia, severe HBP, DM Use of vasoconstrictive agents such as ergotamine derivates including methysergide, or other triptans. Increased risk of serotonergic syndrome: use of irreversible MAO-blocker Age < 18 yr. or > 65 yr.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>four week double blind placebo treatment phase | Drug: placebo<br>* four weeks double blind placebo treatment<br>|
| Active Comparator: naratriptan<br>four week double blind experimental treatment using daily naratriptan tablets | Drug: naratriptan<br>* four weeks double blind experimental treatment using oral naratriptan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of aggressive incidents |  | 10 weeks | 
| aggression scores |  | 10 weeks |