Overcoming the barriers experienced in conducting a medication trial in adults with aggressive challenging behaviour and intellectual disabilities.

BACKGROUND: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. METHOD: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs (risperidone and haloperidol) and placebo. RESULTS: The trial faced significant problems in recruitment. The intent was to recruit 120 patients over 2 years in three centres and to use a validated aggression scale (Modified Overt Aggression Scale) score as the primary outcome. Despite doubling the period of recruitment, only 86 patients were ultimately recruited. CONCLUSIONS: Variation in beliefs over the efficacy of drug treatment, difficulties within multidisciplinary teams and perceived ethical concerns over medication trials in this population all contributed to poor recruitment. Where appropriate to the research question cluster randomised trials represent an ethically and logistically feasible alternative to individually randomised trials.

Neuroleptics in the treatment of aggressive challenging behaviour for people with intellectual disabilities: a randomised controlled trial (NACHBID).

OBJECTIVE(S): To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN: A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING: Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS: Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA: treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS: Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES: Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS: There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS: There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.

The effectiveness of mood stabilizers and antiepileptic medication for the management of behaviour problems in adults with intellectual disability: a systematic review.

BACKGROUND: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. METHOD: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood stabilizers in the management of behaviour problems among adults with ID. Electronic searches of PsycInfo, Medline, Embase and Cinahl databases were conducted, as well as a thorough hand search for relevant literature. We reviewed primary trials relating to adults only that satisfied strict inclusion criteria. RESULTS: One randomized controlled trial (RCT) relating to lithium use and two non-RCTs, one on lithium and the other on carbamazepine, were revealed. In addition, one prospective non-controlled trial on sodium valproate and three retrospective case series studies were discovered, of which one considered the efficacy of lithium, one valproate and one topiramate. CONCLUSIONS: The current evidence lends some support for the use of lithium and some antiepileptic mood stabilizer medication for the management of behaviour problems in adults with ID. However, because most studies reviewed here are riddled with obvious methodological constrains, the findings have to be interpreted with caution.

The effectiveness of antidepressant medication in the management of behaviour problems in adults with intellectual disabilities: a systematic review.

BACKGROUND: A comprehensive systematic review was performed to establish the current evidence base regarding the effectiveness of antidepressant medication for the management of behaviour problems in adults with intellectual disabilities. METHOD: An electronic search of PsycInfo, Embase, Medline and Cinahl databases was conducted spanning the time period 1990 to October 2005 for primary trials. This was supplemented by hand searching and cross-referencing of relevant reviews. Strict scientific methodology requirements were formulated that the studies had to meet in order to merit inclusion in this review. RESULTS: One crossover randomized controlled trial in a small cohort, seven prospective uncontrolled trials and two retrospective studies were yielded in the search. Of these, one explored the effectiveness of the tricyclic antidepressant--clomipramine, and nine considered various selective serotonin reuptake inhibitors (SSRIs). CONCLUSION: Evidence based primarily on a small number of either prospective or retrospective case studies that included a small number of participants and often used non-validated outcome measures for a short period of follow-up, suggests that antidepressants, particularly SSRIs, show improvement of aggression and self-injurious behaviour on average in less than 50% of cases and the rest show either no improvement or deterioration. The effect is most pronounced in the presence of an underlying anxiety or an associated diagnosis of obsessive-compulsive disorder. Most studies have highlighted the concern regarding adverse effects.

The effectiveness of antipsychotic medication in the management of behaviour problems in adults with intellectual disabilities.

BACKGROUND: Psychopharmacological intervention in the management of behaviour problems in adults with intellectual disabilities (ID) has become a common treatment strategy. This has become a cause for concern, given that the evidence for its effectiveness is uncertain and most drugs are not licensed for this use. METHODS: A comprehensive systematic review of empirical research on the effectiveness of antipsychotic medication was conducted. Electronic and manual searches of literature were conducted. Stringent scientific methodology determined those primary trials that were worthy of inclusion. RESULTS: This review revealed one randomized controlled trial (RCT), one controlled, four uncontrolled prospective and three retrospective case series studies in adults. Additionally, two studies in both adults and children--one crossover RCT and one prospective controlled trial--were found. CONCLUSION: Presently, there is RCT-based evidence for risperidone to be effective in both adults and children; however, this treatment carries a certain amount of risk associated with adverse effects. There is also evidence to support the use of other antipsychotics, primarily atypicals, but the evidence is based on noncontrolled case studies. There is currently not enough evidence available to recommend specific medication for specific behaviour problems. Before prescribing medication, clinicians should carry out a thorough assessment of behaviour, including its causes and consequences, and draw up a formulation providing the rationale for the prescribed intervention after considering all medication- and nonmedication-based management options.