Ineffective use of antipsychotic drugs

Doctors are being warned not to “routinely give people with learning disabilities antipsychotic drugs to curb aggressive behaviour”, BBC News reported today. They report that this warning is based on a study in people with learning difficulties, which found that antipsychotics were no more successful than a dummy pill for reducing aggression. In fact, the dummy pill was more effective.

The reports are based on results from a well-conducted trial in 86 people with learning difficulties who had recently shown aggressive behaviour. The researchers wanted to examine whether antipsychotics were different to placebo for controlling aggression in people with intellectual disabilities, as the evidence supporting this common practice was not considered to be convincing.

The findings of this study do suggest that antipsychotics may be no better than placebo. When using any treatments doctors need to consider the balance of benefits and harms that these drugs may have. This study adds weight to the argument that for people with aggressive behaviour and intellectual disabilities but not psychoses, the benefits of antipsychotics may not balance out potential harm.

Where did the story come from?

Prof. Peter Tyrer and colleagues from Imperial College London, and nine other UK universities and hospitals, and one hospital in Australia carried out the research. The study was funded by the UK National Coordinating Centre for Health Technology Assessment. The study was published in the peer-reviewed medical journal: The Lancet.

What kind of scientific study was this?

This was a double blind randomised controlled trial, that looked at the effects of antipsychotics on aggressive behaviour in people with intellectual disabilities.

Between 2002 and 2006, the researchers enrolled 86 adults (aged 26 to 55) who had intellectual disabilities (an IQ of less than 75) and at least two recent episodes of aggressive behaviour, but who did not have psychoses. People who had received an injection of antipsychotic drugs in the past three months or oral antipsychotic drugs over the past week, or people who had been sectioned, were not included.

The participants were randomly assigned to haloperidol, risperidone, or placebo by independent researchers. All drugs were given as tablets. Participants were asked to take the drugs for 12 weeks, and could continue to take the drugs for up to 26 weeks if patient and clinician preferred it. Doctors could adjust the doses as needed. The main outcome that the researchers were interested in was a change in aggression from the beginning of the study to four weeks into the study, and this was measured using a standard scale (the modified overt aggression scale). Participants were also assessed for behaviour and quality of life using standard scales at four, 12, and 24 weeks. The effect on their carers was also assessed.

What were the results of the study?

Over 90% of patients took most (80% or more) of their assigned medication. The researchers found that although there was a reduction in aggression scores in all three groups by four weeks, it decreased most in the placebo group. However, this difference was not large enough to be statistically significant.

At none of the assessment times was aggression whilst taking placebo significantly worse than with the two antipsychotic drugs. After 26 weeks, the reduction in aggression score was slightly greater with the antipsychotics than with placebo, but again these differences were not large enough to be significant.

There were no significant differences between the groups in behaviour, quality of life, caregiver burden, or side effects. Two people taking haloperidol had to stop taking it because of side effects, as did one patient taking risperidone.

What interpretations did the researchers draw from these results?

The researchers concluded that antipsychotics should no longer be routinely used for treating aggressive behaviour in people with intellectual disabilities.

What does the NHS Knowledge Service make of this study?

This was a well-conducted study, whose results call into question the use of antipsychotics to treat aggression in people with intellectual disabilities. The authors acknowledge some limitations of the study including:

• The authors were unable to recruit as many patients as they wanted to, and the small size of the study means that it may not have been able to detect smaller differences between groups.
• The authors note that other studies that used larger doses of risperidone showed improvements in aberrant behaviour compared to placebo. It is not clear why these results were different, but it may be due to the doses used (although the authors felt that the differences in results were too great to be accounted for by dose). The authors felt that their methods accurately represented ordinary practice, by including a wide range of participants and allowing doctors to adjust the doses of the drugs as they felt necessary. The lower doses used in this study reflected the concerns of the doctors involved that these drugs may have greater side effects in people with intellectual disabilities.
• The comment accompanying the paper in The Lancet suggests that the scale used to measure aggression may not have been adequate to detect changes in aggression in the mixed population included in the study.
• These results apply specifically to adults with aggressive behaviour but not psychoses, and in fact, most of them did not have any psychiatric diagnosis. The results in this population do not necessarily reflect the possible benefits for people with intellectual disability and psychoses or other psychiatric diagnoses.
• The study only investigated people from the community and not those who were hospitalised; for whom aggression may be more severe and findings may have been slightly different.

This study does not provide many clear answers. Doctors need to use their own clinical judgement to consider whether oral anti-psychotic drugs in people whose aggression is currently manageable may be better than waiting until a mental health emergency to start treatment.

When using any treatments, doctors need to consider the balance of benefits and harms that these drugs may have. This study adds weight to the argument that in people with aggressive behaviour and intellectual disabilities but no psychosis, the benefits of antipsychotics may not balance out their potential harms.