Withdrawing off-label antipsychotics in people with intellectual disabilities: why does it fail?

Antipsychotics are often used off-label in people with intellectual disabilities for challenging behavior (20-45% of the population receiving formal healthcare). There is no evidence for efficacy. However, metabolic and extrapyramidal side effects are very common. Despite dubious efficacy and concerns about safety, full withdrawal cannot be achieved in over 50% of patients (even if behavior does not deteriorate). We postulate 3 mechanisms: (1)effects of subjective interpretation of behavior by caregivers, influenced by fear of worsening behaviour after drug reduction, (2)it cannot be excluded that some patients might benefit from AP treatment, through a direct effect on behavior, improvement of sleep, or because of previously undiagnosed psychiatric illness, (3)withdrawal symptoms may occur, such as agitation, mania, akathisia, and withdrawal dyskinesia. These symptoms may be misinterpreted as recurrence of challenging behaviour. These hypotheses are tested in a double-blinded placebo-controlled study: participants will be divided in a discontinuation group (gradual decline of AP) and a control group (continuing AP dose). Behaviour, sleep, psychiatric disorders and side effects will be measured and compared between groups. If no differences between groups are found regarding changes in behaviour or drop out of study, the first hypothesis will be supported. Study findings will be included in new guidelines replacing current practice-based off-label prescription of AP.

Failure of discontinuation of off-label antipsychotics in people with intellectual disabilities is the result of (1) subjective interpretation of behavior by caregivers, influenced by fear of worsening of behavior after drug reduction, (2) a beneficial effect of AP treatment, through a direct effect on behavior, improvement of sleep, or because of previously undiagnosed psychiatric illness, (3)withdrawal symptoms, such as agitation, mania, akathisia, and withdrawal dyskinesia are misinterpreted as recurrence of behavioral problems.

Dose reduction will start 2 weeks after inclusion. The code will be broken after 22 weeks, patients will be followed open label for 18 weeks (care as usual). The total study duration is 40 weeks. Assessments will be performed at baseline, and 2,4,5,6,8,10,12,16,22,40 weeks after start.

Risperidone or pipamperone
tablets will be replaced by liquid form. All
participants receive a dosage scheme:
-25% of the original dosage every 4 weeks in
the discontinuation group, dosage remains
unaltered in the control group.