Is risperidone effective in reducing challenging behaviours in individuals with intellectual disabilities after 1 year or longer use? A placebo‐controlled, randomised, double‐blind discontinuation study

Abstract

Background Many people with intellectual disabilities use risperidone long term for the management of challenging behaviours, despite its limited proof of effectiveness and its clear association with adverse events. Therefore, this study aimed to investigate the effectiveness of ongoing treatment with risperidone in reducing challenging behaviours versus controlled discontinuation on behaviour and health parameters. Method This was a placebo‐controlled, double‐blind, randomised discontinuation trial of risperidone. In the discontinuation group, risperidone was gradually replaced by a placebo over 14 weeks, while the control group maintained their existing dosage. Eight weeks after discontinuation, behaviour (as measured by the ‘Aberrant Behavior Checklist’) and health parameters (dyskinesia, akathisia, parkinsonism, weight, waist circumference, sedation and laboratory outcomes) were compared in both groups. Results A total of 25 participants were included in the trial, of which 11 were randomised into the discontinuation group and 14 were randomised into the continued treatment group. In the discontinuation group, 82% completely withdrew from risperidone. There was no significant change in irritability, compared with the continuation group, although there was a Group*Time effects on stereotypical behaviour in favour of the continuation group. Significant Group*Time effects were also found for weight, waist, body mass index, prolactin levels and testosterone levels, with beneficial effects for the discontinuation group. Conclusion Discontinuation of long‐term risperidone for reducing challenging behaviours is possible, without an increase in irritability. Discontinuation of risperidone may have beneficial effects on weight, waist circumference, prolactin levels and testosterone levels. The study suffered from difficulties in achieving the required sample size, which affected study power and generalizability.

Changes in Health‐Related Quality of Life in People With Intellectual Disabilities Who Discontinue Long‐Term Used Antipsychotic Drugs for Challenging Behaviors

“…This increase in physical well‐being may be related to the attenuation of side effects, for example, parkinsonism. This beneficial effect of discontinuation adds to the findings of previous studies that showed favorable effects of discontinuation on weight, body mass index, waist circumference, and prolactin and testosterone levels …”

“…This beneficial effect of discontinuation adds to the findings of previous studies that showed favorable effects of discontinuation on weight, body mass index, waist circumference, and prolactin and testosterone levels. [20][21][22] Full or attempted discontinuation led to a decline in mental well-being, which subsequently recovered. The initial worsening may be a direct consequence of withdrawing the therapeutic effect of the antipsychotic medication.…”

“…In this study, data from 2 different discontinuation trials were combined, an open‐label discontinuation trial (registered in The Netherlands National Trial Register: NTR5519) and a double‐blind placebo‐controlled discontinuation trial (registered in The Netherlands National Trial Register: NTR5509). For the current study all data at baseline, 16 weeks (2 weeks after scheduled discontinuation), and 40 weeks (follow‐up, ie, 40 weeks after baseline) were used from the open‐label trial and from the discontinuation group of the double‐blind trial.…”

Optimising psychotropic medication prescribing to reduce adverse drug events

“…In this issue, Ramerman et al . () consider whether risperidone remained effective in managing challenging behaviours in individuals with intellectual disabilities after longer‐term use, defined as more than 1 year, by means of a placebo‐controlled, randomised, double‐blind discontinuation study. They found that irritability did not increase in the withdrawal group ( n = 11), with beneficial effects on weight, waist, body mass index and prolactin levels, while those who remained on medication ( n = 14) had lower rates of stereotypical behaviour.…”

“…There are currently ongoing efforts in several countries to reduce inappropriate prescribing in vulnerable populations such as adults and children with ID, but many individuals continue to be treated with psychotropic medication for unclear or offlicence indications. In this issue, Ramerman et al (2019) consider whether risperidone remained effective in managing challenging behaviours in individuals with intellectual disabilities after longer-term use, defined as more than 1 year, by means of a placebo-controlled, randomised, double-blind discontinuation study. They found that irritability did not increase in the withdrawal group (n = 11), with beneficial effects on weight, waist, body mass index and prolactin levels, while those who remained on medication (n = 14) had lower rates of stereotypical behaviour.…”