Liquid Risperidone in the Treatment of Acute Agitation in Psychiatrically Hospitalized Children
Condition: Agitation
MeSH terms: Psychomotor Agitation
Study type: Interventional
Phase: Phase 4

Summary: 
      The goal of this study is to demonstrate safety and efficacy of liquid risperidone in
      psychiatrically hospitalized children, ages 4-12, who would be put in seclusion or restraint,
      or given an intramuscular injection of diphenhydramine because of their out-of-control
      behavior if not medicated with risperidone. The first part of the study will: 1) develop
      appropriate oral doses of medication to reduce out of control or agitated behavior
      effectively with the fewest side effects, and 2) develop a rating system to measure the
      children's behavior i.e. level of improvement, sedation, and untoward effects.
    

Detailed description: 
      A. Develop an appropriate dose structure for risperidone. Children needing oral medication
      will be initially offered a safe minimal dose (0.015 mg/kg) dose of risperidone (between 0.3
      and 0.6mg for children weighing between 20-40kg). If there is no response, or an inadequate
      response (anything less than "much improved" on the Clinical Global Improvement Scale) after
      30 minutes, the next dose (0.02 mg/kg) will be used if there is another occasion to use a
      medication intervention the following day. Similarly, a medium dose (0.025 mg/kg) dose will
      be used if the lower dose is inadequate. The highest dose is 0.3mg/kg. For a big child (we
      have had children who weigh as much as 55kg this would work out to a maximum dose of 1.6
      mg/dose, well within the dose range administered on a one time, daily basis to children (2 mg
      is the usual maximum, though a daily dose of 3-4 mg is not uncommon). If the child is already
      receiving risperidone, total daily dose will not exceed 0.07mg/kg/day (the maximum dose used
      in the RUPP trial). Weight dose chart follows on the next page. Intervention following the 30
      minutes will depend on clinical judgement. It may include a different medication, open
      seclusion, or room restriction.

      B. Develop a rating instrument for the stages of agitation needing to be rated. It has been
      difficult to operationalize when to intervene, and how to rate improvement. There are
      absolutely no guidelines on this. We have developed a list of behaviors that a nurse rater
      will use to observe the child at 5, 15, 30, 45, 60, 90 and 120 minutes after any intervention
      for an episode of agitation. We will, of course, be specifically interested in these measures
      for children receiving risperidone. (It maybe necessary to videotape some children to develop
      reliability on the measure.) The advantage of using such an instrument will be that the
      children will be very closely observed for both positive and negative effects. However, in
      short term treatment trials, sedation and fatigue were the most common "adverse event",
      followed by increased appetite. Neurologic side effects (tremor, dyskinesia, rigidity,
      akathesia and difficulty swallowing) have been reported in chronic use of this medication in
      adults. In children, in the placebo controlled study, only tremor was marginally more common
      in the risperidone group.

      We anticipate having about 20 children and about 60 episodes of severe agitation over a 9
      month period during which we will be able to find a reasonable dose of risperidone, determine
      its onset and duration of action, and its efficacy in shortening episodes of severe
      agitation.

      INCLUSION AND EXCLUSION CRITERIA All psychiatrically hospitalized children on 12North who are
      unable to take a "time out" because they are agitated and out of control are eligible for
      this study. These are children who ordinarily would be treated either with
      seclusion/restraint or an intra-muscular shot of diphenhydramine (Benadryl). Excluded
      children would be those who have had allergic or "bad" reactions to risperidone in the past,
      and those in whom adequate doses have not produced improvement in behavior. Since liquid
      risperidone is frequently used as an intervention on the unit anyway, being part of this
      study is, in fact providing closer supervision than is usually undertaken. Close supervision
      is not required for safety and we are doing it as part of this project to more precisely
      document onset and offset of medication effect as well as to establish a pattern of symptom
      remission.

      RISKS AND DISCOMFORTS The side effects that most frequently occurred in children treated
      every day for several months with this medication include increased appetite, weight gain,
      feeling tired and drowsy, tremor and dyskinesia. Long term use is most associated with weight
      gain. There is a very small risk of extrapyramidal symptoms (akathesia, dystonia). This is
      usually seen with doses higher than are used in this study, but may occur. Prolactin
      elevation and galactorrhea rarely occur, but also are most associated with long term use.

      BENEFITS Development of a safe and effective treatment for severe agitation in children.
      Development of a rating scale that can be used in other intervention studies. We reiterate
      that this intervention is used in children without very much information so the close
      supervision following treatment may also be a benefit.
    

Intervention name(s): risperidone
Intervention type(s): Drug
Intervention description(s): liquid risperidone was administered on a mg/kg basis to a child needing seclusion. 0.015mg/kg was the start dose. Dose was increased to 0.02mg/kg if duration of episode was >30 minutes.
Intervention MeSH terms: Risperidone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: agitation; Episodes of agitation regardless of diagnosis