Antipsychotic medications are dopamine receceptor antagonists. Blocking dopamine 2 receptors reduces psychosis as well combative and explosive behaviors. Dopamine 2 receptor blockade may improve tics but also may be associated with dystonic reactions.
Typical (first generation antipsychotics, FGA)
- Rarely used, <10% of current prescriptions
- Haloperidol, chlorpromazine, fluphenazine, perphenazine, thioridazine
Atypical (second generation antipsychotics, SGA)
• Risperidone, quetiapine, aripiprazole, olanzapine, ziprasidone, clozapine, asenapine, paliperidone, iloperidone
The antipsychotic medications emerged in the 1960’s and revolutionized the treatment of schizophrenia and other severe mental illness. Use was limited in part by severe and sometimes permanent movement disorders related to dopamine blockade in the basal ganglia. This first group of medications are referred to as typical or first generation antipsychotics, and now mostly superseded by the second generation or atypical antipsychotics. The atypicals, or SGAs, have been associated with more improvement in the negative symptoms of schizophrenia and with lower risk of severe movement disorders, but are associated with greater metabolic side effects. For the remainder of this discussion, we will focus on the second generation antipsychotics.
FDA approvals for second generation antipsychotics in children are for severe mental illness including schizophrenia and bipolar disorder. Aripiprazole has an indication for Tourette’s Disorder, although alpha-agonists such as guanfacine and clonidine are more commonly used first line for Tourette’s. Aripiprazole and risperidone have been approved for use in children with autistic disorder who manifest severe irritability and aggression. This latter use should always occur in conjunction with environmental modifications and behavioral therapy and should be considered temporary.
FDA pediatric indications for atypical antipsychotics
- Schizophrenia: risperidone, olanzapine, quetiapine, aripiprazole, lurasidone (age 13+ years), asenapine (age 12+ years)
- Bipolar disorder, mixed or manic state: risperidone, quetiapine, aripiprazole, asenapine (age 10+ years)
- Bipolar disorder, depressed state: olanzapine, lurasidone (age 10+ years)
- Tourette's disorder: aripiprazole (age 6+ years)
- Irritability with Autism Spectrum Disorder: risperidone (age 5+ years), aripiprazole (age 6+ years)
Use in Pediatrics
Most pediatricians will not be managing medications for children with schizophrenia or bipolar disorder. But many pediatricians are asked to help manage aggressive behavior in children with ASD, or in neurotypical children.
Aripiprazole and risperidone are the 2 atypical antipsychotics with the most evidence for use in treatment of irritability and aggressive behaviors in children with ASD. Dosing should start low. Response may evident in hours to days.
|formulations||dosing range||dosing frequency|
|aripiprazole||2, 5, 10, 15, 20, 30 mg tablets
5 mg/ml liquid
|risperidone||0.25, 0.5, 1, 2, 3, 4 mg tablets
0.5, 1 mg ODT
1 mg/ml liquid
|0.5 - 6 mg/day||bid|
For further information:
Psychopharmacology in Children with Autism Spectrum Disorder (pdf)
- Weight gain and hyperlipidemia are common with SGAs. Aggression around food-seeking behavior may emerge. Glucose and lipid changes may be related to increased appetite leading to increased food intake, or direct metabolic effects.
- Hyperprolactinemia: may be associated with gynecomastia, galactorrhea, amenorrhea, oligomenorrhea, hirsutism, erectile dysfunction, decreased libido. Generally reversible with discontinuation of the drug. Aripiprazole, a partial D2 receptor agonist, actually decreases prolactin levels.
- Dystonia: stiffening or abnormal movements, often of face, neck, trunk. Generally emerges in the first few days of treatment. Rapidly reversible with oral or IM diphenhydramine.
- Akathisia: sense of intense restlessness, unable to be still, acute change from baseline
- Cardiac conduction changes: unclear if antipsychotic-associated prolongation of QTc is associated with increased risk of Torsade de Pointes, but baseline and monitoring ECG appropriate if positive family history, if on other meds that prolong QTc, or with ziprasidone
- Tardive dyskinesia: Irreversible stereotypical orofacial or other movements; generally emerges after years of antipsychotic use; more common with FGAs.
Adverse effect profile of commonly used SGAs
0/+ = minimal effect + = mild effect ++ = moderate effect +++ = severe effect
Adapted from C Correll in Dulcan’s Textbook of Child and Adolescent Psychiatry, 2nd edition, APPI 2016
The American Diabetes Association and the American Psychiatric Association wrote consensus guidelines on monitoring for adverse metabolic changes. In addition to metabolic monitoring, patients should be monitored for the signs and symptoms of hyperprolactinemia, and if these are present, either stop the antipsychotic and monitor for remission of symptoms, or check prolactin level and if elevated, consider further work-up for non-medication-induced etiologies.
Metabolic monitoring parameters based on consensus guidelines
|baseline||week 4||week 8||week 12||q3 months thereafter||annually|
|Personal and family history of HTN, diabetes and CV disease||X||X||X|
|weight, height, BMI||X||X||X||X||X||X|
|fasting glucose or HbA1C||X||X||X|
Antipsychotic off-label use is most commonly for aggressive behavior, often in children with ADHD.
Antipsychotic off-label use is more common in vulnerable populations:
- in younger children
- in children in foster care
- in children with intellectual disability
- in children covered by Medicaid
Problems with off-labe antipsychotic use:
- Often used for extended periods without concurrent appropriate behavioral therapy
- Rarely accompanied by recommended metabolic monitoring
- Represent a significant portion of pharmacy benefits costs in many health plans
The off- label use of antipsychotic medication in children increased dramatically beginning in the early 1990s, leveling off around 2008. Rates remain high, particularly among vulnerable populations including children in foster care, children with Medicaid, and children with intellectual disability. Despite recommendations, these medications are often used for extended periods to target behavior or symptoms without concurrent behavioral therapy or parent management training. This is particularly problematic when children whose behavioral problems are related to Post Traumatic Stress Disorder receive antipsychotics without trauma-focused cognitive behavioral therapy. Because of this, some states and some insurance plans have implemented oversight processes to review and curtail off-label antipsychotic prescribing to certain populations of children.
How long to treat and how to stop
For conditions other than schizophrenia and bipolar disorder type 1:
No child should be treated with an antipsychotic for an off-label indication “indefinitely”.
How long do we treat children with antipsychotic medications prescribed off label? For as long as needed to achieve a level of emotional and behavioral regulation that allows the child to function in home and school environments and to work in therapy to develop the skills needed to achieve that regulation without the medication. How will you know when you have gotten to that point? Get the child to a position of stability and taper the medication off and assess for ongoing or residual symptoms. Restarting the medication should only occur if symptoms recur at a level that markedly interferes with the child’s functioning. No child should be treated with an antipsychotic for an off-label indication indefinitely.
There is little evidence on best practice.
Consider decreasing by 25% of the dose every 7-10 days until gone; smaller increments may be appropriate for higher doses.
The tapering time serves in part allowing the child and family to observe behavioral responses to stopping the medication in a gradual way. There are generally not discontinuation symptoms associated with atypical antipsychotics with the rare exception of withdrawal dyskinesia associated with the rapid discontinuation of high dose, high potency antipsychotics like risperidone. Withdrawal dyskinesia presents as bizarre, often athetoid movements. Treatment: go back to previous dose and taper more slowly.