Adam, a 12-year-old autistic boy with mild intellectual disability and expressive speech delay, has been on aripiprazole, a daily 4 mg dose, for six months to help manage severe irritability. Since starting the aripiprazole, there has been a marked decrease in Adam’s aggression and self-injury, but he has gained 20 pounds. Adam will not comply with obtaining lab work to monitor for metabolic side effects of aripiprazole, and his parents wonder whether the medication could be reduced or changed.

About 1% of children ages 7–12 and about 1.5% of adolescents ages 13–18 are prescribed antipsychotic medications (Olfson M et al, JAMA Psychiatry 2015;72(9):867–874). Some are treated for FDA-approved indications such as schizophrenia, bipolar disorder, and irritability in autism (Harrison JN et al, J Pediatr Health Care 2012;26(2):139–145). However, about 65% of antipsychotic use in children and adolescents is off label, including for aggression, agitation, disruptive behavior, irritability, and augmentation in attention-deficit/hyperactivity disorder (ADHD) (Sohn M et al, Medicine 2016;95(23):e3784). We have few data on the efficacy of long-term use, but there are clear data in animals and people showing that antipsychotics can cause loss of neuronal tissue and a host of neurological and metabolic side effects. There are also data indicating that, at high doses, antipsychotics are associated with higher rates of mortality in children and adolescents. This article covers how long to use antipsychotic medications and how to safely reduce or discontinue them. 

Do antipsychotics work?

Antipsychotics can be helpful for short-term stabilization, such as to prevent psychiatric hospitalization, allow a student to stay in a less restrictive school environment, and reduce aggression or self-injury. However, research does not clearly support use in severe ADHD or oppositional defiant disorder (Lentini G et al, Biomedicines 2022;10(11):2818). Even for clinical situations with FDA approval, such as irritability in autism, consider whether the patient meets criteria for prescribing (aggression, self-injury, severe mood lability) and whether another approach might be effective, like addressing sensory or communication difficulties or using medications with safer side effect profiles. 

How long should a patient stay on an antipsychotic?

Antipsychotic use has primarily been studied and FDA approved for short-term use of up to six months in children (Aman M et al, J Child Adolesc Psychopharmacol 2015;25(6):482–493). There are few studies that assess benefits and side effects of longer-term antipsychotic use in children (Singappuli P et al, CNS Spectr 2022;27(5):570–587). Common concerns about antipsychotics include: 

• Metabolic effects (eg, weight gain, diabetes, hyperlipidemia)
• Somnolence 
• Prolonged QT interval
• Prolactin elevation
• Extrapyramidal symptoms
• Neuroleptic malignant syndrome

Plan the entire antipsychotic trial 

When you begin an antipsychotic, start with the end in mind. Talk with patients and their families about the planned duration of treatment as part of the informed consent process. Make sure to discuss the following:

• Severity of symptoms 
• The natural course of the condition
• The age of the child
• Response to other psychosocial interventions 

Since there is no defined duration for the use of antipsychotics in non-­psychotic illnesses, track the frequency and intensity of specific symptoms and decide with patients and families how much improvement and how long a period of improvement would be enough to consider reducing and discontinuing the medication. For most children and adolescents, and for most clinical indications, the duration of treatment should be as short as possible. 

When to taper

Talk with the patient and family at every appointment about the course of treatment:

• How much have presenting symptoms improved?
• Are there worrisome side effects (eg, weight gain, elevated cholesterol, somnolence, involuntary movements)?
• How compliant is the patient with the medication and monitoring?
• Is the patient or family interested in tapering off the medication?

Tapering might not be possible for patients with primary psychotic disorders or patients who have tried to taper unsuccessfully in the past. Document your rationale for continuation and regularly monitor for metabolic and movement side effects. See the AACAP Practice Parameter for the Use of Atypical Antipsychotic Medications in Children and Adolescents for monitoring recommendations (www.tinyurl.com/mpzfkp3v). 

For patients you inherit who are already on antipsychotics, revisit this decision during your evaluation. For patients who are on an antipsychotic long term, have a discussion with them every six months to determine whether the best clinical decision is to remain on the medication, given efficacy and possible side effects. Start the conversation by asking patients and families what they note as positive and negative about the medication.

How to taper

Tapering does not always mean discontinuing medication. Even small reductions may ease side effects, such as elevated cholesterol or weight gain, and reduce the risk of neurologic side effects such as tardive dyskinesia (Stroup T et al, World Psychiatry 2018;17(3):341–356). Once you and your patient decide to taper, consider these strategies.

Slow taper

• For straightforward situations with neither co-occurring conditions nor a complex medication history 
• Wait for at least three to six months of stability and a time without new stressors
• Get other support in place (eg, therapeutic intervention, school-based services, etc) 
• Reduce by about 25% of the original dose each month 
• Schedule regular appointments to check for worsening of target symptoms 

Adam and his parents report that their parent-mediated support is helping and the main problem, self-injury, has been absent for four months. You reduce Adam’s aripiprazole by 1 mg per month and see him monthly. Once at 2 mg, Adam’s problematic impulsivity returns, but he’s not as aggressive as before and has lost 3 pounds. 

Interclass medication substitution 

• For when the antipsychotic was the first medication tried or when another class of medication has efficacy for the patient’s symptoms
• For ADHD, consider stimulants or non-stimulants approved for ADHD
• For anxiety and irritability, try SSRIs
• For behavioral dysregulation or aggression related to underlying anxiety or autism, consider an alpha agonist or beta blocker

You begin Adam on extended-release methylphenidate and hold the aripiprazole at 2 mg. Over the next three months, his impulsivity improves. Adam’s parents report that Adam’s cravings for junk food have diminished. Adam starts walking to school with a friend instead of being driven. He is more settled during school and loses another 5 pounds. You reduce the aripiprazole to 1 mg, but his self-injury returns. 

Intraclass medication substitution 

• When your patient must remain on an antipsychotic due to severe symptoms (eg, psychosis, self-injury, mania), consider changing to a more weight-neutral medication like ziprasidone or lurasidone (note that it may be difficult to start with these medications due to insurance coverage)
• Also consider this strategy when a prior antipsychotic trial was not successful or when a patient presents with psychotic symptoms or mania
• Offer this option after a patient “fails” a medication like risperidone or aripiprazole due to side effects

Adam’s impulsive self-injury and mood instability overlap with bipolar depression, allowing you to obtain insurance coverage to replace the 2 mg of aripiprazole with 20 mg of lurasidone. Adam’s self-injury abates, and his weight returns to the percentile he was at before he began on aripiprazole.

CARLAT VERDICT