Discontinuing Antipsychotics

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“Bridget,” a 15-year-old girl, is referred by her foster care case manager for continued aggression. She has diagnoses of attention-deficit/hyperactivity disorder (ADHD), conduct disorder, and posttraumatic stress disorder (PTSD) related to sexual abuse she experienced in a stepfamily setting from 9 to 12 years of age. Her mother is receiving inpatient behavioral health care in an extended stay program. Bridget’s father is not available, and her 2 younger siblings are in different foster care settings. Bridget is currently prescribed risperidone 3 mg daily, methylphenidate extended-release 54 mg daily, and clonidine immediate-release 0.2 mg nightly.

Approximately 1% of children aged 7 to 12 years and 1.5% of individuals aged 13 to 18 years are prescribed antipsychotic medications, according to findings from a study.¹ These medications are sometimes US Food and Drug Administration (FDA) approved for conditions such as schizophrenia, bipolar disorder, and irritability associated with autism.² However, approximately 65% of antipsychotic medications for children and adolescents are prescribed for off-label uses, including managing aggression, agitation, disruptive behaviors, and irritability as well as adjunct treatment for ADHD.³ Although there are limited data on the long-term effectiveness of these medications, research has shown that they can lead to a reduction in neuronal tissue and various neurological and metabolic adverse effects.⁴ Additionally, high doses of antipsychotics have been linked to increased mortality rates in this age group.^5,6 This article expands on our previous work and discusses the appropriate duration for antipsychotic use and strategies for safely tapering or discontinuing them.⁷

First Things First: Is There a Need?

Although frank psychosis and bipolar mania remain clear indications for use or consideration of dopamine receptor 2 (D₂)–blocking antipsychotic medications, in these circumstances and in all other cases, a comprehensive assessment is warranted to clarify the diagnoses and options for addressing the symptoms. For example, the differential diagnosis for an agitated teenager with seemingly mixed mania may include malignant catatonia, for which antipsychotic medication is generally contraindicated, as it is likely to exacerbate the condition.⁸ This is particularly more common in patients with autism.^9,10 Another more common concern is aggression associated with ADHD; Blader found that well-crafted trials of stimulant medications (eg, first trying methylphenidate and then trying dextroamphetamine) were effective for managing aggression in approximately 60% to 80% of young patients.¹¹ Given the potential severity of metabolic and neurologic adverse effects of antipsychotic medications, we wrote treatment algorithms to begin with nonpharmacological approaches and treatment of co-occurring conditions before approaching the use of antipsychotics. We also made recommendations for monitoring patients during their use and, once patients are stable, looking at whether, when, and how these medications might be discontinued.¹²

How Well Do Antipsychotics Work?

Antipsychotics can be beneficial for short-term stabilization, such as preventing psychiatric hospitalization, helping a student remain in a less restrictive school environment, and reducing aggression or self-harming behaviors. However, the evidence does not strongly support their use in treating severe ADHD or oppositional defiant disorder.¹³ Even in cases where there is FDA approval, such as for managing irritability in autism, it is important to assess whether the patient meets the criteria for antipsychotic treatment (eg, aggression, self-injury, severe mood instability) and whether other approaches might be effective. This could include addressing sensory or communication challenges or considering medications with a safer adverse effect profile.

For How Long Should They Be Used?

The use of antipsychotic medications in children has primarily been studied and approved by the FDA for short-term treatment, generally up to 6 months.¹⁴ There is limited research on the long-term benefits and adverse effects of antipsychotic use in children.¹⁵ Concerns commonly associated with antipsychotic medications include the following:

• Metabolic effects (such as weight gain, diabetes, and hyperlipidemia)
• Somnolence
• Prolonged corrected QT interval
• Elevated prolactin levels
• Extrapyramidal symptoms
• Neuroleptic malignant syndrome

How long should you use these medications? It will not always be possible to reduce D₂-blocking antipsychotic medications, because some patients have symptoms related to psychosis or affective conditions that do not respond to other approaches and where the benefits of continuing the medication outweigh the risks, perhaps keeping the patient safe and/or functioning. We recommend that you use them with an intent to reduce and discontinue their use whenever and however possible, such as when an episode of mania has passed, when you can build a more robust therapy or community plan to support the patient, or when you can substitute less toxic medications, such as antiepileptic drugs for mood stability or stimulant medications for aggression in ADHD, as noted previously. Given these considerations, how do we minimize the use of D₂-blocking antipsychotic medications?

Start With Discontinuation in Mind

When initiating antipsychotic medication, it is crucial to consider the end goal from the start. As part of the informed consent process, discuss the intended duration of treatment with patients and their families. Important topics to cover include the following:

• The severity of symptoms
• The natural progression of the condition
• The child’s age
• The response to other psychosocial treatments

Since there is no set duration for antipsychotic use in nonpsychotic conditions, it is important to monitor the frequency and severity of specific symptoms. Collaborate with patients and families to determine the desired level and duration of improvement that would justify tapering or discontinuing the medication. As a possible guideline, when we use selective serotonin reuptake inhibitors (SSRIs) for depression, we like to see at least 6 to 12 months of remission before we consider tapering and to look at any seasonal or stress-related aspects such as fall/winter effects, school-related stress, or even loss of school structure. Still, the treatment period should be as brief as possible for most clinical situations in children and adolescents.¹⁶

When to Reduce Antipsychotics?

At each appointment, discuss the ongoing treatment plan with the patient and their family, focusing on the following:

• How much improvement has occurred since the initial symptoms?
• Are there concerning adverse effects (eg, weight gain, elevated cholesterol level, drowsiness, involuntary movements)?
• How well is the patient adhering to the medication regimen and required monitoring?
• Are the patient and family open to the idea of tapering the medication?

Tapering may not be feasible for patients with primary psychotic disorders or severe mood instability or those with previous failed tapering attempts. If there are ongoing symptoms, take another look at the differential diagnosis and possible treatment options. You do not want to continue ineffective treatment with potentially severe adverse effects. In any case, if you are continuing the medication, you should document the reasons for doing so and consistently monitor for metabolic and movement-related adverse effects. Refer to the American Academy of Child and Adolescent Psychiatry’s Practice Parameter for the Use of Atypical Antipsychotic Medication in Children and Adolescents for monitoring guidelines.¹⁷

When you take over care for patients already taking antipsychotic medications, reassess the decision to continue them during your evaluation. For patients on long-term antipsychotic treatment, revisit this discussion every 6 months to evaluate whether continuing the medication remains the best option, considering its effectiveness and potential adverse effects. Begin these conversations by asking patients and families what they perceive as the benefits and drawbacks of the medication.

How Slow Should You Go?

Tapering does not necessarily mean discontinuing the medication entirely. Even minor dose reductions can help alleviate adverse effects such as elevated cholesterol level or weight gain and lower the risk of neurological adverse effects, such as tardive dyskinesia.¹⁸ Once you and your patient agree to taper, consider the following strategies:

• This is ideal for straightforward cases without co-occurring conditions or a complicated medication history.
• Ensure at least 3 to 6 months of stability and choose a time without new stressors.
• Arrange for additional support (eg, therapeutic interventions, school-based services).
• Reduce the dose by no more than approximately 25% of the original dose every 3 to 6 months or 5% to 10% every 2 months.¹⁹ Although there are no clear data to guide the rate of the dosage reduction in children and teenagers, adult research supports very gradual reduction over many months to 2 or 3 years to reduce relapse rates of psychosis in patients who have been on long-term antipsychotic treatment.
• Consider gradual weekly reductions toward the new dose (eg, recommending the patient take the current dose daily and then substituting the new lower target dose for 1 of 7 days the first week, 2 of 7 days the second week, etc, until every day is at the new lower dose).
• Schedule regular follow-ups to monitor for any worsening of target symptoms.

Bridget is now receiving therapy for her PTSD, and you have stabilized her aggression by shifting her from methylphenidate to dextroamphetamine. However, she is gradually gaining weight, and you decide to reduce her risperidone to 2.5 mg daily using a gradual weekly reduction over 6 weeks.

Is Switching Medication an Option?

In many situations, you can effectively substitute the antipsychotic or reduce it substantially by using other less potentially toxic medications, such as in the following suggestions:

• For ADHD with aggression, consider using different kinds of stimulants or even nonstimulant ADHD medications.
• If there is cooccurring anxiety or irritability, consider trying SSRIs.
• For behavioral dysregulation or aggression associated with underlying anxiety or autism, explore options such as α agonists or β-blockers.

After 6 months, you have reduced Bridget’s risperidone to 0.5 mg daily. Her aggression is well managed, she is making friends, and she is doing better academically, although her appetite and weight have not stabilized. You attempt to discontinue the risperidone altogether, but Bridget becomes far more agitated.

Intraclass Medication Substitution

When a patient needs to stay on an antipsychotic due to severe symptoms (such as psychosis, self-injury, or mania), consider switching to a more weight-neutral option such as ziprasidone or lurasidone (keeping in mind that insurance coverage might make these medications challenging to start). This approach is also worth considering if a previous antipsychotic trial was unsuccessful or if the patient presents with psychotic symptoms or mania. Offer this alternative if a patient experiences adverse effects that lead to discontinuation of a medication such as risperidone or aripiprazole.

Bridget has stability on ziprasidone 20 mg along with the dextroamphetamine and clonidine. Screening and follow-up ECG results are normal, and her weight gain has stabilized. Bridget’s mother is in a step-down psychiatric placement facility, and the family is beginning therapy aimed at possible reunification.

Concluding Thoughts

Antipsychotics can be lifesaving, but they should only be used when necessary and when accompanied by continuous discussions about the length of treatment and strategies to minimize dosage and adverse effects.

Dr Feder is a clinical and forensic child and family psychiatrist in Solana Beach, California. He is also the editor in chief of The Carlat Child Psychiatry Report. Dr Patel Rao is medical director at Vista Hill Foundation in San Diego, California; clinical professor in the University of California San Diego Department of Psychiatry; and president of the local San Diego regional chapter of the American Academy of Child and Adolescent Psychiatry.

References

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