In recent months, the use of antipsychotic medications in children and adolescents has been debated largely because these agents are increasingly being used in youth for non-psychotic disorders and off-label indications. In addition, there has been disagreement about the validity of certain childhood diagnoses. For example, bipolar disorder data suggest that there may be a lack of psychosocial interventions for disruptive and aggressive spectrum disorders, even if antipsychotic treatment is prescribed. Furthermore, there has been concern surrounding the adverse effects related to antipsychotic use. These effects may be more severe and have long-term health implications when they occur during early human development.

“A careful risk-benefit evaluation is necessary before deciding to initiate and to maintain antipsychotic treatment in younger patients.”

Even though the debate over use of antipsychotic medications in younger patients continues, there has been an increase in the available controlled efficacy database for antipsychotics for schizophrenia, bipolar mania, and autistic disorder. In turn, this has led to FDA approval of four of the most prescribed atypical antipsychotics in youth. Aripiprazole, olanzapine, quetiapine, and risperidone have FDA-approved pediatric indications for bipolar mania and for schizophrenia. Aripiprazole and risperidone are also indicated for irritability and aggression associated with autistic disorder, and we now have controlled trial data for disruptive behavior disorders (mostly with risperidone) and tic disorders.

Assessing Tolerability

Studies comparing antipsychotic adverse effect rates in children and adolescents with those in similar adult studies have indicated that younger patients were at higher risk for a number of antipsychotic-induced side effects, including sedation, extrapyramidal side effects, withdrawal dyskinesia, prolactin elevation, weight gain, and some metabolic abnormalities. There is a concern that the time until long-term complications occur may be shorter when antipsychotic treatment is initiated during childhood. However, the data indicate that metabolic effects vary across antipsychotics. More research is needed, but it seems that weight-independent, direct metabolic effects (especially dyslipidemia) vary between individual therapies.

Strategies for Monitoring Patients

To address efficacy, safety, and tolerability issues, a careful risk-benefit evaluation is necessary before deciding to initiate and to maintain antipsychotic treatment in younger patients. Proactive and routine monitoring practices are paramount. Also, several strategies should be considered when adverse effects become distressing or concerning. After ruling out medical or substance uses, clinicians are urged to do the following to ameliorate adverse effects:

Wait for a specified time to see if tolerance develops.

Adjust doses (usually reduce them).

Provide healthy lifestyle instructions or interventions.

Switch to alternatives within or outside classes of psychotropic medications with a lower risk for a specific side effect.

Use adjunctive medication that targets a side effect.

In general, clinicians managing younger patients who are taking antipsychotics should monitor the patient’s personal and family medical history, lifestyle behaviors, height, weight, and sexual or reproductive dysfunction. Sedation, Parkinsonism, fasting blood glucose and lipids, tardive dyskinesia, blood pressure and pulse, liver function tests, electrolyte counts, full blood counts, and renal function should also be assessed at baseline and periodically thereafter. If patients are symptomatic, prolactin assessments and electrocardiograms may be necessary.

Education of patients and families about interventions to improve adverse effect rates with antipsychotic use are critical. Patients should be informed on what to expect and about the potential need for other treatment options to circumvent future problems. In cases in which these strategies fail, clinicians are urged to consult with pediatric specialists so that they can co-manage them to ensure the best possible outcomes.

 

References

Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry. 2008;47:9-20.

Correll CU, Kane JM. One-year incidence rates of tardive diskinesia in children and adolescents treated with second-generation antipsychotics: a systematic review. J Child Adolesc Psychopharmacol. 2007;17:647-655.

Correll CU, Carlson HE. Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2006;45:771-791.

Maayan L, Correll CU. Management of antipsychotic-related weight gain. Expert Rev Neurother. 2010;10:1-26.