Clinical Advisory Regarding the Use of Atypical Antipsychotic Medication in Children and Adolescents

Date of Issue: May 16, 2007

The atypical antipsychotics (second generation antipsychotics or SGAs, which include clozapine) were developed for the treatment of adults with psychotic illness.  Their use, however, has expanded to various disorders in children and adolescents, including severe behavioral disturbances in autistic spectrum and other disorders, bipolar illness, and Tourette’s syndrome.

The New York State Office of Mental Health, Division of Children and Family Services, holds that all medications, including SGAs, should only be prescribed for appropriate diagnoses, weighing risk and benefit and seeking to minimize side effects. Informed consent and education for parents/legal guardians and the child/adolescent recipient should include:

• the purpose of the each medication prescribed;
• the available evidence of its effectiveness;
• potential side effects;
• how the prescribing doctor will monitor for signs and symptoms  of problems with the medication; and
• how the medication will be reduced or stopped if it is causing problems or not achieving its desired effect. 

The following recommendations are based on a review of the current literature including the Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY); the American Academy of Child and Adolescent Psychiatry (AACAP) Practice Parameter on the use of Psychotropic Medication in Children and Adolescents; the draft AACAP Practice Parameter for the use of Atypical Antipsychotic Medications in Children and Adolescents; as well as other material referenced at the end of this advisory.  Prescribing physicians will also need to remain up-to-date with future developments or information which may impact these current recommendations.

General Principles for the Use of Atypical Antipsychotics

1. Every child and adolescent reacts individually depending on age, stage of development, differences in pharmacodynamics, pharmacokinetics, receptor binding and genetic variation in Cytochrome P450 metabolism. 
2. The dosage of the medication used and its drug/drug interactions may significantly affect both the effectiveness and tolerability of the medication.
3. The final judgment regarding care of a particular patient must be made by the  treating physician in light of all the clinical information presented by the patient, his/her family/legal guardian, the diagnostic assessment, and treatment resources available.

Recommendations for when a child/adolescent is to receive SGAs

1. Initial Assessment
   1. A careful initial diagnostic assessment must be performed with particular attention to co-morbid medical conditions, family psychiatric and medical history (including a family history of diabetes, hyperlipidemia, seizures, cardiac abnormalities and/or unexplained syncope, sudden death, or arrhythmias).
   2. Obtain psychiatric history, including exposure to drugs in utero, past history of trauma, physical/sexual abuse, dietary habits, appetite, exercise habits and day time sedation.
   3. Provide medical assessment, including vital signs, height, weight and BMI.
   4. For inpatients: admission blood work, including fasting CBC and differential, SMA-20 with lipid profile,  thyroid screen with TSH, and baseline prolactin level, as well as EKG, Abnormal Involuntary Movement Assessment (AIMS), and other diagnostic testing as needed.
2. Specific Recommendations for the use of SGAs:
   1. Medication should never substitute for other treatment modalities.  Psychopharmacological treatment should be incorporated into the treatment plan in the context of the overall therapeutic plan.
   2. SGAs should not be the sole treatment for severe aggression except when the aggression or behavioral dyscontrol is a manifestation of a diagnosis for which the medication is indicated.  Medication should be used when appropriate behavioral interventions have not been successful or when aggression has the potential for imminent harm.
   3. Every facility or clinic should have a clearly delineated maximum dosage for each medication and a system of review and approval for use above this dosage.  Since the bioavailability of the active medication can vary dramatically, treatment with higher than generally studied doses should be considered for patients with suboptimal response and lack of limiting adverse effects but only after review and authorization by the Clinical Director equivalent, or designee.
   4. Follow the dosing guideline of “Start Low and Go Slow.”
   5. Use the fewest possible medications possible. When multiple medications are used monitor closely and reassess regularly for effectiveness and side effects. Minimize polypharmacy, e.g. the use of two or more SGAs, by continuing cross-titration until the initial SGA has been discontinued.
   6. Avoid abrupt discontinuation of any SGA, tapering slowly whenever possible.
   7. If one SGA fails consider another SGA or a medication from a different class. Consider clozapine when two or more SGAs have not been effective. 
3. Family Education and Consent
   The family/legal guardian should be fully informed of risks, benefits and alternative treatments. Written information should be supplied when available and in the primary language of the family. Families should be provided ample time for questions and discussion before consent is requested.   Parent/guardian consent provisions are contained in Mental Hygiene Law Section 33.21.
4. Ongoing Monitoring
   1. Vital signs, weight, height and BMI should be monitored regularly during initiation of treatment and then at least every three months. 
   2. Fasting blood glucose and lipid levels should be obtained at least at three months and at six monthly intervals thereafter.  Testing should be ongoing every three months or more frequently for patients who gain significantly amounts of weight, have a family history of diabetes or show possible signs of hyperglycemia (e.g. new onset polydipsia, non-lithium induced polyuria, lack of appetite, unintended weight loss, somnolence).
   3. EKG abnormalities or a family history of cardiac abnormalities or sudden death at a young age should be a trigger for increased monitoring and consultation.
   4. Use a standardized pediatric side effect scale such as the SMURF (Safety Monitoring Uniform Report Form) or the TRAAY Antipsychotic Side Effect Checklist at baseline and regular intervals, initially monthly and then at least every three months after stabilization on the medication.
   5. Obtain a baseline and yearly prolactin level.  When symptoms of elevated prolactin occur, such as amenorrhea/oligomenorrhea, galactorrhea or gynecomastia, obtain at least quarterly prolactin blood levels.
   6. Repeat blood work at least every six months on all patients on SGAs. An AIMS and EKG should be obtained at least yearly.
   7. Monitor specific medications as necessary (e.g., follow Clozapine guidelines for WBC/ANC blood testing and monitor EKG during titration of Ziprasidone).

Medications can provide invaluable help for children and adolescents. It is our work to maximize their benefits, to reduce risk to the extent possible and to engage patients and families in the care process.

Bibliography

AACAP Practice Parameter on the use of  Psychotropic Medication in Children and Adolescents.

AACAP (Draft) Practice Parameter for the use of Atypical Antipsychotics Medications in Children and Adolescents.

Correll CU, et al (2006), Recognizing and Monitoring Adverse Events of Second Generation Antipsychotics in Children and Adolescents.  Child Adolesc Psychiatr Clin N Am 15:177-206.

Correll CU and Carlson HE (2006), Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents. J Am Acad Child Adolesc Psychiatry. 45:7, pp 771-791.

Findling, RL, et al (2004), Atypical Antipsychotics in the Treatment of Children and Adolescents: Clinical Applications. J Clin Psychiatry, 65 (suppl 6).

Findling, RL, et al (2005),  Use of Antipychotics in Children and Adolescents. J Clin Psychiatry 66 (suppl 7) 29-40.

Gerbino-Rosen G. et al (2005), Hematological adverse events in Clozapine-treated children and adolescents. J AM Acad Child Adolesc Psychiatry 44: 1024-31.

Greenhill, LL et al (2004), Comparison of Increasing Detailed Elicitation Methods for the Assessment of Adverse Events in Pediatric Psychopharmacology. J Am Acad Child Adolesc Psychiatry 43(12): 1488-96.

Kranzler, HN, et al (2006), Treatment-refractory Schizophrenia in Children and Adolescents: An update on clozapine and other pharmacologic interventions. Child Adolesc Psychiatric Clin N AM 15:35-159.

Kranzler, HN et al (2005), Clozapine: Its impact on aggressive behavior among children and adolescents with schizophrenia. J AM Acad Child Adolesc Psychiatry 44:55-63.

Papadopoulos E et al (2003), Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY). Part II. J Am Acad Child Adolesc Psychiatry 44:145-161.

Schur SB et al (2003), Treatment recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY). Part I. J Am Acad Child Adolesc Psychiatry 44: 132-44.