The definition of “off-label” is the specific administration of a medication for a use that is not included in the FDA package insert for that medication. Thus, medications may be used for different age groups, doses, and duration that are not specifically addressed in the product labeling1. Further, combination treatment2 is not commonly covered by product labeling including: treating comorbid psychopathology, when monotherapy is ineffective, or to help lessen the adverse effects of another medication. While there are FDA approved combination treatments, most combinations are considered off-label use.
For some indications, “older” medications may have FDA approval based on a prior approval process that used extrapolation from adult studies as opposed to pediatric testing. However, “newer” treatments may be preferred due to efficacy and/or tolerability as determined via pediatric research. Another increasing use of “off-label” medications3,4 is when youth exhibit impairment but do not meet threshold criteria for a specific disorder. Those children with subthreshold symptoms for approved disorders have impairment and can benefit greatly from treatment with medication that has proven efficacy in the disorder.
AACAP’s website contains a toolkit for monitoring symptoms and response to medications. A parent AACAP resource is the Parents Medication Guide series covering use of medications for psychiatric disorders.
Off-label medication use is part of the standard of care in the treatment of psychiatric disorders when: 1) there is a solid evidence base for the medication; 2) an off-label medication has better efficacy and/or safety evidence than an on-label one; 3) a child has symptoms that are not controlled by, or experiences unacceptable side effects due to, an on-label medication; 4) a child has a disorder or comorbid conditions for which there is no FDA-approved treatment; 5) adjunct medication is necessary for control of side effects of another medication; and/or 6) a child is below the age for which an FDA approved treatment is available.
- Off-label use of drugs in children. Frattarelli DA, Galinkin JL, Green TP, Johnson TD, Neville KA, Paul IM, Van Den Anker JN; American Academy of Pediatrics Committee on Drugs. Pediatrics. 2014 Mar;133(3):563-7. doi: 10.1542/peds.2013-4060. Epub 2014 Feb 24. Review.
- Combined pharmacotherapy: An emerging trend in pediatric psychopharmacology. Wilens TE, Spencer TJ, Biederman J, Wozniak J, Connor D. J Am Acad Child Adolesc Psychiatry. 1995; 34:110-112.
- Trends in subthreshold psychiatric diagnoses for youth in community treatment.
Safer DJ, Rajakannan T, Burcu M, Zito JM.
JAMA Psychiatry. 2015 Jan;72(1):75-83. doi: 10.1001/jamapsychiatry.2014.1746.
- Child and adolescent psychiatrists' reported monitoring behaviors for second-generation antipsychotics. Rodday AM, Parsons SK, Mankiw C, Correll CU, Robb AS, Zima BT, Saunders TS, Leslie LK. J Child Adolesc Psychopharmacol. 2015 May;25(4):351-61. doi: 10.1089/cap.2014.0156. Epub 2015 Apr 28.
- Pediatric psychopharmacology: food and drug administration approval through the evidence lens. Lorberg B, Robb A, Pavuluri M, Chen DT, Wilens T. J Am Acad Child Adolesc Psychiatry. 2014 Jul;53(7):716-9. doi: 10.1016/j.jaac.2014.04.015. No abstract available.