Newer antidepressants are an important treatment option to be considered for youth with some of the most common and life-threatening psychiatric illnesses. There have, however, been significant controversies about possible severe adverse effects of pediatric use of antidepressants. Meta-analytic findings from the U.S. Food and Drug Administration (FDA) prompted a black box warning, first in 2004, because antidepressant medication likely increases the risk of suicidal thoughts or behaviors in some children and adolescents. 1,2 An increased risk was also found in a subsequent meta-analytic review, although the benefits of antidepressants appeared to be much greater than the risk for suicidal ideation and behavior for most young people. 3
As a result, organizations recommend physicians appropriately monitor youths who have been prescribed antidepressant medications. This article will discuss the essential elements of a monitoring approach for pediatric antidepressant use, an interactive voice response (IVR) computer system that incorporates these elements, a pilot study, and preliminary trial results.
Essential monitoring elements
Based on the FDA black box warning and subsequent revisions, we derived several essential monitoring elements, including the need for: (1) clinically sufficient monitoring, (2) a focus on potential side effects, (3) provisions for risk assessment and possible intervention when side effects are detected, and (4) a limit on the demands placed on providers and families.
Clinically sufficient monitoring. With regard to frequency, initial FDA monitoring guidelines included provider contact weekly for the first four weeks of treatment, biweekly for the next four weeks, at 12 weeks, and as clinically indicated after 12 weeks.4 Though this frequency is not specified in the most recent label revisions, current recommendations state that patients need to be “monitored appropriately and observed closely,” with monitoring most important at initiation of treatment or following dose changes.5
A focus on potential side effects. As indicated in the FDA guidelines, this focus would include the principal risk of “suicidality” as well as “clinical worsening” indicated by new, more frequent, and/or more intense symptoms related to pediatric antidepressant use. Symptoms and/or potential side effects include depression, anxiety, trouble sleeping, anger or aggression, and/or mania or agitation.6 Medication adherence would also require monitoring given the risks associated with stopping an antidepressant suddenly.6
Provision for risk assessment and possible intervention when side effects are detected. Though not specifically stated in the FDA recommendation, standardized, research-based methods and criteria should be used to assess risk, consider possible side effects, and determine potential interventions.
Minimize demands on providers and families. Adhering to FDA guidelines, such as those for pediatric antidepressant use, generally involves increased professional contact with either a psychiatrist or primary care physician. However, this can be complicated given the shortage of child and adolescent psychiatrists, a lack of access by primary care to psychiatric decision support, and questions about whether primary care physicians can be reimbursed for medication management visits.7,8 In addition, increased monitoring could stress families if more frequent appointments cause transportation problems or financial concerns.9
Monitoring use via an IVR computer system
To address these concerns and allow convenient, timely monitoring of children and adolescents receiving antidepressant meds, researchers at Nationwide Children's Hospital (NCH) in Columbus, Ohio developed the Pharmaceutical and Safety Tracking (PhaST) system. PhaST is an interactive voice response computer system that generates seven automated phone calls within the three month period following a new pediatric antidepressant prescription.
During each call, the respondent is asked eight screening questions inquiring about medication adherence and potential side effects, as shown in Table 1. The calls, which are timed to occur at the initiation of treatment and during potential dose changes, provide clinically sufficient monitoring in accord with FDA monitoring guidelines. Respondents may answer each question by pushing numbers on the phone's key pad. They may supplement their replies by leaving a voice message.
If a concern is detected during a monitoring call, an on-call PhaST triage staff (PTS) member is paged. When the page is received, the staff member becomes responsible for providing risk assessment and possible intervention when side effects are detected.
This is done by logging into a Web-based application (PhaST Web) that provides data from the screening call and research-based guidance that is used to gather additional details about patient symptoms, determine the patient's current level of risk, and decide what, if any, additional interventions or actions are required. As each monitoring call is completed, an e-mailed report is issued to the patient's care provider, detailing initial screening results, any PTS risk assessment information and subsequent actions.