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Monitoring pediatric antidepressant use
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.
By using telephone calls and IVR technology, the PhaST system thus minimizes monitoring demands on providers and families. Because the monitoring calls can screen for potential concerns and provide routine reports, on-call triage, and patient contact, subsequent physician contact or action is needed only when an immediate risk is detected. The technology also simplifies the monitoring process for the patient's family, since calls are conveniently scheduled and additional transportation or treatment costs occur only if medically required.
Table 1: PhaST Monitoring Call Screening Questions
Domain | Adolescent (≥ 13 years old) IVR Question “Since the last doctor visit or phone checkup… | Parent IVR Question “Since the last doctor visit or phone check up… |
Depression | …have you had new or increased problems with sadness or depression?” | …has your child had new or increased problems with sadness or depression?” |
Anxiety | …have you had new or increased problems with worry, fear, anxiety, or panic?” | …has your child had new or increased problems with worry, fear anxiety, or panic?” |
Insomnia | …have you had new or increased problems sleeping?” | …has your child had new or increased problems sleeping?” |
Agitation or Mania | …have you had changes in mood, more energy than usual, or behavior that you or others don't like, or that worry you or others?” | … have you noticed any new problem behaviors, changes in mood, or more energy than usual in your child?” |
Aggression/Anger | …have you been a lot more angry, irritable, or getting into fights or arguments with others?” | …has your child been a lot more angry, irritable, or prone to get into fights or arguments with others?” |
Open-Ended | …have there been any other new or unusual changes in your feelings, behavior, or health that concern you?” | …have there been any other new or unusual changes in your child's feelings, behavior, or health that concern you?” |
Suicidality | …have you had thoughts about ending your life?” | …has your child said or done anything suggesting that <insert ‘he’ or ‘she’> might want to hurt <insert ‘himself’ or ‘herself’>?” |
Pilot study results
Between November 2007 and February 2008, a pilot study, involving a licensed psychologist, tested the PhaST screening questions and risk assessment process. Seventeen patients were referred by their psychiatrists after agreeing to consider participation in the pilot study. Of these, 11 patients were enrolled and ten completed all six monitoring calls in accord with the FDA monitoring schedule. On average, each completed call required 1.52 attempts to obtain a respondent reply (range = 1-9 attempts).
The ten respondents who completed all six calls rated the screening questions as easy to answer and understand. Eight believed that the calls would help the patient's doctor know more about how the patient was doing, while nine believed the follow-up calls would help protect the patient from harm. Clinicians provided with monitoring call information stated that they found it valuable.
Of the 61 who completed monitoring calls in the pilot, 33 percent were “positive” for side effects and/or medication non-adherence. Concerns reported ranged from medication non-adherence and/or sleepiness to aggression, thoughts of death, and/or self-injurious behavior. All participants believed the questions asked during the risk assessment were helpful in determining next steps.
Current PhaST study trial
Information obtained during the pilot study informed the current randomized trial, funded by AHRQ (R18HS017258; PI: Gardner), that compares PhaST and usual care in a large, urban pediatric healthcare system serving primarily a Medicaid population. The trial began in September 2008 and continues through December 2010. The trial involves youth, from six to 17 years of age, who are referred by physicians at NCH or NCH-affiliated community medical practices following a new prescription for antidepressant medication.
Incidence of Problems
While outcome results regarding the effectiveness of the PhaST system are not yet available, we have preliminary data regarding recruitment efforts and the feasibility of completing study monitoring calls. As of September 1, 2009, 160 patients have been referred to the study with 77 (48 percent) of the referred patients enrolled in the study. The 34 participants in the PhaST condition completed 219 of 602 monitoring calls (35 percent success rate) during the first 11 months of the study.
As shown in Figure 1, 28 participants in the PhaST condition reported at least one problem during monitoring. Fourteen (41 percent) reported increased depression and six (18 percent) reported suicidality. High rates of anger, mania, sleep problems, and medication non-adherence were also detected. Following “positive calls,” PTS clinicians provided risk assessments and clinical intervention as needed.
Summary
The PhaST system was developed to improve monitoring efforts of pediatric antidepressant use and is currently being tested in a clinical trial. The design of PhaST reflects both the FDA recommendations and consideration of system and family resources. Pilot and preliminary results of the current study data have shown that participants can be reached by telephone and necessary monitoring calls can be completed over a period of time.
PTS clinicians were also able to respond to “positive calls” and determine level of concern as well as action steps needed. Physicians and other ongoing providers received monitoring call reports and PTS clinician follow-up as indicated. Given the promising findings of the pilot study and preliminary trial data, PhaST appears to be a sensitive method for monitoring outpatients for adverse effects of antidepressants. Because it uses inexpensive IVR technology and physician extenders, it may prove to increase communication between health providers and patients and shows promise for improving patient safety and quality of care.
Beyond medication safety, it could also be utilized to enhance medication and/or treatment adherence, as well as assist clinicians in helping patients implement behavior management plans.
References
- Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry, 2006; 63:332-339.
- U.S. Food and Drug Administration. FDA public health advisory: Suicidality in children and adolescents being treated with antidepressant medications, 2004. https://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm. Accessed March 30, 2009.
- Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: A meta-analysis of randomized controlled trials. Journal of American Medical Association, 2007; 297:1683-1696.
- U.S. Food and Drug Administration. Class suicidality labeling language for antidepressants, 2005. Available at: https://www.fda.gov/cder/drug/antidepressants/PI_template.pdf. Accessed March 30, 2009.
- U.S. Food and Drug Administration. Revisions to Product Labeling, 2007a. Available at: https://fda.gov/cder/drug/antidepressants/antidepressants_label_change_2007.pdf. Accessed March 30, 2009.
- U.S. Food and Drug Administration. Revisions to Medication Guide, Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions, 2007b. Available at: https://www.fda.gov/downloads/Drugs/DrugSafety/ InformationbyDrugClass/ucm100211.pdf. Accessed October 19, 2009.
- Kim WJ. Child and adolescent psychiatry workforce: A critical shortage and national challenge. Academic Psychiatry 2003; 27 (4): 277-282.
- Rushton J, Bruckman D, Kelleher K. Primary care referral of children with psychosocial problems. Archives of Pediatric Adolescent Medicine, 2002; 21 (5): 323-331.
- Flisher AJ, Kramer RA, Grosser RC, Alegria M, Bird HR, Bourdon KH, Goodman SH, Greenwald S, Horwitz SM, Moore RE, Narrow WE, Hoven CW. Correlates of unmet need for mental health services by children and adolescents. Psychological Medicine, 1997; 27, 1145-1154.
Behavioral Healthcare 2010 November-December;30(10):19-21
