Objectives: To measure the timing and frequency of follow-up care during the initiation phase of antidepressant therapy, and to compare the typical pattern of care with current product guidelines.
Study Design: Retrospective cohort study.
Methods: The study included 84 514 adult and pediatric patients who started a new course of antidepressant therapy for any indication between July 2001 and September 2003. Patients were members of a large managed care organization in the northeastern United States. Ambulatory visits during the first 12 weeks of treatment were identified using medical claims data. Outcome measures were time to first follow-up visit, frequency of follow-up visits, and percentage of patients receiving recommended levels of care.
Results: During the first 4 weeks of treatment with antidepressants, only 55.0% of patients saw a healthcare provider for any purpose, and only 17.7% saw a provider for mental healthcare. Ambulatory visit rates during the first 4, 8, and 12 weeks were significantly lower than the minimum levels recommended in product labeling (P <.0001). Only 14.9% of patients received the Food and Drug Administration-recommended level of follow-up care during the first 4 weeks, 18.1% at 8 weeks, and 22.6% at 12 weeks.
Conclusions: Adults and children who begin a new course of antidepressant therapy tend to receive far less monitoring than is recommended in current product labeling. Given safety concerns during the initiation phase, earlier and more frequent follow-up care appears desirable. Further research is needed to identify the most cost-effective schedule of care.
(Am J Manag Care. 2006;12:453-461)
In October 2004, the Food and Drug Administration (FDA) directed manufacturers to include a new "black box" warning and expanded warning sections in the labeling for all antidepressant products.1-3 The new labeling warns healthcare providers about the increased risk of suicidal thoughts and actions ("suicidality") in children and adolescents who take antidepressant medications for any indication, including major depressive disorder and obsessive-compulsive disorder (OCD). The FDA also developed a patient medication guide on the risk of suicidality and the precautions that can be taken by patients, parents, and caregivers.2,4 These regulatory actions were based on a combined analysis of adverse events in 24 clinical trials that studied the use of antidepressant drugs in pediatric populations. When results were pooled across all drugs and all indications, the analysis showed a small but statistically significant increase in suicidality risk for antidepressants (compared with placebo) during the first few months of treatment.5,6
The new warning labels advise healthcare providers to monitor pediatric patients closely for signs of clinical worsening, suicidality, or unusual changes in behavior, especially during the first few months of a new course of antidepressant therapy or after a change in dose.3 The warning labels recommend a specific pattern of followup care: at least weekly face-to-face visits during the first 4 weeks of treatment, visits every other week during the next 4 weeks, a visit at 12 weeks of treatment, and visits as indicated clinically beyond that point. Additional contacts by telephone as needed are encouraged between the face-to-face visits. More concentrated monitoring during the early stages of treatment is recommended because there is some evidence that the risk of suicidality may be higher during the first few weeks of treatment.7
Although the risk of suicidality in children and adolescents has been the primary focus of public and regulatory attention, the FDA also has begun to address the possibility of an increased risk of suicidality in adult users of antidepressants.1,8,9 Warnings about this risk were first introduced into the labeling of selected products in March 2004, and they were expanded and applied to all antidepressant products in October 2004.1,8 The new product labels recommend "close monitoring" of adult patients for signs of clinical worsening or suicidality, especially during the first few months of a new course of therapy for depression, and they recommend an intensive pattern of follow-up visits similar to the pattern recommended for pediatric care.3 In June 2005, the FDA announced that it had begun a comprehensive analysis of adult clinical trial data (similar to the combined analysis of pediatric trial data) in an effort to create a stronger evidentiary basis for future regulatory actions in this area.9
The new suicidality warnings build on a broader framework of clinical practice guidelines for the use of antidepressants in the treatment of depression, anxiety disorders, and other conditions. These guidelines have been developed most extensively for the treatment of depression in adults,10-16 whereas relatively few have been developed for the pharmacological treatment of anxiety disorders17-19 or for pediatric use of antidepressants for any indication. Guidelines for the treatment of depression call for close monitoring of patients during the acute phase of treatment, which generally lasts a few months and ends with remission of symptoms.10,11 The primary goals of monitoring are to assess the effectiveness of therapy, identify side effects, monitor the patient's condition, adjust therapy as needed, and promote adherence.10-12 Guidelines for the treatment of anxiety disorders also call for close monitoring of patients who receive medication therapy.17-19
Guidelines vary widely in the recommended frequency and timing of follow-up visits for patients who begin a new course of antidepressant therapy. The American Psychiatric Association recommends a vigorous schedule of monitoring during the acute phase of treatment for depression—at least weekly contacts in routine cases and multiple contacts per week in more complex cases.10 Monitoring contacts are defined broadly to include face-to-face visits, telephone contacts, or contacts with other knowledgeable clinicians, depending on the circumstances.10 In an earlier set of guidelines, the Agency for Health Care Policy and Research recommended face-to-face visits every 10 to 14 days during the first 6 to 8 weeks of treatment for patients with less severe depression, and weekly visits in more severe cases.11 Other clinical guidelines recommend follow-up contacts on a weekly, biweekly, or monthly basis, depending on a variety of factors.12-16 The FDA guidelines fall roughly in the middle of this range—weekly face-to-face visits during the first month, tapering to monthly face-to-face visits by the third month.
Many studies have examined patterns of treatment response to antidepressant medications, but only a few have reported data on the typical frequency of follow-up visits for adult or pediatric patients who initiate antidepressant therapy in usual practice.20-24 The limited available data suggest that follow-up visit rates tend to be low,21,23,24 but none of these studies provide a direct measure of the concordance between usual practice and the new FDA guidelines. The most commonly used measure of visit frequency was developed by the National Committee for Quality Assurance to assess the pharmacological management of depression.21,25 As defined in Health Employer Data and Information Set (HEDIS) specifications, "optimal practitioner contact" frequency is a minimum of 3 follow-up visits for mental healthcare during the first 12 weeks of a new treatment episode; at least 2 of the measured visits must be face-to-face, and 1 may be a telephone contact.25 This metric is useful for evaluating the overall quality of care, but it is not well suited to measuring the concordance of current practice with the new FDA guidelines for antidepressant products. The HEDIS metric is limited to patients with depression (rather than any condition treated with antidepressants), it provides no information on the follow-up care received by pediatric patients (because the metric is defined only for adults), and it provides no information on the time course of visits during the first 12 weeks of care. Without more comprehensive benchmark data, it is difficult to gauge whether the pattern of care defined in the new product labeling is feasible and realistic in the context of current practice.
The objectives of this study were to measure the timing and frequency of follow-up visits during the initial phase of antidepressant therapy, and to compare the typical pattern of care with the pattern recommended in product labeling. The design of the study mirrored the scope and content of the new FDA guidelines. The study measured the time course of face-to-face visits for any patient (adult or pediatric) who began using an antidepressant medication for any treated condition, and it compared the typical pattern of visits with the time course recommended in product guidelines. Although the new guidelines apply equally to all pediatric users, we measured visit frequency separately for 3 pediatric age groups (0-6 years, 7-12 years, and 13-18 years), because of the wide variations in treated conditions and incidence of use across these groups.
Patients were participants in medical and pharmacy benefit plans administered by a large managed care organization in the northeastern region of the United States; the medical plans included coverage for mental healthcare. The study population included all plan participants who had combined eligibility for medical and pharmacy benefits at any time during the study period, which extended from January 1, 2001, through December 31, 2003. A total of 2 411 316 plan participants met the criteria for inclusion.
Medical utilization data (including mental health claims data) were drawn from an administrative claims database maintained by the managed care organization. Drug utilization data were drawn from a prescription claims database maintained by Medco Health Solutions, Inc, the pharmacy benefits management company that manages the prescription benefit plans for this population. Medical and pharmacy claims data were integrated at the patient level; personal identifying information was not retained.