Research report
Chronic forms of major depression are still undertreated in the 21st century: Systematic assessment of 801 patients presenting for treatment

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Abstract

During a multisite, NIMH-sponsored clinical trial entitled, “Research Evaluating the Value of Augmentation of Medication by Psychotherapy” (REVAMP), we assessed the adequacy of prior antidepressant treatment in patients with chronic forms of major depressive disorder using the Antidepressant Treatment History Form (ATHF). We hypothesized that when compared to earlier studies treatment adequacy would not have increased over the past decade.

We found that only 33% of the 801 subjects enrolled had ever had a prior adequate trial of antidepressant medication. Patients significantly more likely to have received prior adequate antidepressant trials were older, married, white, had a longer duration of illness, had more melancholic features or met criteria for the melancholic subtype or met lifetime criteria for panic disorder.

The hypothesis that rates of treatment adequacy have not significantly increased over the past decade was supported. These results and the consistency of similar results over time point to the dire need for patient and provider education regarding the signs and symptoms of depression and its treatment.

Introduction

A consensus conference on reasons for the undertreatment of depression was organized and held by the National Depressive and Manic Depressive Association (NDMDA) in 1996. The conference concluded that there was overwhelming evidence that individuals with depression were being seriously undertreated in spite of the fact effective treatments were available. Quoting from the report, “The cost to individuals and society of this undertreatment is substantial. Long suffering, suicide, occupational impairment, and impairment in interpersonal and family relationships exist. Efforts to redress this gap have included provider educational programs and public educational programs. Reasons for the continuing gap include patient, provider, and health care system factors. Patient-based reasons include failure to recognize the symptoms, underestimating the severity, limited access, reluctance to see a mental health care specialist due to stigma, noncompliance with treatment, and lack of health insurance. Provider factors include poor professional school education about depression, limited training in interpersonal skills, stigma, inadequate time to evaluate and treat depression, failure to consider psychotherapeutic approaches, and prescription of inadequate doses of antidepressant medication for inadequate durations. Mental health care systems create barriers to receiving optimal treatment.”(Hirchfeld et al., 1997).

Studies by our own research group in the 1990s had documented low levels of treatment in patients with chronic forms of major depression. For example, Keller et al. (1995) reported that only 26.8% of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. Subsequently, Oquendo et al., 1999, Oquendo et al., 2002 reported that inadequate treatment was common even in a cohort of depressed inpatients with a history of suicide attempts.

More recent work has documented persistent inadequacy of treatment in VA hospitals (Charbonneau et al., 2003). In addition, Weilburg et al. (2003) conducted a retrospective analysis using pharmacy claims made by patients with a primary care physician in a managed care plan at an academic medical center from 1996 through 1999. Adequate antidepressant treatment was defined as prescription of the lowest likely effective dosage of an antidepressant for at least 90 consecutive days. Data for a total of 15,476 records and 1550 patients were available. Overall, 46% of the patients receiving antidepressants received minimally adequate treatment. The rates of adequate treatment were significantly higher among patients whose antidepressant prescriptions were written by both primary care physicians and psychiatrists (61%) than among patients whose antidepressants were prescribed solely by primary care physicians (31%). Patients who had trials of SSRIs had significantly higher rates of treatment adequacy (51%) than those who had trials of tricyclic antidepressants but not SSRIs (27%) or trials with other antidepressants only (24%). They concluded that adequate antidepressant treatment trials were most likely when psychiatrists collaborated with primary care physicians and when SSRIs were used. Other recent evidence from the National Comorbidity Survey-Replication (Kessler et al., 2003) again showed that less than 21% of patients with depression in the community receive minimally adequate treatment.

Perhaps most surprising is a recent report by Rasmussen et al. (2006) from a large, multisite electroconvulsive therapy (ECT) study. Adequacy of antidepressant medication trials was assessed with the Antidepressant Treatment History Form (ATHF). Among patients with nonpsychotic depression, 27% (60/220) had not had an adequate trial of an antidepressant before ECT, and 63% (139/220) had had at least one inadequate trial. Among patients with psychotic depression, 95% (101/106) had not been given an adequate combination of an antidepressant and antipsychotic agent, mostly due to low doses of the latter class. Use of hypnotic agents and anticonvulsants was common. They concluded that, although patients with severe unipolar depression referred for ECT had high rates of psychotropic usage, much of it was inadequate.

The purpose of this report is to determine whether rates of adequate treatment for patients with chronic depression has changed over the past decade as reflected in the baseline treatment history as documented using the ATHF in the subjects who entered a multisite, NIMH-sponsored clinical trial entitled, “Research Evaluating the Value of Augmentation of Medication by Psychotherapy” (REVAMP). In REVAMP, a large sample of chronically depressed patients received 8–12 weeks of open label treatment using a pharmacotherapy algorithm based on The Texas Medication Algorithm Project (Crismon et al., 1999). Patients entered the algorithm, in which the first step was sertraline, based on their history of treatment response. Patients who failed to remit at the end of this phase were then switched to or augmented with another medication and randomized to augmentation with the Cognitive Behavioral System of Psychotherapy (CBASP; McCullough, 2000), Brief Supportive Psychotherapy (Markowitz et al., 2005), or no psychotherapy.

This is a descriptive analysis. We tabulated the treatment histories and examined relationships between prior treatment and baseline clinical and demographic features, e.g., earlier age at onset and longer duration of illness, which might be expected to be associated with higher levels of prior treatment. We also contrasted the adequacy of treatment with results of earlier studies. The null hypothesis was that treatment adequacy would not have increased over the past decade.

Section snippets

Subjects

Eight academic medical centers participated as clinical sites. Recruitment for the study involved outreach to clinicians affiliated with each site as well as advertising in local communities. Thus, subjects were a mix of respondents to advertisement and clinical referrals seen from 2002–2006.

To be included patients were required to have a current major depressive episode, as defined by DSM-IV and assessed on the SCID (First et al., 1994), of at least 4 weeks duration. All subjects must have

Results

Baseline clinical and demographic characteristics are shown in Table 1. This patient cohort presented with marked chronicity. Index episodes of depression had lasted longer than 6 years on average. The mean duration of illness since the first episode of MDD or dysthymic disorder was twenty years. Fifty nine per cent had educations beyond high school, but only 62% were employed. Only 40% were married. Eleven per cent had made suicide attempts. Lifetime number of depressive episodes was 2.22 +/− 

Discussion

In spite of the levels of severity and chronicity of depression in this sample of patients, only one third had ever had a prior adequate trial of antidepressant medication as defined by the ATHF. The only directly comparable result was that of Keller et al. (1995), who reported adequate trials in 27% of patients with chronic depression presenting to a clinical trial. Regrettably, we must conclude that the hypothesis that rates of treatment adequacy for patients presenting for treatmentof

Role of the funding source

The REVAMP study was sponsored by the National Institute of Mental Health. The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest

No conflict declared.

Acknowledgements

Grant numbers and investigators are listed below.

Cornell University (UO1 MH62475)

James H. Kocsis, M.D.(Lead PI); John C. Markowitz, M.D.; Andrew C. Leon, Ph.D.; Richard A. Friedman, M.D.

University of Pittsburgh (UO1 MH61587)

Michael E. Thase, M.D.(Co-Lead PI); Edward S. Friedman, MD.; Robert H. Howland, M.D, Stephen R. Wisniewski, Ph.D.; Jennifer Barkin, M.S.

University of Stony Brook (UO1 MH62546)

Daniel N. Klein, Ph.D.; Dina Vivian, Ph.D.; Frank Dowling, M.D.; Thomas D'Zurilla, Ph.D.

University

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