Incremental cost-effectiveness of combined therapy vs medication only for youth with selective serotonin reuptake inhibitor-resistant depression: treatment of SSRI-resistant depression in adolescents trial findings.

CONTEXT: Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective. OBJECTIVE: To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI. DESIGN: Randomized controlled trial. SETTING: Six US academic and community clinics. PATIENTS: Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression. INTERVENTION: Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy. MAIN OUTCOME MEASURES: Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs (DFD-QALYs). Costs of intervention, nonprotocol services, and families were included. RESULTS: Combined treatment achieved 8.3 additional DFDs (P = .03), 0.020 more DFD-QALYs (P = .03), and 11.0 more DIDs (P = .04). Combined therapy cost $1633 more (P = .01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER] = $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78,948 per DFD-QALY (ICER = $78,948; 95% CI, -$9261 to $677,448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100,000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions. CONCLUSIONS: For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00018902.

Characteristics and predictors of social phobia course in a longitudinal study of primary-care patients.

BACKGROUND: Social Phobia (SP) is a prevalent disorder in primary-care settings. To date, few researchers have examined the natural course of SP in primary care. We examined the natural course and predictors of recovery in a large sample of primary-care patients. METHODS: Data are obtained from the Primary Care Anxiety Project, a naturalistic, longitudinal study of anxiety disorders in primary-care patients. This report pertains to 182 patients with SP at intake. We examined intake demographic and clinical variables as predictors of recovery within the 5 years of follow-up. RESULTS: The probability of recovery from SP during the 5-year follow-up period was .40. At intake, a longer duration of SP episode, comorbid Panic Disorder with Agoraphobia, and lower psychosocial functioning predicted lower rates of recovery. CONCLUSIONS: These findings highlight the chronicity of SP, as well as factors that may affect its naturalistic course. It is imperative that primary-care physicians and mental health specialists assess for and treat SP in their practices. Future research is warranted to further examine the effect of medical and psychiatric comorbidity on SP course.

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

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.

Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression-polarity (SAD-P).

BACKGROUND: Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depression. The goal of this study was to develop and validate a brief instrument to screen for bipolar disorder in patients actively ill with major depression. METHOD: The sample consisted of subjects who enrolled in the National Institute of Mental Health-Collaborative Program on the Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode of major depression and included 91 subjects with bipolar I major depression, 52 with bipolar II major depression, and 338 with unipolar major depression diagnosed according to Research Diagnostic Criteria. Most of the subjects were inpatients at the time of enrollment, and subjects were prospectively followed for up to 20 years. In order to create, test, and cross-validate the screening instrument, a split-sample data analytic procedure was performed. This procedure yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross-validation sample, and the bipolar II cross-validation sample. Each group included subjects with bipolar major depression and subjects with unipolar major depression. Within the bipolar I index sample, subjects with bipolar I major depression at study intake were compared with subjects with unipolar major depression at study intake on a pool of 59 sociodemographic and clinical candidate variables. The 3 variables showing the greatest disparity between bipolar I subjects and unipolar subjects were selected for the screen, the Screening Assessment of Depression-Polarity (SAD-P). The operating characteristics of the SAD-P were then examined within the bipolar I index sample, bipolar I cross-validation sample, and bipolar II cross-validation sample. RESULTS: The items selected for the screening instrument were (1) presence of delusions during the current episode of major depression, (2) number of prior episodes of major depression, and (3) family history of major depression or mania. The screen identified bipolar major depression with a sensitivity of 0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation sample, and 0.58 in the bipolar II cross-validation sample. With regard to misclassifying subjects with unipolar major depression, the screen provided a positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation sample. CONCLUSION: We suggest using the 3-item SAD-P as a preliminary screen for bipolar disorder in patients who present with an active episode of major depression.

Prevalence and impact of comorbid anxiety and bipolar disorder.

Comorbid conditions pose a serious risk to patients with bipolar disorder, but anxiety comorbidity poses a specific hazard due to the increased negative impact of anxiety on illness course and treatment. Anxiety comorbidity appears to be highly prevalent and is associated with intensified symptoms of bipolar disorder and additional comorbid disorders, resulting in a negative impact on the patient and on the course of the illness. The presence of anxiety in bipolar patients is also associated with a lowered age at onset, hampered patient response to treatment such as lithium, increased rates of suicide and substance abuse, and decreased quality of life. Patients can experience work, family, and social impairment and be made to contend with increased health care costs and strains on family support. Studies are few and have a limited scope, and many have failed to consider the clinical significance of comorbid anxiety and bipolar disorder. Because the degree to which anxiety impacts patients with bipolar disorder is not fully known, more information is needed about the relationship between bipolar disorder and anxiety.

Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study.

CONTEXT: Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder (BP-I) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder (BP-II). OBJECTIVE: To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II. DESIGN: A naturalistic study with 20 years of prospective, systematic follow-up. SETTING: Inpatient and outpatient treatment facilities at 5 US academic centers. Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean (SD) of 15 (4.8) years in the National Institute of Mental Health Collaborative Depression Study. MAIN OUTCOME MEASURES: The relationship, by random regression, between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews. RESULTS: Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II, and they may even enhance functioning. Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and, in some cases, significantly more so. At each level of depressive symptom severity, BP-I and BP-II are equally impairing. When asymptomatic, patients with bipolar disorder have good psychosocial functioning, although it is not as good as that of well controls. CONCLUSIONS: Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II. Important findings for clinical management are the following: (1) depressive episodes and symptoms, which dominate the course of BP-I and BP-II, are equal to or more disabling than corresponding levels of manic or hypomanic symptoms; (2) subsyndromal depressive symptoms, but not subsyndromal manic or hypomanic symptoms, are associated with significant impairment; and (3) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II.

Issues in treatment-resistant depression.

Major depressive disorder is a debilitating disease that imposes significant social and economic burdens not only on patients but also on society. Although various treatment options are available, treatment-resistant depression is common. Determining the exact prevalence of treatment-resistant depression is difficult because definitions vary, as do definitions of antidepressant response. Operational definitions of antidepressant response, nonresponse, partial response, and remission will be discussed in this article. Pharmacotherapy options for patients with treatment-resistant depression include augmentation, combination, and switching therapies; however, data from controlled clinical trials supporting these therapies are limited. Electroconvulsive therapy and psychotherapy offer additional treatment strategies. New nonpharmacologic therapies are under investigation. Remission is the goal of treatment.

Mental health treatment received by primary care patients with posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is receiving growing attention as a pervasive and impairing disorder but is still undertreated. Our purpose was to describe the characteristics of mental health treatment received by primary care patients diagnosed with PTSD. METHOD: 4383 patients from 15 primary care, family practice, or internal medicine clinics were screened for anxiety symptoms using a self-report questionnaire developed for the study. Those found positive for anxiety symptoms (N = 539) were interviewed with the Structured Clinical Interview for DSM-IV. Of these patients, 197 met diagnostic criteria for PTSD and were examined in the present study regarding the rates and types of mental health treatment they were currently receiving. Data were gathered from July 1997 to May 2001. RESULTS: Nearly half (48%) of the patients in general medical practice with PTSD were receiving no mental health treatment at the time of intake to the study. Of those receiving treatment, psychopharmacologic interventions were most common. Few patients were receiving empirically supported psychosocial interventions. Current comorbid major depressive disorder and current comorbid panic disorder with agoraphobia were significantly associated with receiving mental health treatment (major depressive disorder, p <.10; panic disorder with agoraphobia, p <.05). The most common reason patients gave for not receiving medication was the failure of physicians to recommend such treatment, which was also among the most common reasons for not receiving psychosocial treatment. CONCLUSIONS: Despite the morbidity, psychosocial impairment, and distress associated with PTSD, substantial proportions of primary care patients with the disorder are going untreated or are receiving inadequate treatment. Results suggest a need for better identification and treatment of PTSD in the primary care setting.

Nonpsychiatric illness among primary care patients with trauma histories and posttraumatic stress disorder.

OBJECTIVE: The authors examined the relationship between posttraumatic stress disorder (PTSD), trauma, and self-reported nonpsychiatric medical conditions in a sample of 502 primary care patients with one or more anxiety disorders. METHODS: Primary care patients with one or more DSM-IV anxiety disorders were assessed for comorbid psychiatric and substance use problems and for a history of trauma. These individuals also completed a self-report measure of current and lifetime medical conditions, lifetime tobacco use, and current regular exercise. RESULTS: Of 502 participants with at least one anxiety disorder, 84 (17 percent) reported no history of trauma, 233 (46 percent) had a history of trauma but no PTSD, and 185 (37 percent) met DSM-IV criteria for PTSD. Patients with PTSD reported a significantly greater number of current and lifetime medical conditions than did participants with other anxiety disorders but without PTSD. Primary care patients with PTSD were more likely to have had a number of specific medical problems, including anemia, arthritis, asthma, back pain, diabetes, eczema, kidney disease, lung disease, and ulcer. Possible explanations for the greater rates of medical conditions among participants with PTSD were examined as predictors in multiple regression. PTSD was found to be a stronger predictor of reported number of medical problems than trauma history, physical injury, lifestyle factors, or comorbid depression. CONCLUSIONS: These findings suggest that PTSD is associated with a higher rate of general medical complaints.