Melanie M. Biggs

Sequenced treatment alternatives to relieve depression (STAR*D): Rationale and design

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments.

The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation.

BACKGROUND The present study provides additional data on the psychometric properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief 16-item symptom severity rating scale that was derived from the longer form. Both the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and self-report (IDS-SR30; QIDS-SR16) formats. METHOD The patient samples included 544 out-patients with major depressive disorder (MDD) and 402 out-patients with bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses including sensitivity to change with treatment were conducted. RESULTS Internal consistencies (Cronbachs alpha) ranged from 0.81 to 0.94 for all four scales (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad mood, involvement, energy, concentration and self-outlook had the highest item-total correlations among patients with MDD and BD across all four scales. QIDS-SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30, IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change, indicating high concurrent validity for all four scales. High concurrent validity was also documented based on the SF-12 Mental Health Summary score for the population divided in quintiles based on their IDS or QIDS score. CONCLUSION The QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly acceptable psychometric properties and are treatment sensitive measures of symptom severity in depression.

Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report

OBJECTIVE About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. METHOD A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression. RESULTS In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options. CONCLUSIONS Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

ECT remission rates in psychotic versus nonpsychotic depressed patients: a report from CORE.

Objective To compare the relative efficacy of electroconvulsive therapy (ECT) in psychotic and nonpsychotic patients with unipolar major depression. Methods The outcome of an acute ECT course in 253 patients with nonpsychotic (n = 176) and psychotic (n = 77) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses. ECT was administered with bilateral electrode placement at 50% above the titrated seizure threshold. The remission criteria were rigorous: a score ≤10 on the 24-item Hamilton Rating Scale for Depression (HRSD) after 2 consecutive treatments, and a decrease of at least 60% from baseline. Results The overall remission rate was 87% for study completers. Among these, patients with psychotic depression had a remission rate of 95% and those with nonpsychotic depression, 83%. Improvement in symptomatology, measured by the HRSD, was more robust and appeared sooner in the psychotic patients compared with the nonpsychotic patients. Conclusion Bilateral ECT is effective in relieving severe major depression. Remission rates are higher and occur earlier in psychotic depressed patients than in nonpsychotic depressed patients. These data support the argument that psychotic depression is a distinguishable nosological entity that warrants separate treatment algorithms.

An Evaluation of the Quick Inventory of Depressive Symptomatology and the Hamilton Rating Scale for Depression: A Sequenced Treatment Alternatives to Relieve Depression Trial Report

BACKGROUND Nine DSM-IV-TR criterion symptom domains are evaluated to diagnose major depressive disorder (MDD). The Quick Inventory of Depressive Symptomatology (QIDS) provides an efficient assessment of these domains and is available as a clinician rating (QIDS-C16), a self-report (QIDS-SR16), and in an automated, interactive voice response (IVR) (QIDS-IVR16) telephone system. This report compares the performance of these three versions of the QIDS and the 17-item Hamilton Rating Scale for Depression (HRSD17). METHODS Data were acquired at baseline and exit from the first treatment step (citalopram) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Outpatients with nonpsychotic MDD who completed all four ratings within +/-2 days were identified from the first 1500 STAR*D subjects. Both item response theory and classical test theory analyses were conducted. RESULTS The three methods for obtaining QIDS data produced consistent findings regarding relationships between the nine symptom domains and overall depression, demonstrating interchangeability among the three methods. The HRSD17, while generally satisfactory, rarely utilized the full range of item scores, and evidence suggested multidimensional measurement properties. CONCLUSIONS In nonpsychotic MDD outpatients without overt cognitive impairment, clinician assessment of depression severity using either the QIDS-C16 or HRSD17 may be successfully replaced by either the self-report or IVR version of the QIDS.

Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D.

BACKGROUND Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features. OBJECTIVE The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns. METHOD Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/ Somatization factor score of > or =7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C30). RESULTS The prevalence of anxious depression in this population was 46 %. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features. CONCLUSION This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression).

What Clinical and Symptom Features and Comorbid Disorders Characterize Outpatients with Anxious Major Depressive Disorder: A Replication and Extension:

Objective: We previously found that 46% of the first 1450 outpatients with depression participating in the multicentre Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project qualified for the designation of anxious depression. This study was designed to replicate and extend our initial findings in a subsequent, larger cohort of outpatient STAR*D participants with nonpsychotic major depressive disorder (MDD). Methods: Baseline clinical and sociodemographic data were collected on 2337 consecutive STAR*D participants. A baseline 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor score of 7 or higher was designated as anxious depression. We identified concurrent Axis I disorders with the Psychiatric Diagnostic Screening Questionnaire (PDSQ), using a 90% specificity threshold. Depressive symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30). Results: The prevalence of anxious depression in this population was 45.1%. Patients with anxious MDD were significantly more likely to be in primary care settings and to be women, nonsingle, unemployed, Hispanic, less educated, and suffering from severe depression, both before and after adjustment for overall depression severity. Patients with anxious depression were significantly more likely to meet PDSQ thresholds for generalized anxiety disorder, panic disorder, obsessive–compulsive disorder, posttraumatic stress disorder, agoraphobia, hypochondriasis, and somatoform disorder, both before and after adjusting for baseline depression severity. Individuals with anxious depression were also significantly less likely to endorse IDS-C30 items concerning atypical features and were significantly more likely to endorse items concerning melancholic-endogenous depression features, both before and after adjusting for baseline depression severity. Conclusions: This study clearly replicates our previous STAR*D findings and supports the notion that anxious depression may be a valid diagnostic subtype of MDD, with distinct psychiatric comorbidities and clinical and sociodemographic features.

Brief Psychiatric Rating Scale Expanded Version: How do new items affect factor structure?

Our goal was to suggest a factor structure for the Brief Psychiatric Rating Scale Expanded Version (BPRS-E) based upon a large and diverse sample and to determine which of the new items improved the factors derived from the 18-item version of the scale that have been used in clinical research for decades. We investigated the consistency of our proposed model over time and across demographic groups. As part of the Texas Medication Algorithm Project, the BPRS-E was administered to a total of 1440 psychiatric outpatients in three different diagnostic groups on multiple occasions. The sample was randomly split so that exploratory factor analysis could be done with the first half, and the model could be confirmed on the second half. A four-factor structure including factors assessing depression/anxiety, psychosis, negative symptoms, and activation was found. For each factor, we specify items in the expanded version that added to the breadth of the commonly used clinical factors while improving or maintaining goodness of fit and reliability. The final model proposed was consistent over time and across diagnosis, phase of illness, age, gender, ethnicity, and level of education. The BPRS-E has a stable four-factor structure, making it useful as a clinical outcome measure.

Polysomnographic parameters in first-degree relatives of unipolar probands

We present polysomnographic data for psychiatrically asymptomatic first-degree relatives of unipolar depressed probands. Relatives were classified by proband rapid eye movement (REM) latency (reduced/nonreduced) and by personal REM latency (reduced/nonreduced). Reduced REM latency relatives, whether defined by the proband or by their own REM latency, had polysomnographic alterations consistent with those found in depressed patients, although none of these relatives was depressed at assessment. Reduced REM latency relatives with a history of unipolar depression were compared to reduced REM latency relatives with no history of depression. Virtually no polysomnographic differences were found. Polysomnographic alterations may be stable antecedents of the onset of depression.

One-year clinical outcomes of depressed public sector outpatients: a benchmark for subsequent studies

BACKGROUND The symptomatic outcomes of a cohort of public mental health sector depressed outpatients treated for 1 year are described to provide a benchmark for future long-term trials. Baseline moderators of outcome were evaluated. METHODS Outpatients with nonpsychotic major depressive disorder (n = 118) scoring >/=30 on the 30-item Inventory of Depressive Symptomatology-Clinician Rating (IDS-C(30)) were treated with a medication algorithm and patient/family education package. Response and remission rates were assessed every 3 months with the IDS-C(30). Logistic regression analyses evaluated several baseline features in relation to outcome. RESULTS While response and remission rates increased from 3 to 12 months, the 1-year last observation carried forward (LOCF) response (26.3%) and remission (11.0%) rates were not impressive (sustained response = 14.4%; sustained remission = 5.1%). Younger patients and those with full-time employment (at baseline) were more likely to respond. A shorter length of illness tended to be associated with higher response and remission rates (p <.10). Results are generalizable to public sector patients with substantial socioeconomic, general medical, and educational disadvantages who were sufficiently depressed to recommend a change in antidepressant medication. CONCLUSIONS Response and remission rates were modest when compared with outcomes in shorter duration efficacy trials in depressed outpatients with less chronicity, fewer concurrent general medical conditions, and less treatment resistance. Results support the need for more powerful treatments and/or the better delivery of available treatments.