Faculty Bibliography

BACKGROUND:The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS:This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS:The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS:These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.

Panic disorder entered the psychiatric nomenclature a quarter-century ago, and an explosion of studies followed. Defining the core phenomenology of panic disorder can be advanced by an understanding of its pathophysiology and exploration of its etiology. The lessons learned can guide the delivery of treatments to enhance the likelihood of achieving remission and the discovery of novel treatments for panic disorder.

BACKGROUND:Benefit from selective serotonin reuptake inhibitor (SSRI) treatment in major depressive disorder (MDD) usually takes several weeks. Typically, a third of patients achieve remission and roughly half achieve response with acute treatment. This open-label study evaluated the efficacy and safety of modafinil treatment initiated with an SSRI in patients with MDD and fatigue. METHOD/METHODS:Twenty-nine patients with DSM-IV MDD, free from antidepressant therapy (> or = 4 weeks), were administered modafinil (titrated to 200 mg/day) and fluoxetine or paroxetine (20 mg/day) for 6 weeks. Assessments included the 21-item Hamilton Rating Scale for Depression (HAM-D), Structured Interview Guide for the HAM-D (SIGH-D), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS). The SIGH-D ratings were videotaped and rated by an independent rater masked to the visit schedule. Data were collected from August 2002 through March 2003. RESULTS:Modafinil combined with an SSRI at treatment initiation significantly improved mean total SIGH-D scores within 1 week (-9.3, p <.001), and this improvement was progressive throughout the study (-21.2 at week 6, p <.001). Forty-two percent (11 of 26) and 79% (19 of 24) of patients were responders, and 39% (10 of 26) and 58% (14 of 24) of patients were remitters (HAM-D) by week 2 and week 6, respectively. Adjunct modafinil rapidly and significantly reduced fatigue (FSS score reduction from baseline = 0.7 at week 1, p <.01) and improved wakefulness (ESS score reduction from baseline = 3.6 at week 1, p <.01). The combination caused few adverse events, with nausea and headache being the most common. CONCLUSION/CONCLUSIONS:Modafinil combined with an SSRI at treatment initiation may enhance the onset and degree of symptom benefit in patients with MDD and fatigue. Treatment with adjunct modafinil was generally well tolerated, with most adverse effects being mild or moderate in severity.

OBJECTIVE:The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD). METHOD/METHODS:253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted. RESULTS:Fluvoxamine CR was significantly (p <.05) superior to placebo in decreasing YBOCS total score beginning at week 2. This early response was sustained at all subsequent visits. At endpoint, there was a mean decrease of 8.5 +/- 0.7 (31.7%) in the YBOCS total score compared with baseline in the fluvoxamine CR treatment group versus a mean decrease of 5.6 +/- 0.7 (21.2%) in the placebo group (p =.001). Fluvoxamine CR was also significantly superior to placebo in lowering the severity of illness (CGI-S, p =.002) and in producing clinical improvement (CGI-I, p <.01). At endpoint, significantly greater percentages of the fluvoxamine CR treatment group were responders (p =.002) and remitters (p =.019) compared with the placebo group. CONCLUSION/CONCLUSIONS:Over 12 weeks, fluvoxamine CR treatment was associated with a statistically significant and clinically relevant reduction in OCD severity and was found to be safe and well tolerated. The early onset of therapeutic effect, starting from week 2, was of particular interest.

The 16-item Quick Inventory of Depressive Symptomatology (QIDS), a new measure of depressive symptom severity derived from the 30-item Inventory of Depressive Symptomatology (IDS), is available in both self-report (QIDS-SR(16)) and clinician-rated (QIDS-C(16)) formats. This report evaluates and compares the psychometric properties of the QIDS-SR(16) in relation to the IDS-SR(30) and the 24-item Hamilton Rating Scale for Depression (HAM-D(24)) in 596 adult outpatients treated for chronic nonpsychotic, major depressive disorder. Internal consistency was high for the QIDS-SR(16) (Cronbach's alpha =.86), the IDS-SR(30) (Cronbach's alpha =.92), and the HAM-D(24) (Cronbach's alpha =.88). QIDS-SR(16) total scores were highly correlated with IDS-SR(30) (.96) and HAM-D(24) (.86) total scores. Item-total correlations revealed that several similar items were highly correlated with both QIDS-SR(16) and IDS-SR(30) total scores. Roughly 1.3 times the QIDS-SR(16) total score is predictive of the HAM-D(17) (17-item version of the HAM-D) total score. The QIDS-SR(16) was as sensitive to symptom change as the IDS-SR(30) and HAM-D(24), indicating high concurrent validity for all three scales. The QIDS-SR(16) has highly acceptable psychometric properties, which supports the usefulness of this brief rating of depressive symptom severity in both clinical and research settings.

Obsessive-compulsive disorder (OCD) is an anxiety disorder that commonly presents comorbidly with other psychiatric disorders. The underlying neurobiology of OCD is associated with circuits involving the basal ganglia, thalamus, and the frontal cortex. Randomized, placebo-controlled trials indicate acute and long-term efficacy of potent selective serotonin reuptake inhibitors (SSRIs), such as paroxetine. There is suggestive evidence that higher doses of paroxetine than those used in major depression are needed for benefit in OCD. Because of their safety and beneficial adverse-event profile, the SSRIs have become the leading choice in the pharmacological management of OCD.

Major depressive disorder is associated with considerable morbidity, disability, and risk for suicide. Treatments for depression most commonly include antidepressants, psychotherapy, or the combination. Little is known about predictors of treatment response for depression. In this study, 681 patients with chronic forms of major depression were treated with an antidepressant (nefazodone), Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or the combination. Overall, the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment. Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), psychotherapy alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the childhood abuse cohort. Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma.

BACKGROUND:Limited information is available on treatment response of anxiety symptoms in chronic forms of major depression. Concurrent anxiety disorders are prevalent in chronic depression, but the responsiveness of patients with such comorbidity to different treatments is largely unknown. This study investigated the comparative efficacy of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), and their combination in improving anxiety symptoms in patients with chronic forms of major depression, including those with a concurrent anxiety disorder. METHOD/METHODS:681 patients with chronic major depressive disorder (DSM-IV criteria) participated in a multicenter study of 12 weeks of acute treatment with nefazodone (N = 226), CBASP (N = 228), or the combination (N = 227). The Hamilton Rating Scale for Anxiety (HAM-A), the HAM-A psychic anxiety factor, and the anxiety/arousal subscale of the 30-item Inventory for Depressive Symptomatology-Self Report (IDS-SR-30) were used to assess anxiety symptoms. RESULTS:In the full sample. without controlling for change in depressive symptoms, combination therapy was superior to both monotherapies on all 3 anxiety measures both in the rate of change and at endpoint. When change in depressive symptoms was controlled for, there were no treatment differences in rate of change from baseline to week 12 on any of the 3 anxiety measures. In those patients with a concurrent anxiety disorder, however, the combination was superior to CBASP on the HAM-A and the IDS-SR-30. Nefazodone alone and combination therapy were both superior to CBASP on the HAM-A psychic anxiety factor. CONCLUSION/CONCLUSIONS:For patients with chronic depression, combination therapy is superior to CBASP or nefazodone alone. Among patients with a concurrent anxiety disorder, nefazodone. either alone or in combination with CBASP, improves anxiety symptoms faster than CBASP alone, independent of depressive symptom reduction.