Philip T. Ninan

The 16-Item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression

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) (Cronbachs alpha =.86), the IDS-SR(30) (Cronbachs alpha =.92), and the HAM-D(24) (Cronbachs 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.

Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma

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.

Report by the ACNP Task Force on Response and Remission in Major Depressive Disorder

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: A naturalistic study

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.

A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression

BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual (VNS+TAU) during open trials of patients with treatment-resistant depression (TRD). To better understand these effects on long-term outcome, we compared 12-month VNS+TAU outcomes with those of a comparable TRD group. METHODS Admission criteria were similar for those receiving VNS+TAU (n = 205) or only TAU (n = 124). In the primary analysis, repeated-measures linear regression was used to compare the VNS+TAU group (monthly data) with the TAU group (quarterly data) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR(30)). RESULTS The two groups had similar baseline demographic data, psychiatric and treatment histories, and degrees of treatment resistance, except that more TAU participants had at least 10 prior major depressive episodes, and the VNS+TAU group had more electroconvulsive therapy before study entry. Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30) than TAU across 12 months (p < .001). Response rates according to the 24-item Hamilton Rating Scale for Depression (last observation carried forward) at 12 months were 27% for VNS+TAU and 13% for TAU (p < .011). Both groups received similar TAU (drugs and electroconvulsive therapy) during follow-up. CONCLUSIONS This comparison of two similar but nonrandomized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months.

Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination.

BACKGROUND Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients. METHODS Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health. RESULTS Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alones effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point. CONCLUSIONS Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.

Does cytokine-induced depression differ from idiopathic major depression in medically healthy individuals?

BACKGROUND Cytokines of the innate immune response may contribute to behavioral alterations that resemble major depression as manifested in medically healthy individuals. METHODS To explore potential similarities and differences between cytokine-induced depression and idiopathic major depression in healthy subjects, dimensional analyses comparing specific symptom dimensions of depression were conducted in 20 patients with malignant melanoma administered the innate immune cytokine, interferon (IFN)-alpha, and 28 medically healthy subjects with major depression of similar age and gender distribution. The Hamilton Rating Scale for Depression was used to assess severity of individual depressive symptoms. RESULTS Severity of symptoms of anxiety, depressed mood, and impaired work/activities were comparable between patients with IFN-alpha-induced depression and medically healthy depressed patients. Interestingly, however, compared to medically healthy patients with major depression, patients with IFN-alpha-induced depression reported significantly greater psychomotor retardation and weight loss and significantly less severe feelings of guilt. LIMITATIONS The relatively small sample size limited statistical power to detect small differences in symptom expression among groups. CONCLUSIONS The data suggest that there is considerable overlap in symptom expression between cytokine-induced depression and idiopathic depression in medically healthy subjects. Nevertheless, differences in isolated symptom domains suggest that cytokines may preferentially target neurocircuits relevant to psychomotor activity (e.g. basal ganglia), while having a limited effect on cognitive distortions regarding self-appraisal.

Sertraline in the treatment of rape victims with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a significant problem following rape, yet reports on the efficacy of pharmacological agents in this population are lacking. The results of an open 12-week clinical trial utilizing sertraline (mean dose 105 mg) in the treatment of adult female rape victims with chronic PTSD are presented. The five completers were, on average, 41.6 years old and 15.6 years postassault. Sertraline reduced PTSD and related symptoms in these rape victims. The mean Clinician Administered PTSD Scale (CAPS) scores decreased by 53%, with four out of five participants responding positively to treatment. These preliminary results support the need for systematic assessment of sertraline in this population.

Cytochrome P450 2D6 phenotype predicts antidepressant efficacy of venlafaxine: a secondary analysis of 4 studies in major depressive disorder.

INTRODUCTION Venlafaxine, a serotonin-norepinephrine reuptake inhibitor antidepressant, is metabolized primarily by the cytochrome P450 2D6 enzyme into O-desmethylvenlafaxine (ODV). The ODV/venlafaxine ratio can be used to distinguish between extensive metabolizers (EMs) and poor metabolizers (PMs). OBJECTIVES To determine the relative efficacy and tolerability of venlafaxine in EM vs PM patients with major depressive disorder (MDD). METHOD Data from 4 double-blind, placebo-controlled studies of patients with MDD were pooled. Blood samples were analyzed for plasma concentrations of venlafaxine, ODV, total venlafaxine + ODV, and ODV/venlafaxine ratio. Patients were classified as EMs or PMs on the basis of ODV/venlafaxine ratios. Changes from baseline in depression scale scores were compared between EMs and PMs using t tests. Rates of response, remission, discontinuation, and adverse events (AEs) were compared for EMs and PMs using Fisher exact tests. RESULTS Compared with PMs, EMs had significantly greater mean changes from baseline on 4 of 5 depression rating scales (all 4 comparisons, P ≤ .020). A significantly greater percentage of EMs achieved response or remission by most measures compared with PMs (4 of 5 comparisons, P ≤ .015). Rates of discontinuation and AEs did not differ significantly between EMs and PMs. Since there were no substantial differences between EMs and PMs in terms of venlafaxine dose or tolerability, these factors are not likely to account for the efficacy findings. CONCLUSIONS Venlafaxine treatment in EMs was associated with greater efficacy in MDD on virtually all measures compared with PMs, with no important tolerability differences.

Placebo-controlled study of fluvoxamine in the treatment of patients with compulsive buying.

Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.