Cognitive behavioral therapy for depressed adolescents exposed to interpersonal trauma: an initial effectiveness trial.

Four clinical trials have shown that a history of interpersonal trauma is associated with diminished response to cognitive-behavioral therapy (CBT) for adolescent depression. An efficacious CBT protocol for adolescent depression was modified to address cognitive deficits and distortions associated with interpersonal trauma. Initial feasibility, acceptability, and treatment impact of the modified treatment (m-CBT) were evaluated in a randomized effectiveness trial conducted in community clinics. Clients were 43 referred adolescents with a depressive disorder and a history of interpersonal trauma. Adolescents either received m-CBT or usual care (UC) therapy. Results indicated that m-CBT was delivered with good fidelity by community clinicians, but that number of sessions completed was attenuated in both m-CBT and UC. Adolescents reported high levels of treatment satisfaction and acceptability for the new treatment. There were significant reductions in depressive symptoms over time, but no differences in outcomes between groups. Although the new treatment produced promising results, it did not outperform UC. Implications for treatment development are considered.

The effects of continuous antidepressant treatment during the first 6 months on relapse or recurrence of depression.

BACKGROUND: To examine whether continuous antidepressant treatment during the first 6 month reduces the risk of relapse/recurrence of depression in South Korea. METHODS: We used National Health Insurance Data covering the period from 2001 through 2004. The study population consisted of 117,087 adult patients who received antidepressants after being diagnosed with depression. The continuous antidepressant was defined as evidence of antidepressant prescriptions for 75% of the first 6 months of treatment. Relapse or recurrence during the next 18-month period was defined by evidence of a new episode requiring antidepressant treatment, psychiatric hospitalization, electroconvulsive therapy, emergency department visit or attempted suicide. We compared the relapse/recurrence rate during the 18-month follow-up period in patients receiving continuous treatment and those who discontinued early using a Cox's proportional hazard model. RESULTS: Patients receiving continuous antidepressant treatment experienced a lower risk of relapse/recurrence (Hazard ratio: 0.42, 95% CI: 0.40-0.44). Three or more follow-up visits in the first 3 months also reduced the risk of relapse/recurrence. Factors associated with a significant increase of relapse/recurrence were comorbid medical illness, anxiety disorder, and alcohol abuse. The small benefit of SSRIs was appeared only in the early discontinued treatment subgroup, not in the continuous treatment subgroup. LIMITATIONS: We were not able to consider the antidepressant utilization pattern. CONCLUSIONS: Continuous antidepressant treatment and frequent follow-up visits during the acute phase were associated with a significant reduction in the likelihood of relapse or recurrence of depression. Our results provide important evidence on the effectiveness of antidepressant treatment in South Korea.

Cognitive-behavioral therapy for suicide prevention (CBT-SP): treatment model, feasibility, and acceptability.

OBJECTIVE: To describe the elements of a manual-based cognitive-behavioral therapy for suicide prevention (CBT-SP) and to report its feasibility in preventing the recurrence of suicidal behavior in adolescents who have recently attempted suicide. METHOD: The CBT-SP was developed using a risk reduction and relapse prevention approach and theoretically grounded in principles of cognitive-behavioral therapy, dialectical behavioral therapy, and targeted therapies for suicidal youths with depression. The CBT-SP consists of acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, skill building, psychoeducation, family intervention, and relapse prevention. RESULTS: The CBT-SP was administered to 110 recent suicide attempters with depression aged 13 to 19 years (mean 15.8 years, SD 1.6) across five academic sites. Twelve or more sessions were completed by 72.4% of the sample. CONCLUSIONS: A specific intervention for adolescents at high risk for repeated suicide attempts has been developed and manual based, and further testing of its efficacy seems feasible.

Self-management practices among primary care patients with musculoskeletal pain and depression.

The objective of this study was to assess the effect of clinical depression on pain self-management practices. We employed a cross-sectional analysis of baseline data from the Stepped Care for Affective disorders and Musculoskeletal Pain (SCAMP) study. Participants included 250 patients with pain and comorbid depression and 250 patients with pain only and were enrolled from urban university and VA primary care clinics. Musculoskeletal pain was defined as low back, hip or knee pain present >or=3 months and with at least a moderate, Brief Pain Inventory severity score >or=5. Depression was defined as a PHQ-9 score >or=10. We used multiple logistic and Poisson regression to assess the relationship between individual and combined effects of depression and pain severity on two core pain self-management skills: exercise duration and cognitive strategies. Depressed patients exercised less per week than did nondepressed patients but showed a trend towards more frequent use of cognitive strategies. On multivariable analysis, depression severity substantially decreased the use of exercise as a pain self-management strategy. In contrast, depression and pain severity interacted to increase the use of cognitive strategies. Depression and pain severity have differential effects on self-management practices. Understanding the differences between preferential strategies of pain patients with and without depression may be useful in tailoring pain self-management programs.

The historical roots of the "bipolar spectrum": did Aristotle anticipate Kraepelin's broad concept of manic-depression?

The construct of bipolar disorder, or bipolar spectrum disorders, has been a source of controversy in recent years. Some have argued that subtle variants within the putative bipolar spectrum are merely the creation of overzealous clinicians, perhaps encouraged by various special interest groups. In reality, the concept of a bipolar spectrum may be inferred from numerous classical sources, dating back to the 19th century and even into antiquity. The Greek philosopher Aristotle, usually considered the author of a work called Problemata, appears to have recognized some form of the bipolar spectrum, more than two millennia ago. This recognition continues throughout the 19th century, and into our own time. Such transcultural findings across many centuries have implications for the "objective" nature of psychiatric disease.

Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS.

OBJECTIVE: Subsyndromal major depressive disorder is common among HIV-positive adults. This study was designed to assess the efficacy of dehydroepiandrosterone (DHEA) as a potential treatment. METHOD: One hundred forty-five patients with subsyndromal depression or dysthymia were randomly assigned to receive either DHEA or placebo; 90% (69 of 77) of the DHEA patients and 94% (64 of 68) of the placebo patients completed the 8-week trial. The primary measure of efficacy was a Clinical Global Impression improvement rating of 1 or 2 (much or very much improved) plus a final Hamilton Depression Rating Scale score

Affect-modulated startle in adults with childhood-onset depression: relations to bipolar course and number of lifetime depressive episodes.

To study affect regulation in adults with unipolar (n=38) and bipolar (n=38) forms of childhood-onset depression (COD), as compared with adults with no history of psychiatric illness (n=60), we examined affective modulation of the startle eyeblink reflex. Participants were subjected to binaural bursts of white noise while viewing pictures designed to elicit pleasant, neutral, or unpleasant affective states. The blink response was recorded from surface electrodes over the orbicularis oculi muscle during and following pictures. Participants rated the valence and arousal of their responses. Unlike control or bipolar groups, the unipolar group displayed a greater startle during the neutral condition than during the pleasant condition, and failed to display an increase in startle during the unpleasant condition. The bipolar group, unlike the unipolar and control groups, displayed a similar startle response after pleasant and unpleasant pictures. Participants with a high number of lifetime depressive episodes displayed a blunted startle response across affective conditions. Groups reported similar subjective responses to affective stimuli. Current affective symptoms and comorbid diagnoses did not influence startle modulation. In unipolar and bipolar forms of COD, unusual affective modulation or maintenance of the startle response, respectively, may reflect underlying deficits in affect regulation.

Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients.

BACKGROUND: Dysthymic disorder is a relatively common illness that is often treated with antidepressants. Compared with the study of major depression, there has been little systematic study of potentiation strategies for antidepressant-refractory dysthymic disorder. METHOD: Following a patient's report of dramatic response to the addition of chromium supplementation to sertraline pharmacotherapy for dysthymic disorder (DSM-IV), the authors initiated a series of single-blind and open-label trials of chromium picolinate or chromium polynicotinate in the treatment of antidepressant-refractory dysthymic disorder. RESULTS: In a series of 5 patients, chromium supplementation led to remission of dysthymic symptoms. Single-blind substitution of other dietary supplements in each of the patients demonstrated specificity of response to chromium supplementation. CONCLUSION: Preliminary observations suggest that chromium may potentiate antidepressant pharmacotherapy for dysthymic disorder. Controlled studies are indicated to test the validity of these initial observations.

Massage and music therapies attenuate frontal EEG asymmetry in depressed adolescents.

EEG asymmetry, specifically greater relative right frontal activation, is associated with negative affect. Depressed adults show stable patterns of this asymmetry. The present study assessed the effects of massage therapy and music therapy on frontal EEG asymmetry in depressed adolescents. Thirty adolescents with greater relative right frontal EEG activation and symptoms of depression were given either massage therapy (n = 14) or music therapy (n = 16). EEG was recorded for three-minute periods before, during, and after therapy. Frontal EEG asymmetry was significantly attenuated during and after the massage and music sessions.

The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies.

BACKGROUND: Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. METHOD: We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). RESULTS: Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. CONCLUSION: Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features.

OBJECTIVE: Inconsistent results have been reported concerning circulating lymphocyte subsets in depression. To establish whether the immune alterations in depression could be related to neurovegetative symptoms, lymphocyte subsets were assessed in major depressive and dysthymic patients who exhibited either typical or atypical features (ie, the latter characterized by mood reactivity and reversed neurovegetative features). METHOD: Blood was collected from major depressive, atypical depressive, typical dysthymic, or atypical dysthymic patients and from nondepressed control subjects. Circulating lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/CD56) were determined by flow cytometry. In a subset of patients, lymphocyte subsets were also determined after a 12-week course of antidepressant medication. RESULTS: Although T and B cell populations did not differ between the depressive subtypes and control subjects, circulating natural killer (NK) cells were elevated in depressive illness, and varied as a function of depressive subtype and sex. Among male patients, NK cells were elevated to a greater extent in typical than in atypical depression, and more so in major depressive than in dysthymic patients. Among female patients, circulating NK cells were lower than in male patients, and only among the typical major depressive patients did NK cells exceed those of controls. Normalization of NK cells occurred with successful pharmacotherapy. CONCLUSIONS: Depression may be associated with elevated levels of circulating NK cells. Although the neurovegetative features associated with depression, particularly altered eating, may have contributed to the elevated NK cells, depressive affect itself also contributed in this respect. However, the relative contributions of these factors varied between male and female patients.

Increased serum interleukin-1-receptor-antagonist concentrations in major depression.

Recently, it has been shown that major depression may be accompanied by an increased production of interleukin-1 beta (IL-1 beta), an acute phase (AP) response and simultaneous signs of activation and suppression of cell-mediated immunity. The interleukin-1-receptor antagonist (IL-1-rA) is released in vivo during an AP response and serum levels are increased in many immune disorders. The release of IL-1-rA may limit the pro-inflammatory effects of IL-1. This study has been carried out to examine serum IL-1-Ra in 68 depressed subjects (21 minor, 25 simple major and 22 melancholic subjects) vs. 22 normal controls. Depressed subjects showed significantly higher serum IL-1-rA concentrations than healthy controls. 29% of all depressed subjects had serum IL-1-rA levels higher than the mean value +2 standard deviations of normal controls; 44% depressed subjects had IL-1-rA values greater than 0.215 ng/ml with a specificity of 90%. In depressed subjects, there was a significant and positive relationship between serum IL-1-rA and severity of illness. In depression, there were no significant relationships between serum IL-1-rA concentrations and indicants of hypothalamic-pituitary-adrenal (HPA)-axis activity, such as 24-h urinary cortisol and postdexamethasone cortisol values. Women had significantly higher serum IL-1-rA levels than men. The findings support the thesis that depression is accompanied by an immune-inflammatory response.