Depression-free days as a summary measure of the temporal pattern of response and remission in the treatment of major depression: a comparison of venlafaxine, selective serotonin reuptake inhibitors, and placebo.

Background: This article develops and applies depression-free days (DFDs) as a summary measure of the temporal pattern of response and remission in a comparison of venlafaxine (a dual-action serotonin-norepinephrine reuptake inhibitor) with selective serotonin reuptake inhibitors (SSRIs) and placebo.

Method: Weekly data on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) from 2046 patients with DSM-III-R/IV-established moderate-to-severe major depression, participating in 1 of 8 randomized, double-blind, controlled studies that compared venlafaxine with an SSRI (fluoxetine, paroxetine, or fluvoxamine) or with both placebo and an SSRI, were used to estimate DFDs. Maximum DFDs were imputed to maintained HAM-D-17 scores < or = 7 (asymptomatic depression) over time, minimum DFDs to persistent HAM-D-17 scores > or = 15 (acutely symptomatic depression), and prorated DFDs to intermediate HAM-D-17 scores.

Onset of major depression during treatment for nicotine dependence.

We monitored the emergence of major depression (MDD) during treatment for nicotine dependence among 224 smokers. MDD was assessed on three occasions during the course of treatment with the mood disorders portion of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID), fourth edition (DSM-IV). Out of 224 participants, 20% had suffered a past episode of MDD, 18% of males and 22% of females.

Regional analysis of hippocampal activation during memory encoding and retrieval: fMRI study.

Investigators have recently begun to examine the differential role of subregions of the hippocampus in episodic memory. Two distinct models have gained prominence in the field. One model, outlined by Moser and Moser (Hippocampus 1998;8:608-619), based mainly on animal studies, has proposed that episodic memory is subserved by the posterior two-thirds of the hippocampus alone.

Neuroendocrine aspects of hypercortisolism in major depression.

A consistent finding in biological psychiatry is that hypothalamic-pituitary-adrenal (HPA) axis physiology is altered in humans with major depression. These findings include hypersecretion of cortisol at baseline and on the dexamethasone suppression test. In this review, we present a process-oriented model for HPA axis regulation in major depression.

A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants.

Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression.

Using chronic pain to predict depressive morbidity in the general population.

Background: Pain syndrome is thought to play a role in depression. This study assesses the prevalence of chronic (>or= 6 months' duration) painful physical conditions (CPPCs) (joint/articular, limb, or back pain, headaches, or gastrointestinal diseases) and their relationship with major depressive disorder.

Methods: We conducted a cross-sectional telephone survey of a random sample of 18 980 subjects from 15 to 100 years old representative of the general populations of the United Kingdom, Germany, Italy, Portugal, and Spain.

Depression in the elderly.

Depression is prevalent in the elderly and associated with increased morbidity and mortality. Diagnosis can be complicated by the presence of concomitant medical and/or psychiatric disorders, and it is important to exclude a number of factors, such as neurological disease, hormonal causes, chronic illness, or substance abuse, particularly alcohol. Although comorbid medical illness may contribute to depressive illness, depressive disorders are not a consequence of aging.

Mesotelencephalic dopamine neurochemical responses to glucocorticoid administration and adrenalectomy in Fischer 344 and Lewis rats.

The effects of alterations in peripheral corticosterone levels on multiple dopamine neurochemical estimates were examined in inbred Fischer and Lewis inbred rat strains. 2x2 ANOVA's (treatment x strain) showed a main effect for treatment (1 week CORT versus placebo) on the concentrations of the dopamine metabolites homovanillic acid and dihydroxyphenylacetic acid in the medial prefrontal cortex, with lower levels after treatment, but no significant treatment versus strain interaction. There was no effect of CORT treatment on DA metabolites in the nucleus accumbens shell or dorsal striatum.

Prevalence of depressive episodes with psychotic features in the general population.

Objective: The study evaluated the prevalence of major depressive episodes with psychotic features in the general population and sought to determine which depressive symptoms are most frequently associated with psychotic features.

Method: The sample was composed of 18,980 subjects aged 15-100 years who were representative of the general populations of the United Kingdom, Germany, Italy, Portugal, and Spain. The participants were interviewed by telephone by using the Sleep-EVAL system.

Pharmacological principles of antidepressant efficacy.

Both noradrenaline (NA) and serotonin (5-HT) appear to be involved in depression. Evidence suggests that dual-acting antidepressants, i.e.

Experience-dependent asymmetric variation in primate prefrontal morphology.

Theories of human development suggest that experiences embedded in social relationships alter prefrontal brain systems that mediate emotional self-regulation. This study tests for experience-dependent effects on prefrontal gray and white matter volumes determined in 39 young adult monkeys (Saimiri sciureus) 4 years after conditions that modified early maternal availability. These conditions were previously shown to alter subsequent measures of emotional behavior, social propensities, and hypothalamic-pituitary-adrenal axis stress physiology.

Developing novel treatments for mood disorders: accelerating discovery.

This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics.

An open label trial of C-1073 (mifepristone) for psychotic major depression.

Background: The rationale for treating patients with psychotic major depression (PMD) with glucocorticosteroid receptor (GR) antagonists is explained.

Methods: Thirty patients with PMD, with Hamilton Rating Scale for Depression (HAMD-21) scores of 18 or greater, were assigned in an open label trial to receive 50 mg, 600 mg, or 1200 mg of mifepristone for 7 days.

Results: All the subjects completed the protocol; there were no dropouts.

Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.

Objective: Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase (8 weeks) and an extension phase (16 weeks).

Methods: Patients with major depression and without dementia, at least 65 years old, were eligible; they were randomized to mirtazapine or paroxetine once daily, with doses increasing over 42 days. Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and tolerability was assessed from adverse events.

Slowing the progression of cognitive decline in Alzheimer's disease using mifepristone.

High circulating levels of glucocorticoid hormones adversely affect cognition. Previous studies exploring the hypothalamic-pituitary-adrenal (HPA) axis and basal cortisol levels in the elderly reported that subjects with mid-range cortisol levels outperformed subjects with high cortisol levels on assessments of memory and attention. This study examines the efficacy of mifepristone, a glucocorticoid-antagonist, in decelerating the rate of cortisol-related cognitive decline in subjects with mile-to-moderate Alzheimer's disease (AD).

Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo.

Background: Chronic forms of depression are associated with significant functional and psychosocial impairments. To date, no study has measured psychosocial functioning in this population during long-term maintenance antidepressant treatment or following the double-blind discontinuation of treatment.

Methods: Patients with chronic major or double depression completed 12 weeks of short-term treatment followed by 16 weeks of continuation treatment with sertraline hydrochloride.

Recruiting and retaining future generations of physician scientists in mental health.

The authors discuss 6 challenges facing the recruitment and retention of physician scientists as career mental health researchers. These challenges include (1) early identification and recruitment at the undergraduate and medical student level; (2) recruitment of a more diverse group of trainees; (3) safety nets for reducing attrition; (4) strategies to promote successful competition for K awards; (5) definition of appropriate roles and career development opportunities in multisite clinical trials; and (6) strategies for the mentoring "cost." A coalition of stakeholders--federal, academic, foundational, and in the pharmaceutical industry--is needed to meet these challenges.

Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression.

Background: The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances.

Method: A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.

Relating semantic and episodic memory systems.

Episodic and semantic memory are two forms of declarative memory which appear to function in distinct yet interdependent ways. Here we provide direct evidence for a functional relationship between these two memory systems by showing that left lateral temporal lobe regions involved in semantic memory play an important role in accurate episodic memory retrieval.

Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.

Context: Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated.

Objective: To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors.

Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression.

Background: Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant.

Methods: This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions--Severity and Improvement scales.