Acute Treatment Of Major Depression Research Articles

Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

FDA Approves New Option to Treat Major Depression

FDA Approves New Option to Treat Major Depression

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Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: Clinical Predictors of Outcome in a Multisite, Randomized Controlled Clinical Trial

Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham-controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery-Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial. In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.

Resolution of sexual dysfunction during acute treatment of major depression with milnacipran

The sexual function and enjoyment questionnaire (SFEQ) was developed to assess and detect changes in sexual function in men and women. The aim of the present study was to use the SFEQ to evaluate the effects of the serotonin-noradrenaline reuptake inhibitor, milnacipran, in the treatment of depression in two culturally different populations. The SFEQ was employed in two studies investigating milnacipran in the treatment of major depression: a 12-week open study in Brazil and a 6-week randomised controlled study in Europe. At endpoint, 61.3% (Brazil) and 78.4% (Europe) of patients had >or=50% reduction of baseline Hamilton Depression Rating (HAMD) score. All SFEQ items showed improvements in sexual function in both studies at endpoint, 60% (Brazil) and 56% (Europe) of patients stating that their sexual desire was as great as or greater than it had been before their depressive episode. Milnacipran appears to improve sexual function in parallel with improvement in other symptoms of depression. The SFEQ is a sensitive instrument for measuring changes in sexual function and appears to be unaffected by cultural differences as shown by similar findings in Brazil and Europe.

Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials

Concern has been raised about the efficacy of antidepressant therapy for major depression in adults. We undertook a systematic review of published and unpublished clinical trial data to determine the effectiveness and acceptability of paroxetine. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the GlaxoSmithKline Clinical Trial Register, MEDLINE and EMBASE up to December 2006. Published and unpublished randomized trials comparing paroxetine with placebo in adults with major depression were eligible for inclusion. We selected the proportion of patients who left a study early for any reason as the primary outcome measure because it represents a hard measure of treatment effectiveness and acceptability. We included in our review 29 published and 11 unpublished clinical trials, with a total of 3704 patients who received paroxetine and 2687 who received with placebo. There was no difference between paroxetine and placebo in terms of the proportion of patients who left the study early for any reason (random effect relative risk [RR] 0.99, 99% confidence interval [CI] 0.88-1.11). Paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50% (random effect RR 0.83, 99% CI 0.77-0.90). Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44-2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17-5.54). Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability. These results were not biased by selective inclusion of published studies.

Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

Care Management for Poststroke Depression

See related article, pages 998–1003. Depression is a common consequence of stroke, occurring in one third of people at some point after stroke.1 It is important that depression is viewed as more than an understandable consequence of a sudden-onset major life event, because depression after stroke is associated with poorer rehabilitation outcome,2,3 lower quality of life,4 and suicide.5 Yet few people receive effective management for depression after stroke.1 Cochrane reviews have reported that there is not sufficient evidence for the benefit of pharmacological or psychologic treatments to prevent6 or treat7 depression after stroke. Few adequately powered randomized, controlled trials of interventions for poststroke depression have been conducted. Therefore, the study by Williams et al8 in the current issue of Stroke is a welcome addition to the literature on this important topic. Williams et …

Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse Prevention in Major Depression

Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. Five academic medical centers and their outpatient psychiatry clinics. Two hundred one patients with Structured Clinical Interview for DSM-IV-diagnosed unipolar depression who had remitted with a course of bilateral ECT. Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. Relapse of depression, compared between the C-ECT and C-Pharm groups. In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean +/- SD time to relapse for the C-ECT group was 9.1 +/- 7.0 weeks compared with 6.7 +/- 4.6 weeks for the C-Pharm group (P = .13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed.

Modelling major depression epidemiology and assessing the impact of antidepressants on population health

Randomized controlled trials indicate that antidepressant treatment increases the probability of remission in acute treatment of major depression, diminishes the frequency of relapse during continuation phase treatment and diminishes the risk of recurrence during maintenance treatment. As antidepressant coverage increases in the population, the benefits of antidepressant treatment should begin to translate into improved population health. However, adverse effects can also occur, as can unnecessary treatment. Monitoring the impact of antidepressant treatment on population health should be a priority for health surveillance. Quantitative description of the relationship between treatment provision and population health status will require the use of epidemiological models. A variety of such models have been reported in the literature. None of the existing models, however, are fully satisfactory.

Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition

Since the publication in 2000 of APA’s Practice Guideline for the Treatment of Patients With Major Depressive Disorder (2nd Edition) (1), two important safety concerns have emerged (hepatotoxicity with nefazodone, and suicide risk and antidepressants), and two new antidepressants have been approved for use (escitalopram and duloxetine). This watch describes these developments as well as evidence that has accrued since 2000 in other areas related to the treatment of major depressive disorder.

Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression

Existing therapies for major depressive disorder (MDD) have either limited efficacy and/or poor tolerability. The present study examined the effects of duloxetine, a potent and balanced dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE), in patients with MDD. Adult patients ( N=267) with MDD were randomly assigned to receive duloxetine (60 mg/day) or placebo in this 9-week, multi-center, double-blind, parallel-group clinical trial. Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD 17), Visual Analog Scales (VAS) for pain, Clinical Global Impression of Severity (CGI-S), Patient's Global Impression of Improvement (PGI-I), and Quality of Life in Depression Scale (QLDS). Safety was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. Duloxetine (60 mg QD) significantly reduced the HAMD 17 total score compared with placebo at the end of 9-week therapy. Estimated probabilities of response and remission were 65 and 43%, respectively, for duloxetine compared with 42 and 28% for placebo. Duloxetine also reduced overall pain, back pain, shoulder pain and time in pain while awake significantly more than placebo. Global measures of improvement, including PGI-I and QLDS, were significantly improved by duloxetine compared with placebo. Discontinuations due to adverse events were more frequent for duloxetine-treated patients (12.5%) than for placebo-treated patients (4.3%). Nausea, dry mouth, dizziness, and constipation were more frequent for duloxetine than placebo. There was no significant incidence of hypertension, nor any other safety issues. Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD.

Treating children and adolescents with selective serotonin reuptake inhibitors: how long is appropriate?

This article addresses a key question on the use of selective serotonin reuptake inhibitors (SSRIs) among children and adolescents. As briefly reviewed, recent randomized controlled trials have established the safety and efficacy of SSRIs in the acute treatment of major depression and anxiety disorders among children and adolescents. Major questions emerge in light of these data concerning the potential risks and benefits of long-term SSRI use among children and adolescents who receive significant short-term benefits from SSRI treatment. The current review summarizes research on longitudinal outcomes, neuroscience, and psychopharmacology to formulate a set of preliminary recommendations on long-term SSRI use. A review of data in these areas supports three conclusions. First, for children who achieve marked reduction in anxiety or depressive symptoms on an SSRI, clinicians should consider recommending a medication-free trial. Second, when indicated, this medication-free trial should coincide with the first low-stress period occurring after 1 year of continual SSRI treatment. Third, SSRI treatment should be reinitiated in children who exhibit signs of relapse during this medication-free trial.

Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression

Background: Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety. Methods: Patients ( N=108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score ≥7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed. Results: Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated. Conclusion: These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression.

Current Perspectives on the Diagnosis and Treatment of Double Depression.

In recent years, the frequency with which patients present with 'double depression', i.e. coexisting chronic depression (dysthymia) and acute major depression, has become increasingly evident. A growing research literature demonstrates that patients with double depression are at increased risk for poor outcome, including poor psychosocial functioning, high usage of medical services, high rates of suicide attempts, and increased recurrence of major depression. Furthermore, naturalistic studies have shown that when these patients are treated in the community, they often do not receive adequate antidepressant medication to treat their acute or chronic depressive disorders.In this article, we introduce a typology that is designed to assist clinicians in determining useful strategies in the short and long term treatment of double depression. This differentiates between those patients with double depression who present primarily with acute depression; those presenting primarily with chronic depression (where treatment can focus on the single, more severe disorder, and may be time-limited or episodic); and those presenting with severe acute depression and severe chronic depression, in whom lifelong medication is often required. Aggressive treatment is recommended for all patients with double depression, but refined treatment strategies based on depressive typology may help to increase compliance, consolidate therapeutic gains and forestall relapse.A growing psychopharmacology literature shows that several different classes of medication [tricyclic antidepressants, monamine oxidase inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and others] are effective in the treatment of double depression, although perhaps somewhat less effective than in the treatment of acute major depression.

Hopelessness in suicide attempters after acute treatment of major depression in late life

The relation between hopelessness and suicide attempts in the elderly was examined by studying the course of hopelessness in depressed patients. Sixty-three elderly patients with recurrent major depression were treated with nortriptyline and interpersonal psychotherapy and underwent serial ratings of hopelessness and depression during the acute and continuation phases of treatment. Patients who had made a suicide attempt in the past had significantly higher hopelessness scores than nonattempters during both phases of treatment. They were also more likely to drop out of treatment. A high degree of hopelessness persisting after remission of depression in elderly patients appears to be associated with a history of suicidal behavior. It may also increase the likelihood of premature discontinuation of treatment and lead to future suicide attempts or suicide.

Comparison of mania and depression after brain injury: causal factors.

Patients who developed secondary mania after brain injury (N = 17) had a significantly greater frequency of injury to right hemisphere areas connected with the limbic system than poststroke patients with major depression (N = 31), who had injury primarily in the left frontal cortex and basal ganglia. For patients without mood disturbance after brain injury (N = 28), the location of the lesion was not significant. Secondary mania patients also had a significantly greater frequency of family history of affective disorder than did the other two groups. These results suggest that an interaction between injury to certain areas of the right hemisphere and genetic factors or other neuropathological conditions produces secondary mania.