Showing papers on "Treatment-resistant depression published in 2011"
TL;DR: Deep brain stimulation remains a safe and effective treatment for treatment-resistant depression and functional impairment in the areas of physical health and social functioning progressively improved up to the last follow-up visit.
Abstract: Objective:A prevalence of at least 30% for treatment-resistant depression has prompted the investigation of alternative treatment strategies. Deep brain stimulation (DBS) is a promising targeted approach involving the bilateral placement of electrodes at specific neuroanatomical sites. Given the invasive and experimental nature of DBS for treatment-resistant depression, it is important to obtain both short-term and long-term effectiveness and safety data. This report represents an extended follow-up of 20 patients with treatment-resistant depression who received DBS to the subcallosal cingulate gyrus (Brodmann's area 25). Method:After an initial 12-month study of DBS, patients were seen annually and at a last follow-up visit to assess depression severity, functional outcomes, and adverse events. Results:The average response rates 1, 2, and 3 years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. At the last follow-up visit (range=3–6 years), the average response rate was 64.3%. Functional ...
433 citations
TL;DR: Deep brain stimulation (DBS) is one of the most invasive focal neuromodulation techniques available; data have supported its safety and efficacy in a number of movement disorders.
Abstract: Medications, psychotherapy, and other treatments are effective for many patients with psychiatric disorders. However, with currently available interventions, a substantial number of patients experience incomplete resolution of symptoms, and relapse rates are high. In the search for better treatments, increasing interest has focused on focal neuromodulation. This focus has been driven by improved neuroanatomical models of mood, thought, and behavior regulation, as well as by more advanced strategies for directly and focally altering neural activity. Deep brain stimulation (DBS) is one of the most invasive focal neuromodulation techniques available; data have supported its safety and efficacy in a number of movement disorders. Investigators have produced preliminary data on the safety and efficacy of DBS for several psychiatric disorders, as well. In this review, we describe the development and justification for testing DBS for various psychiatric disorders, carefully consider the available clinical data, a...
297 citations
TL;DR: The results suggest that nonrefractory and refractory depression are characterized by distinct functional deficits in distributed brain networks.
Abstract: Objective: The authors used resting-state functional connectivity MRI to evaluate brain networks in patients with refractory and nonrefractory major depressive disorder
291 citations
TL;DR: Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression, and MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials.
137 citations
TL;DR: The use of cognitive behaviour therapy is recommended for unipolar TRD, but there is no evidence supporting its use in bipolar TRD; other non-pharmacological strategies such as deep brain stimulation may be promising alternatives for the future.
Abstract: The phenomenon of treatment-resistant depression (TRD), described as the occurrence of an inadequate response after an adequate treatment with antidepressant agents (in terms of dose, duration, and adherence), is very common in clinical practice. It has been broadly defined in the context of unipolar major depression, but alternative definitions for bipolar depression have also been suggested. In both cases, there is a remarkable lack of consensus amongst professionals concerning its operative definition. A relatively wide variety of treatment options for unipolar TRD are available, whilst the evidence is very scanty for bipolar TRD. TRD is associated to poor clinical, functional, and social outcomes. Several novel therapeutic options are currently being investigated as promising alternatives, targeting the neurotransmitter system outside of the standard monoamine hypothesis. Augmentation or combination with lithium or atypical antipsychotics appears as a valid option for both conditions, and the ...
135 citations
TL;DR: Stereotactic pharmacological inhibition of the LHb exerted antidepressive effects in treatment resistant cLH rats and used the gamma-aminobutyric acid agonist muscimol to inhibit the LHB in Sprague-Dawley rats with congenital learned helplessness.
134 citations
TL;DR: High doses of daily left prefrontal repetitive transcranial magnetic stimulation may safely be used in outpatients with major depressive episode even as an adjunctive treatment, and suicidal ideation diminished in 67% of the patients after just 1 week.
Abstract: Objective:Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) recently received Food and Drug Administration (FDA) approval for the treatment of depression and offers an alternative to traditional approaches. This approval was based on a study using 3000 stimuli per day (15,000
132 citations
TL;DR: Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people.
Abstract: Objective:The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older). Method:The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies. Results:All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI=42–62; N=381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI=21–65; N=57). Only two studies included compari...
118 citations
TL;DR: Using Momentary assessment technology as a tool to help patients with depression help themselves to help themselves in the treatment of depression.
Abstract: Objective: Given high relapse rates and residual symptoms in depression, new strategies to increase treatment effectiveness are required. A promising avenue is to investigate how electronic momentary assessment technology may contribute to clinical assessment and interventions in depression. Method: A literature search was conducted focusing on the potential contribution of momentary assessments to clinical applications in depression. Results: Momentary assessments are able to reveal subtle, small but repetitive and relevant patterns of emotional expression that predict future course of depression. A momentary assessment tool may expose manageable pieces of daily life behaviour contributing to the depressive experience that patients can influence. The use of this explicit knowledge of daily life experience is understudied with regard to its contribution to diagnostic assessment, monitoring of treatment effects and feedback interventions in depressed patients. The clinical application of momentary assessments may stimulate a shift from passive consumption of treatment to an active role for patients in their recovery and increased patient ownership. Conclusion: The precise, prospective and fine‐grained information that momentary assessment technology provides may contribute to clinical practice in various ways. Future studies should examine the clinical impact of its use and the feasibility of its implementation in mental health care.
118 citations
TL;DR: It is found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice, with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile.
Abstract: OBJECTIVE To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation (VNS) following US Food and Drug Administration (FDA) approval of this intervention. METHOD We implanted a VNS device in 15 consecutive outpatients with treatment-resistant major depressive episodes, including 10 with major depressive disorder and 5 with bipolar disorder (DSM-IV criteria), between November 2005 and August 2006. Existing antidepressant treatment remained fixed as far as clinically possible. The primary outcome was change from baseline in the Beck Depression Inventory (BDI) score. Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS. RESULTS The BDI score decreased significantly compared to baseline at 6 months (P < .05) and 12 months (P < .01), from a mean of 37.8 (SD = 7.8) before VNS activation to a mean of 24.6 (SD = 11.4) at 12 months. By 1 year, 28.6% (n = 4) of the sample responded to VNS and 7.1% (n = 1) remitted according to the BDI. Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year, with a 43% response rate (n = 6) and 14.3% remission rate (n = 2). No obvious predictors of response were detected. Side effects of VNS included hoarseness (73%), dyspnea (47%), nausea (40%), pain (33%), and anxiety (20%); no patient terminated treatment due to intolerable side effects. CONCLUSIONS We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice, with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile.
114 citations
TL;DR: In depressed nonresponders to a previous antidepressant treatment, switching to a different class of antidepressants was not associated with a better response or remission rate and the evidence supporting the commonly suggested sequential use of antidepressants from 2 different pharmacological classes is weak.
Abstract: Objective:The management of treatment-resistant depression is a much debated issue. In particular, the evidence supporting the commonly suggested sequential use of antidepressants from 2 different pharmacological classes is weak.This retrospective study was undertaken to investigate whether there is
TL;DR: The nature and correlates of abuse that might explain a history of abuse being associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study are reported on.
Abstract: Objective We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N = 334) were randomized to one of the following: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12-week response rate to combination therapy compared with medication mono-therapy (62.8% versus 37.6%; odds ratio [OR] = 2.8, 95% confidence interval [CI] = 1.6-4.7, p p = .66), whereas those with history of PA had a much lower rate of response to combination therapy (18.4% versus 52.4%, OR=0.1; 95% CI=0.02–0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion These results should be considered within the limitations of a post hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response. Clinical Trial Registry Information: Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); NCT00018902; http://www.clinicaltrials.gov.
TL;DR: Both SGA monotherapy and adjunctive therapy showed greater efficacy in the treatment of MDD than placebo, but augmentation is more widely utilized in treatment-resistant depression.
Abstract: Purpose of reviewThe aim of this systematic review was to examine the efficacy and safety of second-generation antipsychotics (SGAs) in nonpsychotic major depressive disorder (MDD).Recent findingsIn MDD, SGA monotherapy or adjunctive therapy to conventional antidepressants showed rapid onset of anti
TL;DR: This work begins to ask what the basis of treatment resistance is, and proposes new strategies to model this phenomenon in animals, focusing specifically on animal models that offer the appropriate framework to study treatment resistance with face, construct and predictive validity.
TL;DR: Research into deep brain stimulation in the treatment of depression has shown promising results in animals and in patients with a history of depression.
Abstract: Objective: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD). Method: A re ...
TL;DR: The definition, prevalence, clinical significance, risk factors, and management of treatment‐resistant depression in adolescents in adolescents are reviewed.
Abstract: Treatment-resistant depression (TRD) in adolescents is prevalent and impairing. We here review the definition, prevalence, clinical significance, risk factors, and management of TRD in adolescents. Risk factors associated with TRD include characteristics of depression (severity, level of hopelessness, and suicidal ideation), psychiatric and medical comorbidities, environmental factors (family conflict, maternal depression, and history of abuse), and pharmacokinetics and other biomarkers. Management options include review of the adequacy of the initial treatment, re-assessment for the above-noted factors that might predispose to treatment resistance, switching antidepressants, and augmentation with medication or psychotherapy. Other modalities, such as electroconvulsive therapy, vagal nerve stimulation, and repetitive transcranial magnetic stimulation, are also reviewed.
TL;DR: It is proposed that neuroplastic processes related to dendritic arborization may underlie the treatment resistant depression that occurs in the setting of chronic antidepressant use, and the term tardive dysphoria is proposed.
TL;DR: ACAPS may represent an effective intervention for some patients with chronic, disabling, treatment refractory major depression that has failed to respond to other therapeutic approaches, and the adverse effect burden within this population was modest.
Abstract: Background There is very limited evidence for the efficacy of any specific therapeutic intervention in chronic, treatment refractory major depression. Thermal anterior capsulotomy (ACAPS) is a rarely performed but established therapeutic procedure for this patient group. While benefit has been claimed, previous ACAPS reports have provided limited information. Detailed prospective reporting of therapeutic effects and side effects is required. Objective To report a prospective study of therapeutic effect, mental status, quality of life, social functioning and neurocognitive functioning in individuals with chronic treatment refractory major depression, treated with ACAPS. Method A prospective case series of 20 patients treated with ACAPS between 1992 and 1999 were reassessed at a mean follow-up of 7.0±3.4 years. Data were collected preoperatively and at long term follow-up. Structural MRI was performed in 14 participants. Results According to a priori criteria, at long term follow-up, 50% were classified as ‘responders’ and 40% as ‘remitters’. Fifty-five per cent were classified as ‘improved’; 35% were ‘unchanged’; and 10% had ‘deteriorated’. Neurocognitive and personality testing were not significantly different at follow-up. A trend towards improvement in some aspects of executive neuropsychological functioning was observed. Significant adverse effects were infrequent and there were no deaths. Conclusions ACAPS may represent an effective intervention for some patients with chronic, disabling, treatment refractory major depression that has failed to respond to other therapeutic approaches. The adverse effect burden within this population was modest, with no evidence of generalised impairment of neurocognitive functioning.
TL;DR: The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions.
31 Aug 2011
TL;DR: Patients with two or more prior treatment failures are considered to have treatment-resistant depression (TRD); these TRD patients represent a complex population with a disease that is difficult to manage.
Abstract: Major depressive disorder (MDD) is common and costly. Over the course of a year, between 13.1 million and 14.2 million people will experience MDD. Approximately half of these people seek help for this condition, and only 20 percent of those receive adequate treatment. For those who do initiate treatment for their depression, approximately 50 percent will not adequately respond following acutephase treatment; this refractory group has considerable clinical and research interest. Patients with only one prior treatment failure are sometimes included in this group, but patients with two or more prior treatment failures are a particularly important and poorly understood group and are considered to have treatment-resistant depression (TRD). These TRD patients represent a complex population with a disease that is difficult to manage.
TL;DR: This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and depression and the role of early life stress as an important risk factor for HPA axis dysregulation and suggests this dysregulation is partially attributable to an imbalance between glucocorticoid and mineralocortioid receptors.
Abstract: evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology, especially depression. The most recent studies reviewed herein suggest that early life stressors are associated with an increased risk for mood disorders in adulthood. This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and depression and the role of early life stress as an important risk factor for HPA axis dysregulation. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. Moreover, HPA axis changes appear to be state- dependent, tending to improve upon resolution of the depressive syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during antidepressant treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in major depression, but few studies have assessed the activity of mineralocorticoid receptors in depression. Thus, more studies are needed to elucidate this issue. Keywords: early life stress, childhood trauma, depression, treatment-resistant depression, hypothalamic-pituitary-adrenal axis.
TL;DR: Review demonstrates the utility of psychotherapy in managing treatment resistant depression, however, evidence is sparse and results are mixed, given that quality trials are lacking.
Abstract: OBJECTIVE
To examine the utility of psychotherapy in managing treatment resistant depression.
TL;DR: A modified version of MCBT, which includes the use of metaphor and adaptations of the original intervention will be discussed through the clinical case of a woman with long-standing TRD.
TL;DR: Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD.
Abstract: To compare the efficacy and safety of augmenting paroxetine with risperidone, buspirone, valproate, trazodone, or thyroid hormone in patients with treatment-resistant depression (TRD), 225 patients with retrospectively and/or prospectively identified stage II TRD were randomly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45), sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100 mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study. Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study, response rate based on 17-item Hamilton Rating Scale for Depression total score of 50% improvement or greater from baseline, and the change in scores of Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey, and the Life Satisfaction Rating Scale. The remission rates were 26.7% for risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and 37.5% for thyroid hormone. There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events. Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD. Large-sample studies are warranted to support or refute these findings.
TL;DR: Although it is still suggested that ACS patients with first and new-onset depression are at particularly increased risk of worse prognosis, the inconsistent results from the studies included in this systematic review show that there is no consistent evidence to support such statements.
Abstract: Background: Depression after acute coronary syndrome (ACS) is associated with worse cardiac outcomes. This systematic review evaluated whether depressed ACS patients are at differential risk depending on the recurrence and timing of onset of depressive episodes. Methods: MEDLINE, EMBASE and PsycINFO were searched from inception to 11 April 2009. Additionally, reference lists and recent tables of contents of 34 selected journals were manually searched. Eligible studies evaluated cardiovascular outcomes for subgroups of ACS patients with depression or depressive symptoms according to recurrence or onset. Results: Six studies were included that reported outcomes for subgroups of ACS patients with first-ever versus recurrent depression. Four of these reported also outcomes for post-ACS onset versus pre-ACS onset depression, and incident versus nonincident depression. Worse outcomes (odds ratio >1.4) were reported for ACS patients with first-ever depression in 3 of 6 studies (1 study p < 0.05), for patients with post-ACS onset depression in 3 of 4 studies (1 study p < 0.05, but better outcomes in one study) and for patients with incident depression in 2 of 4 studies (no studies p < 0.05). Conclusions: Although it is still suggested that ACS patients with first and new-onset depression are at particularly increased risk of worse prognosis, the inconsistent results from the studies included in this systematic review show that there is no consistent evidence to support such statements.
TL;DR: The results suggest that aspirin can be served as an effective adjunctive agent in the treatment resistant depression mediated by inhibition of the COX-2 level and PGE(2) concentration.
TL;DR: Track patients' depressive symptoms with standardized measurement tools during the course of treatment is necessary for identifying incomplete remission and providing appropriate treatment modification.
Abstract: Full symptomatic remission is the optimal outcome for patients with major depression. Unfortunately, initial antidepressant efficacy is limited to partial response for many patients. Incomplete remission of depressive symptoms is associated with increased risk of relapse, decreased functioning in work and social settings, and increased risk of suicide. Factors that increase the likelihood of treatment resistance include chronicity, severe symptomatology, and comorbid illnesses. Strategies to manage patients who do not respond to an initial course of antidepressant medication include optimizing the dose, switching antidepressants, or adding adjunctive treatment (ie, psychotherapy or a second medication). Augmentation may be the preferred strategy for improving response if tolerability to the original agent is acceptable and the initial medication has had some beneficial effects. Tracking patients' depressive symptoms with standardized measurement tools during the course of treatment is necessary for identifying incomplete remission and providing appropriate treatment modification.
TL;DR: This study supports the thesis that switching from an SSRI to a TCA (and vice versa) in non-responders to a 4-week trial of an SSri/TCA is not associated with improved response, and the result goes in the opposite direction to that predicted by current guidelines.
Abstract: OBJECTIVES. Evidence in favour of switching between selective serotonin reuptake inhibitor (SSRI) and tricyclic (TCA) antidepressants in treatment resistant depression has been tested in a few studies only, consequently a prospective study was undertaken to evaluate the impact of switching strategies. METHODS. One hundred eighty-nine patients who failed to respond to a previous antidepressant were randomised to four arms: firstly they received citalopram or desipramine for a 4-week period; secondly, those who failed to respond were treated for a further 4-week period with the same antidepressant (citalopram-citalopram and desipramine-desipramine arms) or switched to the alternate one (citalopram-desipramine and desipramine-citalopram arms). RESULTS. There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression (HRSD), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression (CGI) scores. In the second 4-week phase remitter rates were higher among non-switched patients (P = 0.04). Moreover, considering HRSD and MADRS, switched patients reported significantly higher scores (P ≤ 0.02 for both scales at each time-point). CONCLUSIONS. This study supports the thesis that switching from an SSRI to a TCA (and vice versa) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response. The result goes in the opposite direction to that predicted by current guidelines.
TL;DR: This interesting letter by Murrough et al presented us with a dilemma: on the one hand it’s an interesting case, with a good outcome, but this is only a single case, which means the authors can draw no conclusions, and some of the authors hold a use patent on ketamine (appropriately disclosed) and could profit from the agent if it is approved for marketing.
Abstract: This interesting letter by Murrough et al presented us with a dilemma. On the one hand it’s an interesting case, with a good outcome. Treatment-resistant depression is a huge public health burden, and options are many but confusing. Add to the positives that intravenous ketamine is intriguing, with encouraging results and a mechanism that differs from traditional antidepressants. But this is only a single case, which means we can draw no conclusions. And some of the authors hold a use patent on ketamine (appropriately disclosed) and could profit from the agent if it is approved for marketing. On balance, we chose to share it with our clinical readership—with the duly noted caveats.
TL;DR: The results suggest that HF rTMS, when used as an augmenting strategy, positively affects depressive and anxious symptoms as well as QOL in patients with severe TRD, but further studies are needed to better clarify the preliminary findings.