Showing papers on "Treatment-resistant depression published in 2006"

Acute and Longer- Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

Abstract: Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of ≤5 on the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR 16 ) (equivalent to ≤7 on the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) defined remission; a QIDS-SR 16 total score of ≥11 (HRSD 17 ≥14) defined relapse. Results: The QIDS-SR 16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, t...

Treatment-resistant depression

Abstract: Treatment-resistant depression (TRD) is a common clinical occurrence among patients treated for major depressive disorder. However, a clear consensus regarding the criteria defining TRD is lacking in the psychiatric community. Many patients who are considered treatment resistant are actually mis-diagnosed or inadequately treated. Clinicians need to accurately diagnose TRD by examining primary and secondary (organic) causes of depression and acknowledging paradigm failures that contribute to a misdiagnosis of TRD. A correct determination of what constitutes TRD requires consensus on criteria of treatment response (i.e., dose, duration, and compliance) and on the number of adequate trials required before a patient is determined to be nonresponsive. Additionally, clinical validation of available staging models needs to be completed. While several studies have identified predictors of non-response, clinical studies investigating the predictors of resistance following the failure of 2 or more antidepressant trials should be pursued. In managing TRD, 3 pharmacotherapy strategies are in clinical use: optimization of antidepressant dose, augmentation/combination therapies, and switching therapies. However, the optimal strategy for treating TRD has yet to be identified. Therefore, further controlled clinical trials are essential to identify the most effective treatment strategies.

An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression.

Abstract: Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing active investigation for use in the treatment of major depression. Recent research has indicated that current methods used to localize the site of stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly inaccurate. However, little information is available on which to base a choice of stimulation site. The aim of the current study was to systematically examine imaging studies in depression to attempt to identify whether there is a pattern of imaging results that suggests an optimal site of stimulation localization. We analysed all imaging studies published prior to 2005 that examined patients with major depression. Studies reporting activation in DLPFC were identified. The DLPFC regions identified in these studies were analysed using the Talairach and Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a quantitative meta-analysis of resting studies and studies of serotonin reuptake inhibitor antidepressant treatment. There was considerable heterogeneity in the results between studies. Changes in Brodmann area 9 were relatively consistently identified in resting, cognitive activation and treatment studies included in the meta-analysis. However, there was little consistency in the direction of these changes or the hemisphere in which they were identified. At this stage, the results of imaging studies published to date have limited capacity to inform the choice of optimal prefrontal cortical region for the use in rTMS treatment studies.

Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression.

Abstract: BACKGROUND Treatment-resistant depression (TRD) is a long-term, disabling illness. We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with standard care. METHOD This 2-year prospective, multicenter, observational study (patients enrolled from January 2001 through July 2004) tracked the outcomes of 124 patients with treatment-resistant, nonpsychotic major depressive disorder (N = 109) or bipolar depressed phase disorder (N = 15) who received treatment as usual (TAU) (i.e., any therapeutic regimen agreed to by patients and psychiatrists, including medications, electroconvulsive therapy [ECT], and psychotherapy). Treatments could be adjusted, started, and stopped as necessary. The primary outcome, treatment response, was defined a priori as > or = 50% improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR-30). Remission was defined as an IDS-SR-30 score of < or = 14. The Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) was used to monitor quality-of-life changes. RESULTS The 12- and 24-month IDS-SR-30 response rates were 11.6% (13/112) and 18.4% (19/103), respectively. Of the 13 responders at 12 months, only 5 were responders at 24 months. The 12- and 24-month IDS-SR-30 remission rates were 3.6% (4/112) and 7.8% (8/103), respectively. Only 1 of the 4 12-month remitters was also a remitter at 24 months. The SF-36 indicated globally poor quality of life in this sample. CONCLUSIONS Despite the wide range of treatment options available for depression, the response rates, remission rates, and quality-of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU.

A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.

Abstract: We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.

Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study.

Abstract: This pilot study examined the effectiveness of Intensive Short-term Dynamic Psychotherapy (ISTDP) in treatment-resistant depression (TRD). Ten patients with TRD were provided a course of ISTDP. Clinician and patient symptom and interpersonal measures were completed every 4 weeks, at termination, and in follow-up. Medication, disability, and hospital costs were compared before and after treatment. After an average of 13.6 sessions of therapy, all mean measures reached the normal range, with effect sizes ranging from 0.87 to 3.3. Gains were maintained in follow-up assessments. Treatment costs were offset by cost reductions elsewhere in the system. This open study suggests that ISTDP may be effective with this challenging patient group. A randomized, controlled trial and qualitative research are warranted to evaluate this treatment further and to examine its possible therapeutic elements.

Efficacy and Mechanisms of Action of Lithium Augmentation in Refractory Major Depression

Abstract: Lithium augmentation refers to the addition of lithium to an antidepressant in the acute treatment phase of patients with depressive episodes who have failed to respond satisfactorily to treatment with antidepressant monotherapy. This article reviews the clinical evidence and hypotheses on the mode of action of lithium augmentation. For this purpose, studies were identified by searching Medline and by scanning the references of published reviews and standard textbooks. With regard to efficacy, 28 prospective studies (with a total of 838 depressed patients) were identified. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation. A recent meta-analysis including only double-blind, placebo-controlled trials (N = 9) provided firm evidence that lithium augmentation has a statistically significant effect on response rate compared to placebo, and showed that lithium augmentation should be administered for at least 2 weeks to allow assessment of the patient's response. A recent double-blind, placebo-controlled trial revealed that responders to lithium augmentation should be maintained on the lithium-antidepressant combination for a minimum of 12 months. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly through a synergistic action of lithium and the antidepressant on brain 5-HT pathways. Neuroendocrine studies in humans on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined dexamethasone/CRH test. These results are in contrast to the established decline of HPA system activity during treatment with antidepressants. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment.

An open-label, rater-blinded, augmentation study of aripiprazole in treatment-resistant depression.

Abstract: Background: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D2 and serotonin 5-HT1A receptors and antagonism at the 5-HT2 receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. Method: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10–30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. Results: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). Conclusions: The study indicates the potential utility of aripiprazole as an augmenting agent in treatment-resistant depression, particularly in those who had failed 2 or more antidepressant trials. Adequately powered, randomized controlled trials are necessary to evaluate the role of aripiprazole in treatment-resistant depression.

Realistic expectations and a disease management model for depressed patients with persistent symptoms.

Abstract: Objective: To describe the efficacy of currently available treatments for depression in achieving remission and to highlight additional strategies for those patients who continue to experience persistent depressive symptoms in spite of optimal treatment. Data Sources: The authors reviewed the literature (electronic and hand searches) on the efficacy of current pharmacologic and psychotherapeutic antidepressant treatments and the utility of a chronic disease management model. A search of PubMed was conducted for English-language articles published from 1980 to 2005 using the keywords depression treatments, outcome, course of illness, and treatment resistant depression. Data Synthesis: Current treatments for depression leave a significant minority (20%-40%) of patients with persistent depressive symptoms. A disease management model that may be useful for major depressive disorder is described. Conclusions: The goal of treating depression to achieve remission, although ideal, is currently unattainable for many patients. The long-term care of patients with persisting depressive symptoms may be well served by adding a disease management component to the overall treatment strategy. Doing so may help to improve coping, interpersonal functioning, and quality of life.

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study.

Abstract: We evaluated the efficacy and safety of vagus nerve stimulation therapy in the treatment of 11 patients with chronic treatment-resistant depression. Mood was evaluated at frequent intervals over the year following implantation. All measures of depression, including the Hamilton Rating Scale for Depression reduced significantly. The response and remission rates were 55% and 27% respectively at 1 year. Side-effects were common, and some were severe.

Quetiapine augmentation in treatment-resistant depression: a naturalistic study

Abstract: Treatment-resistant depression (TRD) is a common clinical problem, often complicated with suicidal ideations and greater lifetime functional impairment, and represents a considerable challenge to management and treatment. The aim of a prospective, open-label, noncomparative, flexible-dosed 20-week study was to evaluate the effects of quetiapine, as an add-on therapy, in patients with TRD who were refractory to previous treatments. Eighteen patients with major depressive disorder (DSM-IV criteria) were treated for 20 weeks with quetiapine (mean dose 315±109 mg/day). Patients were evaluated at baseline, weekly from 1 to 9 weeks, and then after 12, 16, and 20 weeks of treatment, using Hamilton rating scale for depression–17 items (HAMD) scale. Fourteen patients with TRD completed the 20-week open trial with quetiapine. The augmentation with quetiapine significantly reduced total scores and scores listed in the anxiety subscale on the HAMD, and these effects were observed after the fourth week of treatment, while the depressed mood scores were significantly reduced after the fifth week of treatment. Quetiapine add-on treatment significantly decreased the scores listed in the insomnia subscale on the HAMD subscale after the second week of treatment. Our preliminary data indicate that quetiapine add-on therapy appears to have beneficial effects in the treatment of patients with TRD.

Deep brain stimulation for treatment-resistant depression: a psychiatric perspective.

Abstract: Traditionally, the therapeutic approach to treatment-resistant depression (TRD) has relied on pharmacotherapy in various sequences and combinations, in addition to evidence-based psychotherapy or electroconvulsive therapy. Despite refinements to the existing therapeutic modalities, there remains a significant subpopulation of severely ill patients with refractory mood disorders who fail to achieve a clinical response despite aggressive psychosocial and biological treatments. Interest in the use of deep brain stimulation (DBS) for treatment-resistant psychiatric illness has emerged in recent years for a number of reasons: 1) as part of a general re-evaluation of both noninvasive and invasive brain stimulation techniques, 2) because of the demonstrated clinical efficacy of DBS for movement disorders, and 3) as a logical consequence of studies defining the functional neurocircuitry of several psychiatric disorders. This review will examine the progress of DBS in the treatment of Parkinson's disease and the potential implications for its use in TRD, as well as the role of the psychiatrist in selection and ongoing management of patients who receive this procedure.

Acute and long-term VNS effects on pain perception in a case of treatment-resistant depression.

Abstract: Vagus Nerve Stimulation (VNS) is approved by the FDA for treatment of both epilepsy and depression. Recent work has shown that VNS acutely affects pain perception in humans, actually increasing pain sensitivity momentarily while the device is firing. It is unclear how this acutely increased sensitivity might change over time with treatment and how it might relate to longer-term therapeutic effects of VNS on pain. We describe a patient with treatment-resistant depression and a history of severe lumbar degenerative disease with resultant chronic low back pain. His depression and pain symptoms both seemed to respond to VNS. He eventually stopped all medications and remained depression and pain free for 35 months with no change in his device settings. Sixty-six months after VNS implantation and 64 months after his initial clinical antidepressant response, under single-blind conditions, we performed quantitative sensory testing with laboratory thermal pain procedures during acute VNS-on and -off conditions. Interestingly, despite a significant and profound anti-nociceptive clinical response for the previous 35 months, he had significant increases in painfulness ratings while the VNS device was actively firing compared with device-off conditions. This case suggests that VNS-induced acute increases in pain sensitivity can coexist with a clinical anti-nociceptive response. If the acutely increased sensitivity sets the stage for the slower chronic anti-pain effects, the increased acute sensitivity does not disappear. Acute and chronic effects of VNS on pain perception merit further research.

Concomitant use of vagus nerve stimulation and electroconvulsive therapy for treatment-resistant depression.

Abstract: Objective: This study explored the use of electroconvulsive therapy (ECT) in the pivotal study of vagus nerve stimulation (VNS) for treatment-resistant depression. Methods: The clinical characteristics and outcomes of study participants who received ECT during the first 12 months of VNS were compared with those who did not receive ECT. Physicians were instructed to turn off VNS during administration of ECT. Results: Of 205 (evaluable sample) patients who received VNS, 14 also received ECT. Participants who received ECT had a statistically significant greater number of hospital admissions (P = 0.037, Wilcoxon) and number of suicide attempts during their lifetimes (P= 0.022, Fisher exact test). Of 55 responders (≥50% reduction in Hamilton Rating Scale for Depression-24 questions [HRSD-24] scores) after 12 months of VNS, 3 had received ECT. Of 32 remitters (HRSD-24 score, ≤9), 2 had received ECT. Administration of ECT did not affect the implanted VNS device, and the presence of the implanted VNS device did not affect the administration of ECT. Conclusions: Electroconvulsive therapy and VNS are not mutually exclusive. They can be used safely and effectively either sequentially or concurrently. Each can be prescribed as the depressive condition warrants-ECT for emergently worsening depressive symptoms and maintenance therapy and VNS for chronic, long-term therapy.

Vagus nerve stimulation therapy for treatment of drug-resistant epilepsy and depression.

Abstract: Vagal nerve stimulation therapy is a new adjunctive treatment for drug-resistant epilepsy and depression. It consists of a pulse generator that transmits impulses to the left vagus nerve via an implantable electrode and can be performed by surgeons familiar with the anatomy of the cervical vagus nerve. The minimum age for vagal nerve stimulation therapy for epilepsy is 12 years, and for depression, 18 years. Hoarseness and cough are the most common side effects. Response rates to vagal nerve stimulation therapy vary and depend on several other factors. If used as adjunctive therapy, vagal nerve stimulation has shown better control of seizures or depression at smaller doses of antiepileptic or antidepressive medications and also results in decreased dose-dependent side effects. Vagal nerve stimulation therapy appears safe as an adjunctive treatment for drug-resistant epilepsy and depression. Long-term data are needed to better define its ultimate role in various subsets of patients.

Which factors are important predictors of non-recovery from major depression? A 2-year prospective observational study.

Abstract: Our aim was to study factors associated with long-term non-recovery from major depression. A total of 109 patients with major depression were followed prospectively for 2 years. A diagnosis of major depression based on SCID interviews at follow-up indicated non-recovery. The effect of several established risk factors was assessed. A third (30%) of the patients did not recover. Severity of initial depression were associated with poor outcome according to univariate analysis. Nevertheless, personality disorder and rural area of residence were associated with non-recovery in final multivariate analysis. Major depression in patients with personality disorder should be treated as effectively as possible. Moreover, service planning in rural areas needs attention.

Daily and spaced treatment with transcranial magnetic stimulation in major depression: a pilot study

Abstract: Objective: Transcranial magnetic stimulation is an emerging treatment of treatmentresistant depression. Current protocols rely on daily treatments. This study was designed to determine whether the time period over which treatment is delivered is an important factor in efficacy.Method: Sixteen adult patients with treatment-resistant major depression were randomly assigned to one of the two treatment groups, both of which received 2 weeks of treatment. One group received daily treatment (10 treatments, on business days). The other group received three treatments in week one, and two treatments in week two (five treatments, on spaced business days). Mood was rated using the Hamilton Depression Rating Scale (HDRS) and a self-rated visual analogue scale. Response was defined as a 50% reduction in HDRS rating, and remission was defined as achieving an HDRS score of 8 or less. The groups were compared throughout the 2-week study period.Results: At entry, there were no demographic differences between the groups. ...

Quetiapine plus SSRI in treatment-resistant depression: possible mechanisms

Abstract: Depression is one of the most common illnesses and is very debilitating, but unfortunately, its treatment remains unsatisfactory. Despite adequate and optimum therapeutic interventions, only about 70% show a response to treatment and only about 40% reach full remission (Cowen 1996; Chehil et al. 2000). Up to 30% of patients fall into the category of treatment-resistant depression (TRD), which is defined as lack of response to adequate trials (optimum dose and duration) of two antidepressants of different classes (Cowen 1996; Chehil et al. 2000; Dursun et al. 2001; Devarajan and Dursun 2005). A wide range of factors including review of diagnosis, co-morbidity, optimization of medications, establishment of compliance, combination, augmentation, switching strategies and other non-pharmacological treatments need to be assessed prior to categorizing the depressed patient as being resistant to treatment. However, there are no established guidelines as there are no head-to-head trials of effectiveness that govern switching, augmenting, or combining strategies. Atypical antipsychotics (A-APs) in combination with SSRI (e.g., olanzapine plus fluoxetine; olanzapine plus venlafaxine) have been shown to be effective in TRD (Shelton et al. 2001; Devarajan and Dursun 2005). However, precise mechanism of action of this augmentation remains unclear. Furthermore, it remains to be determined whether efficacy of A-APs in TRD is a general class effect or to a specific A-AP. We, therefore, present a naturalistic and case series outcome of patients with non-psychotic TRD, treated with the combination of sertraline (SSRI) and quetiapine (an A-AP). Six consecutive patients suitable for the combination treatment were assessed and followed up (Table I). Past psychopharmacological history indicated that all patients were tried on optimum dose and duration of a tricyclic antidepressant and some had augmentation with lithium or bupropion. All patients initially received sertraline monotherapy and commenced on quetiapine after 6 to 8 weeks because of lack of significant effectiveness and unsatisfactory clinical response. Patients preferred to take quetiapine as a single dose at night to avoid daytime sedation. Both medication doses titrated gradually according to clinic response and tolerability over 2 weeks. Sertraline treatment had minimum effect on the baseline Hamilton Depression Rating Scale-21 item (HAM-D21) scores; however, adding quetiapine has improved the ratings and outcome (5– 6 weeks) (Table I). The adverse effects, which included dizziness, headache, dry mouth, and sedation, were mild and tolerable. Weight gain was not reported as an adverse effect. None of the patients reported, nor have we observed, any extrapyramidal side effects, or any other serious side effects including cardiovascular side effects. Olanzapine in combination with SSRI or venlafaxine has been shown to be effective in TRD (Shelton et al. 2001; Devarajan and Dursun 2005). Our preliminary and open data indicate that quetiapine may similarly augment SSRIs in TRD, which requires a randomized controlled trial data for confirmation of such effectiveness. Although the underlying mechanisms remain unclear, it is very unlikely that quetiapine’s augmentation of efficacy of sertraline is due to a pharmacokinetic interaction. The major metabolic pathway of quetiapine is sulfoxidation and CYP450-3A4 is the primary enzyme responsible for CYP-mediated metabolism (Li et al. 2005). Sertraline is characterized by weaker inihibition of CYP450 enzymes and, therefore, holds less potential for interaction with quetiapine (Naranjo et al. 1999). S. Devarajan Department of Psychiatry, University of Western Ontario, Ontario, Canada

Vagus nerve stimulation therapy in a patient with treatment-resistant depression: a case report of long-term follow-up and battery end-of-service.

Abstract: This is the first case report of a patient who received long-term (69-month) adjunctive vagus nerve stimulation (VNS) therapy for treatment-resistant depression (TRD) and reached VNS battery end-of-service (EOS). The patient is a 41-year-old female with depression who entered a study of adjunctive VNS therapy for TRD. Her Hamilton Rating Scale for Depression (HAM-D) scores dropped from a mean of 33.5 (pre-implantation baseline period) to 16 at the end of the 12-week acute-phase treatment period, and then fluctuated from <7 (normal range) to scores in the moderately depressed range (approximately 20) during long-term follow-up. Three and one-half years after VNS implantation, the patient's HAM-D scores began to increase from a score of 18 to a peak score of 27 approximately 16 months later (5-years post-implantation). The patient subsequently reported that she could no longer feel stimulation from the device and device interrogation 2 weeks later indicated battery EOS. The patient was hospitalized due to worsened depression, the pulse generator was replaced, and medication adjusted. HAM-D scores through the subsequent 9 months of follow-up returned to a pattern of fluctuations within the range noted during the long-term follow-up period prior to VNS battery EOS.

Vagus nerve stimulation and deep brain stimulation for treatment resistant depression.

Abstract: Neurostimulation techniques are potentially useful options for severely depressed patients who have failed trial after trial of medication and psychotherapy. Cervical VNS therapy for chronic or recurrent depression which does not resolve with pharmacotherapy was recently approved by the FDA. DBS for severe intractable depression has been studied in two pilot studies with very few patients to date. Further investigations are currently underway in order to more fully evaluate both of these neurostimulation therapies, with the hope of substantially improving the treatment of refractory depression.

Combination pharmacotherapy in unipolar depression.

Abstract: It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

How should you manage a depressed patient unresponsive to an SSRI

Abstract: The best approach among studied alternatives to manage a patient with treatment-resistant depression is not clear from the evidence. All of the options reviewed seem to have about a 25% to 30% success rate. Switching to other antidepressants or augmenting with non-antidepressant drugs has the best supporting evidence (strength of recommendation [SOR]: B).1 Adding additional antidepressants (SOR: B), using psychotherapy (SOR: B), and initiating electroconvulsive therapy (ECT) (SOR: C) are options. Various antidepressants are used as add-on therapy. Psychotherapy is often recommended, though the evidence of benefit after a failed course of initial therapy is sparse. The evidence supporting use of ECT in treatment-resistant depression is weak. Comparison among the options is based on expert opinion (SOR: C). Additional reports from the STAR*D trial may improve the quality of the evidence in the near future.