Major depressive disorder: Validated treatments and future challenges

Depression is a prevalent psychiatric disorder that often leads to poor quality of life and impaired functioning. Treatment during the acute phase of a major depressive episode aims to help the patient reach a remission state and eventually return to their baseline level of functioning. Pharmacotherapy, especially selective serotonin reuptake inhibitors antidepressants, remains the most frequent option for treating depression during the acute phase, while other promising pharmacological options are still competing for the attention of practitioners. Depression-focused psychotherapy is the second most common option for helping patients overcome the acute phase, maintain remission, and prevent relapses. Electroconvulsive therapy is the most effective somatic therapy for depression in some specific situations; meanwhile, other methods have limits, and their specific indications are still being studied. Combining medications, psychotherapy, and somatic therapies remains the most effective way to manage resistant forms of depression.     

Use of Electroconvulsive Therapy With Children: An Overview and Case Report

TOPIC. Electroconvulsive therapy (ECT) has become more common in the treatment ofadults with refractory mood disorders and psychotic disorders but it remains one of the least common therapies for mental illness in children. In a small number of child psychiaty cases, symptoms are severe and unresponsive to standard pharmacological and other therapies. With these patients, ECT might be helpful.
PURPOSE. This article provides an overview of ECT, indications for its use and a case report that illustrates the successful use of ECT with an 8-year-old girl with psychotic depression. Implications for multidisciplinary care are discussed, including preparation of the patient and family, assessment of response to ECT, management of adverse effects, preparation for discharge and discharge care.
SOURCES. Existing literature on the use of ECT in adults, adolescents, and children and the clinical experience of providing care to an 8-year-old patient on an acute care inpatient unit.
CONCLUSIONS. Nurses and other healthcare personnel should consider ECT in refractory cases of major depressive disorder, bipolar affective disorder, schizophrenia, and other psychotic disorders.     

ECT in an Adolescent with Down Syndrome and Treatment-Refractory Major Depressive Disorder

The efficacy of electroconvulsive therapy (ECT) as a treatment for patients with major depressive disorder who are intolerant of or refractory to antidepressant medications is well known. This treatment may be overlooked in children and adolescents, and in those with developmental disabilities. The case report of a 15-year-old male with Down syndrome and treatment-refractory major depressive disorder who received ECT is presented. Four bilateral ECT treatments resulted in a substantial improvement of the patient's depressive symptoms. In this case, ECT was a safe and effective treatment for an adolescent with Down syndrome. Although no generalization can be based on a single case report, when appropriate, ECT should be considered as a treatment for this patient population.     

Electroconvulsive therapy in patients with cardiac pacemakers and implantable cardioverter defibrillators

Electroconvulsive therapy (ECT) is used to treat major depressive illness, especially in elderly and medically frail patients. Not uncommonly, these patients have cardiac pacemakers or implantable cardioverter defibrillators (ICDs). Only a few case reports in the literature describe the use of ECT in such patients. Herein we review our ECT experience treating 26 pacemaker patients and 3 ICD patients. All patients obtained significant antidepressant benefits with ETC. Only one serious cardiac event occurred, a case of supraventricular tachycardia (SVT) requiring a stay on the cardiac intensive care unit. The SVT resolved and the patient went on to receive further uncomplicated ECT treatments. We conclude from this experience that with proper pre-ECT cardiac and pacemaker/defibrillator assessment, ECT can be safely and effectively administered to patients with an implanted cardiac device.     

Rational use of antidepressants

The key to the proper treatment of affective illness is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the tricyclic antidepressants for a major depressive episode, electroconvulsive therapy for a major depressive episode with psychotic features, and monoamine oxidase inhibitors for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy or ECT. Second-generation antidepressants are recommended in situations where their adverse effect profiles offer significant advantages over TCAs in an individual patient. Maintenance antidepressant treatment may be necessary to prevent recurrent depressive episodes.     

低频重复经颅磁刺激治疗重性抑郁障碍有效性和安全性的系统评价

目的系统评价低频重复经颅磁刺激(低频rTMS)治疗重性抑郁障碍的效果。方法计算机检索Cochrane图书馆、MEDLINE、EMbase、CBMdisk、CNKI、VIP等数据库,收集1985～2011年国内外关于低频rTMS作用于右侧额叶背外侧皮质治疗重性抑郁障碍的随机对照试验(RCT)。由两位研究者独立提取资料和评价纳入研究质量后,采用RevMan 4.2软件进行Meta分析。结果共纳入7个随机双盲对照试验,包括234例重性抑郁障碍患者。质量评价结果显示,7个研究中A级1个,B级5个,C级1个。Meta分析结果显示:治疗2周后,低频rTMS组的临床治愈率显著高于假刺激组[RR=3.11,95%CI(1.56,6.19)],而HDRS评分和MADRS评分则显著低于假刺激组[WMD=–6.41,95%CI(–9.32,–3.50);WMD=–5.27,95%CI(–9.08,–1.46)],但有效性与假刺激组无显著差异[RR=1.72,95%CI(0.74,4.01)]。7个纳入研究均未报道任何严重、不可耐受的不良反应。结论低频rTMS是一种无创、安全的治疗技术,可提高重度抑郁障碍患者的临床治愈率,降低抑郁量表评分,但有效率与假刺激组无显著差异。建议进行重性抑郁障碍治疗时,rTMS的参数选择:频率为1Hz,强度为运动阈值的90%～110%,作用位置右侧额叶背外侧区,治疗周期2周。但在将其应用到临床一线治疗之前,仍需开展更多大样本多中心的高质量研究。     

Electroconvulsive therapy of depressive disorders

Electroconvulsive therapy (ECT) is the most effective treatment in all types of major depression. On the other side ECT has long suffered from controversial public image, a reputation that has effectively removed it as treatment option for many patients. Today ECT is an effective and safe treatment for those with severe mental illness. Electroconvulsive therapy has undergone fundamental changes since its introduction 65 years ago. It is no longer a memory-modifying, fearsome treatment pictured in films. Anesthesia, controlled oxygenation, and muscle relaxation make the ECT so safe that the risks are less as those which accompany the use of several psychotropic drugs. Indeed, for the elderly, the systematic ill, and pregnant women, electroconvulsive therapy is a safer treatment for mental illness than any alternative.     

Electroconvulsive therapy in the management of chronic pain

Electroconvulsive therapy (ECT) is used predominantly to treat major depressive illness but has also been used for chronic pain. ECT causes a variety of neurochemical and neurophysiologic effects, some of which may interact with the pathophysiologic mechanisms in complex pain states. An extensive literature on the use of ECT in pain patients identifies subgroups for whom ECT may result in substantial pain relief. In this article, we review the literature on the use of ECT in pain patients, suggest possible neurobiologic bases for the efficacy of ECT in such patients, and conclude with our recommendations for current clinical practice.     

Improving medication compliance in patients with depression: Use of orodispersible tablets

The treatment of major depressive disorder requires prolonged pharmacotherapy with antidepressants in order to resolve the current episode and reduce the risk for recurrence of depressive symptoms. Such prolonged therapy requires considerable commitment on the part of patients to take their medication as prescribed. Medication compliance is often poor among psychiatric patients, including those with major depressive disorder; this can result in poor long-term outcomes and, ultimately, treatment failure. The onus lies with the prescribing physician to support patients in complying with their medication regimen. Establishing and maintaining a supportive therapeutic relationship is an essential foundation for ensuring patient compliance. Difficulty in swallowing conventional tablets and capsules has emerged as an additional factor in medication noncompliance and has led to the development of alternative drug delivery strategies such as orodispersible tablets (ODTs). ODTs are associated with improved medication compliance compared with traditional tablet formulations. An ODT formulation of the antidepressant mirtazapine has been available since 2001 and an ODT formulation of escitalopram is currently in development. Such formulations offer convenient alternatives to traditional tablets and may support patient compliance with extended therapy. This review discusses practical methods of improving compliance in patients with depression with a particular focus on ODTs.     

Electroconvulsive therapy: a review of history, patient selection, technique, and medication management

Electroconvulsive therapy (ECT) is a safe and effective treatment for severe and persistent depression, bipolar disorder and schizophrenia. Though ECT is now over 60 years old, it remains an underutilized treatment today. History, patient selection, safety, and characteristics of the treatment stimulus, technique, and medications used in ECT are reviewed. Dosing strategies, as pertaining to seizure threshold, will be considered. Mechanisms of action, especially with regard to serotonin, norepinephrine, and dopamine receptor expression will be discussed.     

Treatment of major depressive disorder--method and selection of the treatment

There are many ways of treatment for depression. Among them the most popular and effective treatment is pharmacotherapy. In the acute phase, pharmacotherapy with antidepressants, certain forms of psychotherapy, the combination of pharmacotherapy plus psychotherapy, and electroconvulsive treatment have clearly proven to be efficacious in most types of unipolar depressive disorders. The common augmenting agents probably are lithium, thyroid hormone, dopaminergic agents, and mood stabilizers. Certain treatments may be more effective in specific subtypes; for example, light therapy is useful for seasonal affective disorder. During the 16-24 weeks following remission, patients with antidepressant medications in the acute phase should be maintained on these agents to prevent relapse. For patient pharmacotherapy or psychotherapy has not been effective, the use of ECT may be useful. Following the continuation phase, maintenance-phase treatment should be considered for patients who have many depressive episodes to prevent recurrences of major depressive disorder.     

Strategies for treatment-resistant depression

Clinical depression is a common disorder with serious implications that is often misdiagnosed or underestimated. More than 50% of suicides are associated with a major depressive disorder, and depression can adversely impact a variety of other medical conditions. Although > or = 70% of depressions can respond to appropriate medications, few patients actually receive adequate medical therapy. This article reviews the definition of adequate therapy for depression, discusses common comorbid conditions, and examines the issue of true treatment resistance. Practical strategies for treatment-resistant depression, including switching classes of antidepressant drugs, combination therapy, augmentation strategies, and somatic therapies, are incorporated into a treatment algorithm.     

Other treatments for depressive patients

Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT.     

Integrating psychotherapy and pharmacotherapy for treatment of major depressive disorder. Current status and future considerations

The treatment of depression with psychotherapy and pharmacotherapy is one of the best-studied areas, yet much controversy exists about the relative merits of these treatments, singly and in combination. The author suggests that a combination of these therapies is not routinely indicated for uncomplicated major depressive disorder and provides some examples in which combined therapy can have a profound and cost- effective impact.     

Electroconvulsive therapy as maintenance therapy and for prevention of recurrence in psychiatric disorders and Parkinson disease

Electroconvulsive therapy is a reliable and safe option for patients with psychiatric disorders who are resistant or intolerant to medication as these patients usually respond quickly to this form of treatment. For clinicians, the management of these often severely ill patients is an important challenge given the high rate of relapse of these disorders. Maintenance electroconvulsive therapy is an interesting treatment option for these patients. Until now, only few controlled studies exist about the long-term outcome of this treatment in depressive disorders and other psychiatric disorders. Altogether, this form of outpatient prophylactic therapy has been found to be safe, well tolerated, and efficacious in relapse prevention. Moreover, it has been found to reduce hospitalization rates. Particularly in the elderly, and in patients who have been shown to be refractory to medication regimens, maintenance electroconvulsive therapy should be seriously considered as a means to reduce the risk of recurrence of illness. In Parkinson's disease maintenance electroconvulsive therapy is not widely established although its usefulness has been documented in numerous studies. First-line evidence data on incidence, dimensions and outcome of cognitive side effects under maintenance electroconvulsive therapy is still warranted.     

Childhood and adolescent depression

Depression is a common, chronic and recurrent disorder in children and adolescents. This article reviewed the epidemiology, clinical characteristics, natural course and treatment (pharmacological and psychotherapeutic treatment) of major depressive disorder (MDD) in children and adolescents. Several randomized controlled trials have shown that the selective serotonin reuptake inhibitors (SSRIs), in particular fluoxetine, and psychotherapeutic treatments such as cognitive behavioral therapy and interpersonal therapy are efficacious in children and adolescents with MDD. However, in Japan only three SSRIs (fluvoxamine, paroxetine and sertraline) are currently available, and few clinicians are trained to deliver psychotherapeutic treatment. Further clinical researches on the treatment to children and adolescents with MDD are needed in Japan.     

Active versus receptive group music therapy for major depressive disorder—A pilot study

ObjectivesTo compare the effects of 1) active group music therapy and 2) receptive group music therapy to group counseling in treatment of major depressive disorder (MDD).Design & settingOn top of standard care, 14 MDD outpatients were randomly assigned to receive 1) active group music therapy (n = 5), 2) receptive group music therapy (n = 5), or 3) group counseling (n = 4). There were 12 one-hour weekly group sessions in each arm.Main outcome measuresParticipants were assessed at baseline, 1 month (after 4 sessions), 3 months (end of interventions), and 6 months. Primary outcomes were depressive scores measured by Montgomery-Åsberg Depression Rating Scale (MADRS) Thai version. Secondary outcomes were self-rated depression score and quality of life.ResultsAt 1 month, 3 months, and 6 months, both therapy groups showed statistically non-significant reduction in MADRS Thai scores when compared with the control group (group counseling). The reduction was slightly greater in the active group than the receptive group. Although there were trend toward better outcomes on self-report depression and quality of life, the differences were not statistically significant.ConclusionGroup music therapy, either active or receptive, is an interesting adjunctive treatment option for outpatients with MDD. The receptive group may reach peak therapeutic effect faster, but the active group may have higher peak effect. Group music therapy deserves further comprehensive studies.     

ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3–5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies.     

Arrhythmias associated with electroconvulsive therapy in hypertrophic cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) are inherently prone to arrhythmias. Electroconvulsive therapy (ECT), a well-known treatment in psychiatry, leads to a catecholamine surge and may cause arrhythmias in patients with severe coronary and valvular heart diseases and heart failure. Whether ECT is safe in HCM is unknown. We systematically investigated the effects of ECT on the arrhythmia profile and left ventricular outflow obstruction of a HCM patient by serial ambulatory Holter electrocardiograms and echocardiograms before and after ECT. Our observations provide insight into the evaluation and management of a HCM patient undergoing ECT.     

Assessment and treatment strategies for depressive disorders commonly encountered in primary care settings.

Frequently overlooked, depression is a very common complex disorder that causes significant morbidity and mortality. This article provides a review of three commonly encountered depressive disorders in primary care settings: adjustment disorder with depressed mood, dysthymia and major depression. Since many individuals minimize the affective symptoms of depression, clinicians must maintain a high index of suspicion when clients present with vague somatic complaints, such as fatigue, headache, constipation and difficulty sleeping. To reach an accurate diagnosis, a thorough history, physical examination and appropriate laboratory studies should be performed. Numerous rating scales are presented to aid assessment. Common intervention strategies for the treatment of depressive disorders include education, drug therapy, and supportive individual and family counseling.