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Lifestyle interventions for treatment-resistant depression

Introduction There are several common circumstances in which treatments outside the traditional Western Allopathic medical tradition can be useful for patients with treatment-resistant depression (TRD). While many patients benefit only partially from maximized medication and psychotherapy and desire additional evidence-based recommendations, a holistic approach has other advantages. First, many patients request alternative and complementary treatments with a goal of avoiding or reducing pharmacological therapies and their…

Treatment-resistant depression in pregnancy, the postpartum period, and transition to menopause

Introduction The lifetime risk for depression is greater in women than men ( ) and is especially high during female reproductive events including the perimenstrual, peripartum, and perimenopausal phases. The increased depression prevalence in women during reproductive transitions is hypothesized to be due to psychological, social, and physiological changes including the unique temporal hormonal fluctuations associated with each transition. Treatments available for women suffering from depression…

Managing treatment resistant depression in primary care settings

Scope of problem Major Depressive Disorder (MDD) is a common, often recurrent or chronic illness associated with significant morbidity. According to the World Health Organization, an estimated 4.4% of the global population suffers from depression. MDD is among the five leading causes of years lived with disability (YLDs) in 2016 ( ). Past-year depression prevalence increased significantly in the United States (U.S.) from 2005 to 2015…

Chronotherapeutics for treatment-resistant depression

Introduction According to the World Health Organization (WHO), bipolar or unipolar depression is the leading cause of ill health and disability worldwide. Depression affects nearly 20% of the population with an increase of more than 18% having been observed between 2005 and 2015 (WHO: WHO | Depression [Internet]. Depression. 2019). Depression is associated with a reduced quality of life, with the WHO predicting several years ago…

Drugs under investigation for treatment-resistant depression

Medications targeting the hypothalamic–pituitary–adrenal (HPA) axis Dysfunction in the hypothalamic–pituitary–adrenal (HPA) axis is one of the most well-established biological alterations in psychiatry ( ). The first observations of an elevation in basal cortisol levels in patients with depression were made almost half a century ago by Board and colleagues ( ) and multiple pieces of evidence contributed to this idea, including the role of stress in…

Inhaled gases for treatment-resistant major depression

Acknowledgment Special thanks to Britt Gott, MS, for her editorial input and assistance with the compilation of this chapter. Introduction Fortunately, most individuals who suffer from major depressive disorder (MDD) respond to first-line antidepressant treatments [pharmacotherapy and psychotherapy; ( ; )]. Over the course of the past 20 years, there has been increasing awareness that a significant subset of patients suffer from a more virulent form of…

Managing treatment-resistant depression in the setting of chronic pain

Among the many challenges of treating depression are the complications that arise when the depression is concurrent with other medical conditions. Not surprisingly, when a patient has two conditions, insufficient treatment of one condition may worsen the presentation or treatment outcome of the second condition. This is particularly true when dealing with concurrent mood problems and pain problems. Such complications arise from the bidirectional relationship between…

Managing treatment-resistant depression with comorbid substance use disorders

Introduction Overview: Double-trouble Substance use disorders (SUDs) and depressive disorders, including major depressive disorder (MDD), dysthymia, and substance induced mood (depressive) disorder (SIMD) are among the most prevalent psychiatric disorders in the world ( ; ). Not only are both independently common in the general population, they frequently cooccur in patients leading to challenges in assessment, differential diagnosis, treatment, and clinical management. Therefore, this chapter will…

Managing treatment-resistant depression with comorbid personality disorders

Personality disorders are some of the most common comorbid psychiatric conditions in major depressive disorder (MDD). The combination of MDD and personality disorders provides a real challenge to clinicians, as treatment of patients with these comorbid conditions is hampered by significant deficits in psychosocial and interpersonal functioning, often leading to poorer outcomes and treatment resistance. This chapter explores the relationship between personality disorders and TRD by…

Identification and management of anxious depression in patients with treatment-resistant depression

Part I: Identification Depression is a debilitating illness. The World Health Organization reports that globally 264 million people of all ages suffer from depression. The National Institute of Health reports that about 7% of all adults in the United States experience at least one episode of depression in their lives. Although depression is a treatable illness, access to treatment can be limited due to several factors…

Treatment-resistant depression in geriatrics

Introduction There has been a considerable increase in the number of older individuals in the United States, with those over the age of 85 representing the fastest growing segment of the population ( ). The global population has also seen an increase in the proportion of older individuals, especially among developing countries ( ). We must appreciate this demographic change by recognizing the many biopsychosocial elements…

Treatment-resistant depression in children and adolescents

Introduction Treatment-resistant depression in children and adolescents is defined as clinically significant depression that has not responded to treatment with a selective serotonin reuptake (SSRI) for at least 8 weeks by the TORDIA (Treatment of SSRI-Resistant Depression in Adolescents) trial ( ). define treatment-resistant depression in youth as clinically significant depression that fails to respond to an adequate treatment trial of one evidence-based antidepressant or one…

Treatment-resistant bipolar depression

Introduction Depressive symptoms are present during almost 70% of the symptomatic period in bipolar disorder patients (BD) ( ). Overall, patients with BD spent more than one-third of the time with subsyndromal or syndromal depression (17.6% and 18.4%, respectively, for BD type I; 17.8% and 19.1%, respectively, for BD type II) ( ). Depression in BD is also highly associated with suicidality. did a systematic review…

Evidence-based psychotherapy for treatment-resistant depression

Disclosures Dr. Jesse Wright is an author of the Good Days Ahead (GDA) computer program used in an investigation cited in this article, has an equity interest, and serves as a consultant to Mindstreet, Inc. developer and distributors of GDA. His conflict of interest is managed with an agreement with the University of Louisville. He receives book royalties from American Psychiatric Publishing, Inc., Guilford Press, and…

Treatment-resistant psychotic depression

Introduction Major depressive disorder with psychotic features, or psychotic depression, is a serious psychiatric illness that presents with a combination of depressed mood and psychosis. The psychosis commonly manifests through nihilistic-type delusions with overly self-critical beliefs, severe guilt, paranoia, and the belief that bad things are about to happen ( ; ; ). Psychotic depression is considered a more severe form of depression with increased symptomatology,…

Other neurosurgical interventions for treatment-resistant depression

Acknowledgments Interventional Psychiatry Program in the Department of Psychiatry and Behavioral Science at the University of Minnesota. Introduction The use of somatic interventions to control or treat mental symptoms dates back to ancient times ( ; ; ). Evidence for burr holes drilled into the skull to “cure the demons” goes back to the Neolithic age. The notions that convulsions and fever may help mental disorders…

Deep brain stimulation for treatment-resistant depression

Introduction Neurosurgical interventions for the treatment of psychiatric illnesses have been used since the dawn of the somatic treatments in neuropsychiatry ( ). The use of surgery in psychiatry existed before there were effective pharmacological strategies, such as antidepressants or antipsychotics ( ). Egas Moniz, a Portuguese neurologist, partnered with neurosurgeon Almeida Lima to perform a frontal leucotomy in 1935 in a 63-year-old woman suffering from…

VNS for treatment-resistant depression

History Interest in the effects of vagus nerve stimulation (VNS) on the central nervous system began in the early 20th century, with Bailey and Bremer demonstrating in 1938 that electrical stimulation of the vagus nerve of cats resulted in increased electrographical activity of cortical structures ( ). Dell and Olson discovered a suggestive link between the vagus nerve and affective disorders in 1951 in their own…

MST for treatment-resistant depression

Introduction Magnetic seizure therapy (MST), as the name implies, is a treatment that involves the induction of therapeutic seizures generated through magnetic fields. The impetus for developing this treatment was the goal of achieving comparable therapeutic effects to ECT, while minimizing its cognitive side effect profile. ECT is known to be a highly effective treatment for treatment-resistant depression (TRD) ( ), and this is reviewed in…

ECT for treatment-resistant depression

Introduction Electroconvulsive therapy (ECT) is the oldest biologic treatment in psychiatry still in use and continues to play a crucial role in the management of treatment-resistant depression (TRD). ECT has been shown to be significantly more effective than pharmacotherapy in the management of TRD, with many studies citing remission rates of 50%–60% compared to 10%–40% with further medication adjustments ( ; ; ). Rates of remission…