Management of Treatment-Resistant Depression: Challenges and Strategies

Summary & key facts

This paper is a careful review of research about treatment-resistant depression, which means major depression that does not get better after usual treatments. The authors searched medical literature to gather trials and reviews. They explain that experts do not all agree on one definition, but most models call it a poor response after at least two antidepressant trials. The review looks at many options people try when standard treatments fail — extra medicines added to antidepressants, switching drugs, several kinds of brain-stimulation treatments, psychotherapy, and newer approaches such as ketamine, psilocybin, and anti-inflammatory drugs — and concludes that bigger, better studies are sti

Key facts:

• Treatment-resistant depression is usually defined in research as depression that has not improved after at least two adequate trials of antidepressant medication.
• The authors did a PubMed search and assembled existing meta-analyses, clinical trials, and review papers to summarize the evidence on this topic.
• There is no single agreed definition or staging system for treatment-resistant depression, and that lack of agreement makes comparing studies and choosing treatments harder.
• Pharmacological strategies reviewed include adding medicines such as lithium, triiodothyronine (a thyroid hormone), and newer antipsychotic drugs, or switching the person to a different class of antidepressant.
• The review covers several brain-stimulation therapies, described as somatic treatments, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, and deep brain stimulation.
• The authors also summarized psychotherapies and novel treatments that are being studied, including ketamine, psilocybin, and anti-inflammatory drugs.
• Overall, the review finds that current evidence is still incomplete and calls for larger, well-designed studies to figure out the best treatment pathways for people with treatment-resistant depression.

Abstract

Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD.

Topics

Electroconvulsive Therapy Studies Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Antidepressant Anxiety Bipolar disorder Brain stimulation Deep brain stimulation Depression (economics) Disease Economics Electroconvulsive therapy Intensive care medicine Internal medicine Lithium (medication) Macroeconomics Major depressive disorder Medicine Modalities Mood Parkinson's disease Psychiatry Psychology Psychotherapist Schizophrenia (object-oriented programming) Social science Sociology Stimulation Transcranial magnetic stimulation Treatment-resistant depression Vagus nerve Vagus nerve stimulation

Substances

Ketamine Psilocybin

Conditions & symptoms

Anxiety Depression Lack of energy or motivation Poor sleep Sadness or low mood