Strategies for Treatment-Resistant Depression: Lessons Learned from Animal Models

Around 300 million individuals are affected by major depressive disorder (MDD) in the world. Despite this high number of affected individuals, more than 50% of patients do not respond to antidepressants approved to treat MDD. Patients with MDD that do not respond to 2 or more first-line antidepressant treatments are considered to have treatment-resistant depression (TRD). Animal models of depression are important tools to better understand the pathophysiology of MDD as well as to help in the development of novel and fast antidepressants for TRD patients. This review will emphasize some discovery strategies for TRD from studies on animal models, including, antagonists of N-methyl-D-aspartate (NMDA) receptor (ketamine and memantine), electroconvulsive therapy (ECT), lithium, minocycline, quetiapine, and deep brain stimulation. Animal models of depression are not sufficient to represent all the traits of TRD, but they greatly aid in understanding the mechanism by which therapies that work for TRD exert antidepressant effects. Interestingly, these innovative therapies have mechanisms of action different from those of classic antidepressants. These effects are mainly related to the regulation of neurotransmitter activity, including general glutamate and increased connectivity, synaptic capacity, and neuroplasticity.Mol Neuropsychiatry
Source: Molecular Neuropsychiatry - Category: Neuroscience Source Type: research

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Depression affects 450 million people worldwide and 15 million adults in the United States (U.S.) alone. Suicide is the 10th leading cause of death in the United States, claiming over 40,000 lives every year. We see these heartbreaking stories making headlines too often, and there are tens of thousands more we do not know about. The scariest part? There is no end in sight. Antidepressants are one of the three most commonly used therapeutic drug classes in the United States. Approximately 1 in 9 Americans of all ages reported taking at least one antidepressant medication — a number that was less than 1 in 50 just th...
Source: Psych Central - Category: Psychiatry Authors: Tags: Antidepressants Bipolar Depression Medications Mood Stabilizers Neuroscience Suicide Treatment Deep brain stimulation Deep transcranial magnetic stimulation Depression Treatment Electroconvulsive Therapy Major Depressive Disorder Source Type: news
The antidepressant effects of ketamine appear to depend on activation of the brain ’s opioid receptors, underscoring the drug’s addictive potential, according to areport published today inAJP in Advance.The study, by Alan Schatzberg, M.D. (pictured left), the Kenneth T. Norris Jr. Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, and colleagues, found that when patients with treatment-resistant depression were treated with the opioid antagonist naltrexone before receiving an infusion of ketamine, the antidepressant effects of ketamine were dramatically diminished.“...
Source: Psychiatr News - Category: Psychiatry Tags: addiction antidepressant depression ketamine opioid receptors opioid system suicide Source Type: research
In this issue of the journal, 2 case reports are presented that illustrate explicit influences of structural brain lesions on psychiatric symptoms. In both cases, the patients had preexisting, classically diagnosed psychiatric disorders—schizophrenia in the first case and bipolar I disorder in the second case. In the first case, a 61-year-old woman with chronic paranoid schizophrenia experienced a marked reduction in psychotic symptoms after bilateral frontal strokes. In the second case, a 60-year-old man who had experienced manic and depressive episodes since his 20s developed partial complex seizures after having r...
Source: Journal of Psychiatric Practice - Category: Psychiatry Tags: Clinical Case Discussions Source Type: research
We describe their treatment and review the current literature on the use of ECT among patients with PD. CASE SERIES All six patients in our retrospective chart review received bitemporal modified brief pulse ECT. Prior to ECT, the patients underwent pre-ECT evaluation, which involved hemogram analysis, renal and liver function tests, fasting blood glucose analysis, chest X-ray (posteroanterior view), and serum electrolyte analysis, all of which were within the normal range for all six patients, and none of the patients showed evidence of raised intracranial pressure on fundoscopy examination. All patients provided written ...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Case Review Current Issue Depression Devices ECT Mental Disorders Mood Disorders Movement Disorders Neurology Parkinson's disease Psychiatry Technology Electroconvulsive therapy parkinson’s disease Source Type: research
Major depressive disorder (MDD) is a major international public health issue. The disorder is common and characterized by marked loss of quality of life years, financial burden and high mortality. Effective interventions include psychotherapy, antidepressant drugs, and electroconvulsive therapy (ECT). However, failure to respond to antidepressant treatment occurs in up to 30% of patients with MDD [1], with 52% of these pharmacotherapy resistant patients unresponsive to ECT. Such patients are categorized as having treatment-resistant depression (TRD) [2], which is associated with more frequent hospitalization, higher suicid...
Source: BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation - Category: Neurology Authors: Source Type: research
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Source: The Journal of ECT - Category: Psychiatry Tags: Letters to the Editor Source Type: research
Conclusions Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline.
Source: Brain Stimulation - Category: Neurology Source Type: research
Invasive and non-invasive functional neuromodulation techniques are increasingly applied to treat neurological and psychiatric disorders such as essential tremor, Parkinson ’s disease, chronic pain, severe depression and obsessive-compulsive disorders. The introduction of deep brain stimulation (DBS) for movement disorders, cortical stimulation for intractable pain or electroconvulsive therapy and repetitive transcranial magnetic stimulation (rTMS) for the therapy of severe depressions are the most illustrious clinical developments for the management of neurologic and psychiatric conditions beside pharmacological remedies.
Source: Clinical Neurophysiology - Category: Neuroscience Authors: Tags: Editorial Source Type: research
BACKGROUND: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery ...
Source: SafetyLit - Category: Global & Universal Tags: Economics of Injury and Safety, PTSD, Injury Outcomes Source Type: news
Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe...
Source: BMC Psychiatry - Category: Psychiatry Authors: Source Type: research
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