Evolving Refractory Major Depressive Disorder Diagnostic and Treatment Paradigms: Toward Closed-Loop Therapeutics

  title={Evolving Refractory Major Depressive Disorder Diagnostic and Treatment Paradigms: Toward Closed-Loop Therapeutics},
  author={Matthew P. Ward and Pedro P. Irazoqui},
  journal={Frontiers in Neuroengineering},
  • M. Ward, P. Irazoqui
  • Published 1 March 2010
  • Psychology, Medicine
  • Frontiers in Neuroengineering
Current antidepressant therapies do not effectively control or cure depressive symptoms. Pharmaceutical therapies altogether fail to address an estimated 4 million Americans who suffer from a recurrent and severe treatment-resistant form of depression known as refractory major depressive disorder. Subjective diagnostic schemes, differing manifestations of the disorder, and antidepressant treatments with limited theoretical bases each contribute to the general lack of therapeutic efficacy and… 

Tables from this paper

Treatment-resistant depression: therapeutic trends, challenges, and future directions
  • K. S. Al-Harbi
  • Psychology, Medicine
    Patient preference and adherence
  • 2012
Treatment-resistant depression continues to challenge mental health care providers, and further relevant research involving newer drugs is warranted to improve the quality of life of patients with the disorder.
Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients.
Neuromodulation therapies and treatment-resistant depression
NTs are promising in patients withTRD, as the majority of them show good clinical response measured by standardized depression scales, and need further technological refinements and optimization together with continuing well-designed studies that recruit larger numbers of participants with TRD.
Vitamin D: An Anti-Inflammatory Treatment Option for Depression?
Principal approaches to its management include novel antidepressants, adjunct second generation antipsychotic agents and mood stabilizers, evidence-based psychotherapies, and complementary and alternative therapies.
An investigation into closed-loop treatment of neurological disorders based on sensing mitochondrial dysfunction
A generic model of the closed-loop treatment is developed to describe the high-level functions of any system designed to control neural function based on mitochondrial response to stimulation, simplifying comparison and future meta-analysis.


Neurostimulatory therapeutics in management of treatment-resistant depression with focus on deep brain stimulation.
Although deep brain stimulation is the most invasive of the neurostimulatory treatments developed to date, it may hold significant promise in alleviating symptoms and improving the quality of life for patients with the most severe and disabling mood disorders.
VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms
Evidence from neuroimaging and other studies suggests that VNS therapy acts via innervation of the nucleus tractus solitarius, with secondary projections to limbic and cortical structures that are involved in mood regulation, including brainstem regions that contain serotonergic and noradrenergic regions that project to the forebrain.
Deep Brain Stimulation for Treatment-Resistant
It is suggested that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.
A Patient with a Resistant Major Depression Disorder Treated with Deep Brain Stimulation in the Inferior Thalamic Peduncle
Promising results of electrical stimulation of the inferior thalamic peduncle are presented to treat recurrent unipolar depression in a patient with resistant major depression disorder and borderline personality disorder who responded poorly to treatment.
Diagnosis and definition of treatment-resistant depression
  • M. Fava
  • Psychology, Medicine
    Biological Psychiatry
  • 2003
Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy.
Brain changes underlying response to CBT were examined using resting-state fluorine-18-labeled deoxyglucose positron emission tomography to examine changes associated with cognitive behavior therapy (CBT).
Carbamazepine in manic-depressive illness: a new treatment.
The authors evaluated carbamazepine (Tegretol), a drug of choice for treatment of temporal lobe epilepsy, in a double-blind placebo-controlled trial in patients with manic-depressive illness. Seven
Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment.
TMS was associated with a low incidence of adverse events that were mild to moderate in intensity and demonstrated a largely predictable time course of resolution, and may offer clinicians a novel, well-tolerated alternative for the treatment of major depressive disorder that can be safely administered in an outpatient setting.
The neurobiology of depression.
Prospective studies examining the interaction between changes in brain function and structure in relation to stress and identified relevant genes and how these may be influenced by antidepressant drug treatment and the long-term course of depression would help clarify their role in the pathophysiology of this disorder.