Treatment-resistant depression: new therapies on the horizon.
Trivedi MH.
Ann Clin Psychiatry. 2003 Mar;15(1):59-70

Depression and Anxiety Disorders Program, The University of Texas, Southwestern
Medical School, Dallas, Texas, USA. madhukar.trivedi@utsouthwestern.edu

Managing patients with treatment-resistant depression (TRD) remains a major
challenge for the practicing physician. Depression is considered
treatment-resistant when at least two adequate monotherapy trials with drugs
from different pharmacologic classes fail to elicit a therapeutic response.
Although determining the stage of TRD may allow concise description of a
patient's antidepressant history, management of TRD is better served by recent
attempts to create a treatment algorithm that encompasses definitive diagnosis
of true TRD and strategies for optimizing available therapies, including
consideration of novel treatment options. Present strategies for managing TRD
include optimization of the initial drug, substitution of another drug from the
same or a different antidepressant class, combination of two antidepressants
with different mechanisms of action, and adding an antidepressant drug from
another class. Potential nonpharmacologic treatments include vagus nerve
stimulation, repetitive transcranial magnetic stimulation, and magnetic seizure
therapy as an alternative to electroconvulsive therapy. Several neuropeptides
and their receptors have also been identified as potential targets for
pharmacologic intervention, including corticotropin-releasing factor and
substance P. Other treatments currently under investigation include augmentation
of antidepressant therapy with an atypical antipsychotic agent such as
olanzapine or risperidone. This kind of therapeutic intervention may prove to be
especially useful in treating patients with TRD.

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