Therapies for Treatment Resistant Depression

Therapies for Treatment Resistant Depression

Approximately 17% of individuals—nearly one out of five people— experience a major depressive episode during their lifetime. Many of these patients are unrecognized or receive inadequate treatment. A few definitions will help in understanding treatment-resistance:

Nonresponse—no clinically meaningful response. One-third of patients given one antidepressant will fail to show any meaningful improvement.

Partial response—25-50% improvement in symptoms.

Treatment response—50% or greater improvement in symptoms.

Remission—absence of virtually all psychopathology.

Inadequate epidemiological research obscures the number of patients who experience a partial response or a treatment response. Patients may be satisfied with a partial response because the think “this is as good as it can get.” The goal for all treatment, however, should be full remission.

A simple test can help the physician follow the response to treatment. The physician can ask,”On a scale of zero to ten with zero being the worst you have ever felt and 10 being the best you have ever felt, how would you rate yourself?” The goal—a nine or a ten following an adequate course of treatment. If the patient fails to progress the physician has several options to improve outcome:

1. Raise the dose of the antidepressant. Unfortunately some antidepressants have a flat dose-response curve, so after a certain dose has been reached, raising it will have no further effect on symptoms.
2. Switch to another antidepressant. Switching from an SSRI to a different type of agent may be effective. Switching from one SSRI to another may be effective as well.
3. Add psychotherapy. For mild to moderate depression, Cognitive Behavior Therapy has been show to be just as effective as antidepressant medication. CBT in combination with medication is powerful.
4. Switch to a dual-mechanism antidepressant. A decrease in the firing activity of noradrenergic locus ceruleus neurons has been noted after three weeks of SSRI administration. This action may explain why the SSRIs are effective treatments for anxiety disorders. This decrease may also explain why some depressed patients respond to dual-action antidepressants or augmentation with other agents.
5. Combine two antidepressants. Disadvantages of combination (and augmentation) include increased cost and decreased compliance.
6. Augment with another medication.

·      Add a second generation neuroleptic. Atypical antipsychotics may augment antidepressants by increasing norepinephrine activity.

·      Add a mood stabilizer. Depressed patients may have a bipolar disorder and the manic phase of the illness has not yet emerged.

7. Recommend ECT.  ECT remains the most effective treatment for severe depression but is seldom used because of stigma and misinformation.
8. Emerging therapies. Transcranial magnetic stimulation, vagus nerve stimulation and deep brain stimulation may prove effective.