Magazine article Clinical Psychiatry News

Resistant Depression Research Isn't Being Followed. (Do as I Say, Not as I Do')

Magazine article Clinical Psychiatry News

Resistant Depression Research Isn't Being Followed. (Do as I Say, Not as I Do')

Article excerpt

ALBUQUERQUE--The best-supported therapeutic strategies in treatment-resistant depression are paradoxically relegated to third-tier status, Dr. Michael J. Gitlin said at a psychiatric symposium sponsored by the University of New Mexico.

Meanwhile, the agents that surveys show are most often used by psychiatrists for treatment-resistant depression--stimulants, atypical antipsychotics, and combinations of antidepressants-have little to no support from well-controlled trials, added Dr. Gitlin, professor of clinical psychiatry and director of the Mood Disorders Clinic at the University of California, Los Angeles, Neuropsychiatric Hospital.

So much for evidence-based medicine.

But Dr. Gitlin views this situation as less an indictment of the way his colleagues practice their craft than a criticism of marked deficiencies in the state of psychopharmacologic research. The key studies needed to rationally guide practice in the area of treatment-resistant depression simply haven't been done.

By far, the best-studied interventions involve the use of adjunctive agents. These aren't antidepressants, but they help antidepressants to work better. The adjunctive agents with far and away the strongest support from controlled trials are lithium and T3. Lithium's use as an adjunct in treatment-resistant depression is supported by no fewer than nine double-blind randomized trials and a positive metaanalysis, while T3 is supported by four double-blind trials.

So where do lithium and T3 fit into real-world practice? Basically they fit in as an afterthought. Surveys of the roughly 700 psychiatrists from all over the country who attend Massachusetts General Hospital's annual psychopharmacology course in Boston indicate that in depressed patients unresponsive to selective serotonin reuptake inhibitor (SSRI) therapy, most practitioners use lithium and T3 as third-line options, a category to which valproate and tricyclic antidepressants are also relegated.

The most common first-line strategy among practicing psychiatrists is to add buproprion (Wellbutrin) or stimulants to the SSRI. If that doesn't work or isn't an option, the prevailing second-tier strategy is to add mirtazapine (Remeron), buspirone (BuSpar), or an atypical antipsychotic agent to the SSRI.

Moreover, published surveys of the practices of psychiatric faculty at Harvard University Boston, indicate that they, too, shun lithium and T3 in treatment-resistant depression, preferentially resorting instead to antidepressant combinations, for which there are no supporting double-blind data.

"When I poll my UCLA psychopharmacology colleagues informally we do the same thing. All of us use combinations and stimulants as our first and second line, with lithium and T3 way down the road. Patients don't like lithium because of the weight gain, tremors, and need for blood tests, and none of us think T3 works very well. It's benign, it's easy to use, but it doesn't seem to work as well as stimulants or combinations," the psychiatrist said.

"The people writing the review articles don't do what they write in their review articles," Dr. Gitlin continued. "This is an example of classic bad parenting: 'Do as I say not as I do.' Nobody talks in these treatment-resistant depression articles about the fact that the docs are not doing what the double-blind literature shows. …

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