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MDDA-Boston Lecture Series

TREATMENT-RESISTANT DEPRESSION
Highlights of a lecture by Scott Aaronson, M.D., psychiatrist in private practice, Newton Centre, MA.
Wednesday, March 22, 2000

While Dr. Aaronson's talk was billed as about treatment-resistant depression, to many MDDA members it came across as a helpful review of standard treatments for depression combined with some interesting insights into new means of combatting the illness.

Treatment Resistant Depression Defined

Dr. Aaronson defined treatment-resistant depression as the failure to respond to an adequate trial of an anti-depressant. In his current study, he defines it as people who have failed to respond to seratoninogenic meds ( (40 mg of Prozac, 150 mg of Zoloft, 40 mg of Celexa, or 40 mg of Paxal) for at least 4 weeks.

In Dr. Aaronson's opinion, if a someone with depressive illness does not respond to a medication within 6 weeks, there is a good probability they will not respond in 12 weeks. The exception to this is when the person has OCD,or Obsessive-Compulsive Disorder, when improvement can occur further into the course of treatment.

The doctor pointed out that the distinction between partial response versus no response is critical in determining the future course of treatment. With a partial response, he is more likely to supplement the existing med with something else. With patients exhibiting no response, it is best to take the patient off the medication completely rather than give them more of the same.

1980s: Treatment Resistant = Inadequate Treatment

Dr. Aaronson's review of the history of depression treatment began in the 1980s when inadequate treatment was the biggest cause of treatment-resistant depression. MAO inhibitors were the anti-depressant drug of choice at the time, and in many cases patients' medication levels were simply insufficent for them to respond.

Broad Spectrum versus Narrow Spectrum Treatment

Dr. Aaronson pointed out the distinction between treatment with broad spectrum medications versus narrow spectrum. This relates to whether the medication works on (typically) the reuptake one or many neurotransmitters, such as seratonin, dopamine, or norepinephrine. He tends to start treatment with narrow spectrum meds like SSRIs (Prozac, etc.) versus broad spectrum, working up to broad spectrum medications if needed. Prompted by a question from an MDDA member, Dr. Aaronson did point out that, particularly with the SSRIs, the patient may experience an inital impressive brisk response that wears off over time and can't be replicated.

As part of this portion of the talk he gave a review of the standard anti-depressant medication classes: the SSRIs (Prozac, Xoloft, etc. that block seratonin reuptake), Wellbutrin, which is a both a norepinephrine and dopamine reuptake inhibitor, Serazone and Trazedone, which each have their own modes of action, and Effexor.

Effexor has qualities of both a broad spectrum and narrow spectrum medication, in that in low doses it works like a narrow-spectrum SSRI. In higher doses it begins to act like a broad spectrum medication by blocking norephinephrine uptake, then in even higher doses blocks dopamine reuptake. MAO inhibitors are also considered a broad spectrum treatment.

While many of the anti-depressants out on the market now block reuptake of neurotransmitters, Remeron actually increases the release of chemicals in the brain. It also has an anti-histamine-like effect that can put people to sleep. In his practice, Remeron is usually used in combination with other medications.

Dr. Aaronson also pointed out that there is increasing interest in glutamate action, although these meds are usually anti-convulsants and not anti-depressants. Lamictal is a glutamate-enhancing drug.

Poly-Pharmacy: Supplementing The Anti-Depressants

Poly-pharmacy is the practice of using several different meds to treat depression or other ailments. Supplementing anti-depressants with the new atypical psychotics, such as Zyprexa and Seraquel, is currently the focus of one of Dr. Aaronson's studies. He reported a lot of success with supplementing anti-depressants with these new anti-psychotics, and gave the example of a depressed patient whose suicidal ideation was not relieved until they were placed on Zypreza, in spite of the prior use of several different anti-depressants.

Supplementation with mood stabilizers has been going on for some time, and lithium augmentation has been practiced for a long time. All of the anti-epileptics used for mood stabilization are also considered, and he finds that Lamictal supplementation works well with cyclical depression, although some patients are subject to rashes as a result of taking it. Omega 3 fatty acids are also being used to supplement anti-depressants with some success.

New Meds In The Pipeline

Dr. Aaronson gave a short review of new medications currently being worked on but not yet available for use. A new category of medications, substance P inhibitors, is beting worked on by a number of the pharmaceutical companies. He also mentioned the new anti-depressant Roboxatine that should be released within the next year by Pharmacia Upjohn. This medication is considered a pure norepinephrine reuptake blocker.

From the endocrinology side, a new class of CRF blockers is currently in Phase II clinical trials. These CRF (corticotropin releasing factor) blockers block release of stress hormones that may contribute to depression.

One of our MDDA members asked Dr. Aaronson about Mirapex (sp?), another new medication considered for depression. Dr. Aaronson replied that Mirapex may be considered as a 3rd or 4th level treatment for extremely resistant depression, but that the medication had lots of side effects. Mirapex is a medication used for Parkinson's Disease that has a dopamine action.

ECT Still The Gold Standard, But Maintenance An Issue

Dr. Aaronson still considers ECT to be the gold standard for relieving depression, but pointed out that then the practitioner is faced with the task of keeping the patient out of depression. He does not believe in maintenence ECT. If ECT doesn't work after a few rounds, he will look elsewhere for treatment. In general he tends to refer only 2 or 3 patients a year for ECT.

This lecture summary is provided as a service to MDDA members as well as our friends and supporters. Please consider donating to MDDA or becoming a member to assist us in providing continued information about affective disorders and their treatment.

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