Major Depressive Disorder

Combo of Drugs Can Help Treatment-resistant Depression

By Pauline Anderson
The Medical Post, February 20, 1996

TORONTO - The significant number of depressed patients who don't respond adequately to selected serotonin reuptake inhibitors (SSRls) could benefit from the addition of a tricyclic antidepressant (TCA), an open trial at the Clarke Institute of Psychiatry here has confirmed.

Treatment-resistant depression according to psychiatry resident Dr. Roger McIntyre, is "a very common problem."

Even newer generation antidepressants have only about a 70% efficacy rate, a figure which includes partial and full responders, he told delegates at the Ontario Psychiatric Association (OPA) meeting.

Although treatment resistance in depression is a difficult term to define, most definitions "allude to the criterion of adequacy of dose and duration of the (drug) trial" noted Dr. Emmanuel Persad, professor of psychiatry at the University of Western Ontario and a psychiatrist at the London Psychiatric Hospital.

But pharmacotherapy may not be the sole factor related to this drug resistance. Comorbidity may also contribute to treatment resistance in depressed patients, said Dr. Persad.

Whatever the reason, there are patients whose symptoms don't improve with antidepressants. The question of what to do with them has interested the medical profession for years.

In the past, said Dr. Mclntyre, doctors often would substitute one tricyclic antidepressant with another, with "little research to say that was a useful strategy." Or they would augment antidepressants with other drugs such as stimulants.

Increasing evidence

But increasingly, there's evidence to show that combination strategies using TCAs with SSRIs may provide the best results.

In the current study researchers at the Clarke's mood disorder clinic took 16 patients -- six men and 10 women with a mean age of 33 -- diagnosed with major depression (Hamilton score greater than 16) who had been treated with fluoxetine (Prozac, 20-80 mg per day) for at least five weeks.

Patients were augmented with the drug desipramine at a dose of one mg per kg of body weight. Depression scores and blood levels of the tricylic were taken after one, two and three weeks.

Nine patients responded to the drug augmentation at week three with response being defined as a reduction in the Hamilton depression score of 50% or a total score of less than 12. The mean scores went down in these patients from 18.22 to 6.14.

Mean desipramine plasma levels for responders was significantly higher than for non-responders at week three (910 nmol/L compared to 518 nmol/L), suggesting the response may be a dose-related phenomenon, according to Dr. McIntyre.

Dr. Persad noted that adding a tricyclic in many cases alleviates such symptoms as sleep disruption and anxiety in depressed patients.

The Clarke researchers concluded that augmenting fluoxetine with a tricyclic "may be an effective protocol in fluoxetine non-responders," said Dr. McIntyre.

Asked how he could be sure that the non-responders to fluoxetine wouldn't have responded simply by increasing the dose of that drug, Dr. Mclntyre said that since they hadn't responded by the start of the study, it would be very unlikely they would have responded later.

He said controlled trials are now needed to confirm these results.

Copyright 1996 Maclean Hunter Publishing Limited
Reprinted with permission.

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