A Polypharmacy Approach

You underwent a major depression and the doctor treated you with antidepressants. You waited the six weeks, and you still were ill. Perhaps not as depressed as you were originally, but still bothered with insomnia, feeling sad and/or anxious and having little appetite. You tried another medication and felt the same. Now there’s a new term to label you: treatment resistant/ refractory depression (TRD).

Some doctors would next try a polypharmacy approach to eliminate the depression. This is as long as a person has been given a proper diagnosis such as unipolar vs. bipolar and has been on a significant dosage of the deemed correct medications for a long enough time period. Sometimes side effects may interfere with this dosage amount.

There are four approaches to treatment refractory depression:

1) Optimization-Maximizing the dose/serum level/time. Prescribing antidepressant medication in dosages that are too low and for lengths of time that are too short are common causes of treatment failure.

2) Substitution-Substituting one antidepressant for another within the same or different family (one selective serotonin re-uptake inhibitor (SSRI) for another one, for example). In some control groups, the latter has shown to have a better response rate.

3) Augmentation-Adding a medicine, such as lithium, that is not routinely regarded as an antidepressant when there is only a partial response to the primary antidepressant agent.

4) Combination-Using two primary antidepressants together. This therapy involves the addition of a second antidepressant agent to the regimen. Concurrent administration of two or more antidepressant agents (e.g., adding trazodone [Desyrel], desipramine [Norpramine] or bupropion [Wellbutrin] to fluoxetine) may yield a different response than that produced by use of either drug alone.

Doctors will have their different approaches depending on the patient’s particular circumstances, as well as their experiences with other patients’ treatment.

Below are just a few examples of these combinations. If you suffer from TRD, this will give you a start on your possible next step in treatment.

Dr. Scott Aaronson, M.D., psychiatrist in private practice, Newton Centre, MA. Supplements anti-depressants with the new atypical psychotics, such as Zyprexa and Seraquel. He reports a lot of success with supplementing anti-depressants with these new anti-psychotics, and gives the example of a depressed patient whose suicidal ideation was not relieved until she was placed on Zypreza, in spite of the prior use of several different anti-depressants.

A 21-year-old woman who suffered from severe depression and talked of suicide was given a combination of venlafaxine (Effexor) and bupropion (wellbutrin). She responded positively to the treatment

Underdosing is a frequent cause of treatment failure, so ensuring that adequate doses get an adequate trial is imperative. Increasing dosages of tricyclic (TCA) antidepressants even beyond recommended ranges may be considered when response to a 6-week trial at the high end of the recommended range is less than optimal; though there is little data supporting this tactic with SSRIs.

The significant number of depressed patients who don’t respond adequately to selected (SSRls) could benefit from the addition of a (TCA), an open trial at the Clarke Institute of Psychiatry confirmed. The patients had been treated with fluoxetine (prozac) for at least five weeks; their medication was augmented with the drug desipramine.