Wednesday, March 25, 2009

Long-term antidepressant therapy to prevent relapse

Maintenance antidepressant therapy is likely to reduce the probability of depressive relapse. This would involve continuing to take an antidepressant, long-term, even when feeling better. I would restrict such a recommendation to those who have had recurrent or severe depressions. Such maintenance therapy is best indicated for those who have actually had an acute benefit from a specific antidepressant.

I emphasize the importance of psychotherapy and healthy lifestyle change, which also reduce relapse rates (in the case of CBT, for example, the reduction in relapse rate persists long after the course of CBT is over).

This is a 2008 link to findings from the so-called PREVENT study, which showed that 67% of patients on venlafaxine remained well over 2.5 years of follow-up, compared to 41% of patients on placebo:

A weakness of this study is that they did not allow for an extremely gradual taper of venlafaxine in the group randomized to receive placebo maintenance; therefore the worse outcome in the placebo maintenance group could have partly been due to withdrawal symptoms. However, there is a brief discussion of this possibility in some letters from the Journal of Clinical Psychiatry (2008 May; 69(5): 865-866) , and the authors of the PREVENT study make some good points about why withdrawal symptoms are not likely to account for the worse outcome in the placebo group.

There are a variety of older studies showing reduced relapse rates in patients taking long-term antidepressant maintenance. Here is an example, using imipramine:

Withdrawal effects are unlikely to account for the worse outcome in the control group, because the control group actually still received the active antidepressant, but just at a lower dose. The point of this study is that a full dose of the antidepressant is probably required in a long-term maintenance phase.

Here is another study from 1992 in Archives of General Psychiatry, showing significant preventative effects from taking full-dose imipramine over 5 years of follow-up, with or without adjunctive psychotherapy:

Here is a link to a 1990 study in Archives of General Psychiatry showing that full-dose imipramine had substantial preventative effects, moreso than interpersonal therapy, over 3 years of follow-up:

For this study, I need to go back and look carefully over the full text, which I can't find at this moment.

This study is another compelling piece of evidence, from JAMA in 1999, supporting antidepressant maintenance, and it had an excellent design:

It showed that elderly patients who had recovered from a bout of recurrent depression, who then received placebo, had a relapse rate of 90% over 3 years. Treatment with interpersonal psychotherapy alone reduced the relapse rate to 64% over 3 years. Treatment with the antidepressant nortriptyline alone reduced this relapse rate to 43% over 3 years. Nortriptyline plus interpersonal therapy combined, led to a relapse rate of only 20% over 3 years. Withdrawal effects from notriptyline are unlikely to have substantially favoured the nortriptyline group, since the follow-up was over a 3 year period, which is way beyond any period of withdrawal effects.

Here is another 2007 review paper, from The Canadian Journal of Psychiatry, summarizing strong research support that long-term antidepressant therapy reduces relapse rate in major depression by about 50%:


purplesque said...

Interesting post. As a psychiatry resident I've been taught than anybody with more than two episodes of (unprovoked) major depression needs to be on anti-depressant maintenance therapy. I wonder what you make of that.

GK said...

I think that maintenance therapy is needed following any episode of depression.

Some types of "maintenance therapy" could start BEFORE any episode of depression has even started (e.g. I think ideas about CBT, managing emotions, healthy lifestyle, etc. should be taught to children as a form of primary prevention).

If episodes of depression have been recurrent or severe, then the need for maintenance therapy is higher and more urgent.

"Maintenance therapy" could mean lifestyle change, psychotherapy (short-term or long-term), or medications.

I think the decision about what type of maintenance therapy is best has to be negotiated together, between physician and patient, in a trusting, ongoing therapeutic relationship, following a discussion about the benefits and risks of the different options.