AD Controversy 4: continue or taper? (more)

(continued from the main Antidepressant Controversies page):

From here, we’re digging into those studies. If you’re up to it, or skeptical of my conclusion, read on (more….).

The “Altshuler” study

(lead author, among many: Lori Altshuler)

Among psychiatrists who know something about the research on this question, this is the study they have probably heard of. Yet despite how frequently it is cited, the Altshuler report was not a randomized trial; i.e. not a fair comparison between patients who were kept on their antidepressant versus those who were deliberately taken off. (It may appear so from the graph unless one looks closely). Many patients were screened out before arriving at the final results, far more than were followed through the reporting period.

The bottom line: in this study, patients to stay on antidepressants did substantially better than patients who — for whatever reason — were taken off their antidepressants. Yet because the patients were not randomly assigned to one or the other approach, we don’t know if taking the antidepressant out is what caused them to do less well. They might have done less well because something else was going wrong, and that was the basis for coming off the antidepressant. What we really need is a true randomized trial; and that is what we have, albeit quite small, in the second study below.

If you are really interested in the details, you might wish to see a breakdown of the structure and results of the Altshuler study. It is amazing how often this study is cited, and how firmly, given the way it is structured (a naturalistic follow-up of a select group of patients).

The STEP-BD study

(Lead author, among many: Nassir Ghaemi)

Data from this study have already been described in detail under Controversy 3, More. The conclusion: for patients with a history of rapid cycling, coming off the antidepressant leads to a better outcome. For those who did not have rapid cycling, the data are equivocal; staying on might be just slightly better, but coming off does not leave people clearly worse. If you have already worked your way through the Ghaemi paper description above, you will recognize the graph below, which supports these conclusions.

contro2 (1)

The dark line is the mood course of those who stopped their antidepressants. This graph shows just depression scores. You can see a quick but short-term worsening in the first 4 months but after that they’re about the same as the (dotted line) patients whose antidepressants were continued. True, everyone’s depresssion scores are up compared to where they started. But the stoppers aren’t any worse than the continuers!

My opinion, as regards this last controversy: just about every patient with bipolar disorder needs a trial off of antidepressants (with the antidepressant very slowly tapered, to get
there). A few patients clearly do better when they are maintained on an antidepressant, almost always in conjunction with a mood stabilizer medication. These patients are a distinct minority, perhaps 10% at best in my practice (about 20% in some bipolar specialty clinics Ghaemi).

The “new” Altshuler study

This team of investigators includes some of the most widely respected authors in psychiatry. I don’t mean to dismiss their work. At the same time, there is still complete agreement in psychiatry that randomized trials are a better guide than naturalistic studies (the former both an experimental group and a placebo or control group; the latter are based on observations of a group as a whole). So it’s important to look carefully at this study because although it is billed as a randomized trial, it is effectively closer to a naturalistic

This team of authors put together the comparison trial in which the switch-potential of antidepressants, for patients on mood stabilizers, was compared. That studyLeverich has been described briefly in Controversy 2. After that trial was completed, participants were given the opportunity to continue the treatment to which they had been randomly assigned. That’s why the authors call this new report a “randomized trial”, but the randomization was not to continuing or stopping antidepressants. It was simply a continuation study, and that is basically very like the first “Altshuler” study described above in this section.

The results: of those who did very well when they first got on an antidepressant in addition to their mood stabilizer (“acute positive response”), 70% continued to do well up to 1 year. The others: 13% relapsed into depression, and 17% had a manic episode (not thought to be related to the antidepressant; the authors note that this “switch” rate is similar to that for patients on mood stabilizers alone. Recall that this trial did not have a placebo group for a direct switch rate comparison).

By comparison, of those who had only a partial improvement when they first got on the antidepressant in addition to their mood stabilizer (“acute partial response”), 6 out of 22 (27%) ended up with a more positive response later.

Bottom line here: that’s useful and does help reassure that staying on one’s antidepressant, if it works well, is probably okay for up to a year. Beyond that we don’t know. The trial does not comment on whether it’s better overall to stay on an antidepressant long term or not. The STEP-BD trial (#2 just above in this section) is a direct examination of that question, and the conclusion there was clear: if you have rapid cycling bipolar disorder, you’re better off tapering off antidepressants. If not rapid cycling, then the choice is broader.