They describe a large sample (400) of patients from Sardinia, Italy, who had responded well to antidepressants, and then stopped taking them. The antidepressants had been prescribed for either depression, or panic attacks.People who quit suddenly (over 1-7 days) were more likely to relapse, and relapsed sooner, than the ones who stopped gradually (over a period of 2 weeks or more).
This graph shows what % of the patients in each group remained well at each time point (in terms of days since their final pill.) As you can see, the two lines separate early, and then remain apart by about the same distance (20%) for the whole 12 months.What this means is that rapid discontinuation didn't just accelerate relapses that were "going to happen anyway". It actually caused more relapses - about 1 in 5 "extra" people. These "extra" relapses all happened in the first 3 months, because after that, the slope of the lines is identical.
On the other hand, they rarely happened immediately - it's not as if people relapsed within days of their last pill. The pattern was broadly similar for older antidepressants (tricyclics) and newer ones (SSRIs).
The authors note that these data throw up important questions about "relapse prevention" trials comparing people who stay on antidepressants vs. those who are switched - abruptly - to placebo. People who stay on the drug usually do better, but is this because the drug works, or because the people on placebo were withdrawn too fast?
This was an observational study, not an experiment. There was no randomization. People quit antidepressants for various "personal or clinical reasons"; 80% of the time it was their own decision, and only 20% of the time was it due to their doctor's advice.
So it's possible that there was some underlying difference between the two groups, that could explain the differences. Regression analysis revealed that the results weren't due to differences in dose, duration of treatment, diagnosis, age etc., but you can't measure every possible confound.
Only randomized controlled trials could provide a final answer, but there's little chance of anyone doing one. Drug companies are unlikely to fund a study about how to stop using their products. So we have only observational data to go on. These data fit in with previous studies showing that there's a similar story when it comes to quitting lithium and antipsychotics. Gradual is better.
But that's common sense. Tapering medications slowly is a good idea in general, because it gives your system more time to adapt. Of course, sometimes there are overriding medical reasons to quit quickly, but apart from in such cases, I'd always want to come off anything as gradually as possible.
Baldessarini RJ, Tondo L, Ghiani C, & Lepri B (2010). Illness risk following rapid versus gradual discontinuation of antidepressants. The American journal of psychiatry, 167 (8), 934-41 PMID: 20478876
12 comments:
I echo your final words, but would add that doctors (particularly GPs) and mental health nurses are unaware of the severity of symptoms that some people experience when coming off these particular medications. Given that the symptoms can often mimic the disorder being treated, it is all to easy to suggest restarting drug therapy, when in actual fact a more considered approach to tapering individuals off these medications (e.g. cross tapering to a medication with a longer half life) may be what is required.
Paul (RNMH)
I would love to see a study of this type with a placebo arm!
See, I see something completely different in that chart. Within 1 year even with slow tapering almost 60% of people relapse. I have to question the wisdom of stopping the medications at all.
I agree with Anonymous #2. Recurrent depression is by definition a highly recurrent disorder. Based on early work of Jules Angst and the Pittsburgh group (Ellen Frank and David Kupfer) I used to teach that the risk of recurrence is 50% within 6months after stopping imipramine. That is pretty much what you see in the Figure in this post by NS. Continuation treatment with the antidepressant drug does prevent or delay recurrences. It also is more efficacious than manual directed interpersonal psychotherapy. In fact, the NNT (Number Needed to Treat) to prevent a recurrence with 1 year of continuation imipramine treatment is astonishingly small - it is about 3. That seems to be the case even for the SSRI drugs, whereas their NNT for obtaining remission of an ongoing episode is much weaker at around 10.
Jules Angst opined, based on his data, that suitable candidates for maintenance antidepressant drug treatment should have experienced at least 3 lifetime episodes of depression, two in the past 5 years.
Well, it's notable that in 80% of cases, the patient made the decision to quit, rather than their clinicians.
So yes, maybe they should have stayed on it.
However, I think this adds to the body of evidence saying that if you are going to quit, you should do it slowly.
Dr. Carroll:
Debate is healthy, but try to keep it real, OK?
J Consult Clin Psychol. Author manuscript; available in PMC 2009 June 1.
Published in final edited form as:
J Consult Clin Psychol. 2008 June; 76(3): 468–477.
doi: 10.1037/0022-006X.76.3.468.
PMCID: PMC2648513
NIHMSID: NIHMS90181
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Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression
Keith S. Dobson, Steven D. Hollon, Sona Dimidjian, Karen B. Schmaling, Robert J. Kohlenberg, Robert Gallop, Shireen L. Rizvi, Jackie K. Gollan, David L. Dunner, and Neil S. Jacobson
Keith S. Dobson, University of Calgary;
Contributor Information.
Correspondence concerning this article should be addressed to: Keith S. Dobson, University of Calgary, Calgary, Alberta, Canada T2N 1N4, Email: ksdobson@ucalgary.ca Pre-publication manuscript. Please do not cite without permission (12/12/07)
The publisher's final edited version of this article is available at J Consult Clin Psychol
See other articles in PMC that cite the published article.
Abstract
This study followed treatment responders from a randomized controlled trial of adults with major depression. Patients treated with medication but withdrawn onto pill-placebo had more relapse through one year of follow-up, compared to patients who received prior behavioral activation, prior cognitive therapy, or continued medication. Prior psychotherapy was also superior to medication withdrawal in the prevention of recurrence across the second year of follow-up. Specific comparisons indicated that patients previously exposed to cognitive therapy were significantly less likely to relapse following treatment termination than patients withdrawn from medication, and patients previously exposed to behavioral activation did almost as well relative to medication withdrawal at the level of a nonsignificant trend. Differences between behavioral activation and cognitive therapy were small in magnitude and not significantly different across the full two-year follow-up, and each was at least as efficacious as continuation medication. These findings suggest that behavioral activation may be nearly as enduring as cognitive therapy, and that both psychotherapies are less expensive and longer-lasting alternatives to medication in the treatment of depression.
Keywords: Behavioral Activation, Cognitive Therapy, Antidepressant
@ Anonymous today: Thanks for your comment. I think we are not really in disagreement. As usual, the devil is in the details when it comes to comparing reports in the literature. The report by Dobson that you highlighted addressed the effect of prior psychotherapy on the durability of antidepressant drug response following discontinuation. The Pittsburgh reports to which I referred studied a different question, namely, the effect of introducing interpersonal psychotherapy following drug discontinuation.
Most likely the two reports also differed in respect of patient characteristics. The patients studied by Ellen Frank and David Kupfer had an established history of recurrences. Do you know if that was the case in the Dobson report?
As both a biologist and a psych patient, this conclusion feels very obvious. A gradual tapering has long been used when changing meds.
As for whether it's a good idea to stop the medication at all, it's important to remember that psych medications can be prohibitively expensive and have very strong side effects. Through in a social stigma against psych medication, and there exist many patient-driven reasons to get off meds.
In my experience, psychiatrists wouldn't tell a patient to stop medication that was helping him, but frequently deal with patients that want to get off medication for outside reasons, and need to come up with the safest way for them to do so. Unlike researchers, they can't simply tell their patients that it's a stupid idea, because it turns the patient off to care completely, which is dangerous.
I don't understand why they don't take a holistic approach to psychi like they do in medicine.
It seems so wrapped up in confidentiality that an all inclusive therapy alongside meds are just not bothered with.
I have yet to meet a single person who found their therapy sessions beneficial to long term stability.
When you confide in a friend, not all friends know what they're doing, or helping you at all.
Are shrinks really any different aside from the professional tone, Aristotelian detachment and the stash they can prescribe you with?
Maybe the problem is the heavy use of meds to 'cure' diagnoses when it could be just laziness on the shrink’s part, or lack of alternative support options due to confidentiality.
Anon above- Not sure if I totally understood you, but I think there have been a lot of studies that people with all manner of illness who have intimacy and support tend to heal faster and better. I haven't seen one of these specifically for mental health, but I believe it's likely to have a similar affect.
There was recently a study about how talk therapy can assist people who feel lonely. I couldn't help but wonder... is it that they "reframed their thoughts" that made them feel less lonely, or is it the fact that they were getting to talk to a human being about their feelings at all that made them feel less lonely?
"What this means is that rapid discontinuation didn't just accelerate relapses that were "going to happen anyway". It actually caused more relapses - about 1 in 5 "extra" people."
I have to disagree with this. The decline clearly still hasn't tapered off by the end of the study; we don't know that the number of relapses after two years (or more) wouldn't have been the same.
Fair point. If you extrapolate the lines as linear, they meet at about 2 years.
If you assume they continue to flatten, it's longer.
The difference between the lines (20%) builds up over the first 3 months or so, and then stays pretty much constant.
So yes, they might end up meeting. But they might not. We need a longer study.
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