Furious Seasons

November 18, 2008

Medical Group Releases Anti-Depressant Guidelines, Admits Little Differences Between Drugs

The American College of Physicians, the big internal medicine group, yesterday released its clinical practice guidelines for the treatment of depression with anti-depressants. Non-psychiatrists prescribe about 80 percent of anti-depressants and most of those would be written by internists and GPs and family medicine docs, so these guidelines are important in that presumably a high percentage of the docs who prescribe anti-depressants might actually read them.

They are important in another regard: the guidelines assert that there is virtually no difference in efficacy among second generation anti-depressants (SSRIs, SNRIs, etc.), so in other words the differences among anti-depressants are pretty much like the differences between brands of gasoline; and, the guidelines assert that there is solid evidence for suicidality in some people taking anti-depressants, something that come as a shock to members of the American Psychiatric Association.

First, I do want to point out what I consider some omissions in the guidelines. One, while I know the title is "Using Second-Generation Anti-Depressants to Treat Depressive Disorders," there is no recommendation for psychotherapy or CBT, which is odd considering that Britain's NICE has determined that there is plenty of evidence to make CBT a first line treatment (after diet, exercise and watchful waiting). The ACP guidelines do state that the psychotherapies are effective, but leave it at that (then again, what do you expect from MDs?). But it is 2008 now, not 1993.

There is also no discussion whatsoever in the guidelines of withdrawal or how to get patients off of anti-depressants. That's an interesting omission considering that the ACP guidelines do not call for lifetime treatment of depression with anti-depressants. More on that in a bit.

As to anti-depressant efficacy, the guidelines state:

"The results of individual studies showed no significant differences between SSRIs or between SSRIs and SNRIs, SSNRIs, or other second-generation antidepressants. Some evidence from meta-analyses showed statistically significant differences between treatments; however, the effect sizes were small and the results were probably not clinically significant."

After two decades of companies trying to carve out comparative advantages for their anti-depressants, that's a stunning bit of news.

"Studies evaluating the risk for suicidality (suicidal thinking or behavior) in patients showed no differences among second-generation antidepressants (90–94). However, 1 meta-analysis showed that although no evidence indicated an increase in the risk for suicide with SSRIs (odds ratio, 0.85 [CI, 0.20 to 3.40]), the risk for nonfatal suicide attempts did increase (odds ratio, 1.57 [CI, 0.99 to 2.55]) (91). Another meta-analysis of published data (95) showed similar results, with SSRIs associated with an increased risk for suicide attempts compared with placebo (odds ratio, 2.25 [CI, 3.3 to 4.6])."

So there you have it: a fairly learned group of doctors has determined that, based upon the scientific evidence available to them, anti-depressants can cause suicidality. Someone ought to alert the producer of "The Infinite Mind" radio show, after this year's show where several docs claimed there is no evidence for suicidality.

Feel free to review the guidelines yourself and see what they say about other problems associated with anti-depressant use. I'm sure some readers, who I know truly hate anti-depressants, will find their assessments incomplete, but it's fairly honest document, as these sorts of things go.

As far as how long doctors should treat a patient with anti-depressants, the guidelines state:

"Patients who achieve remission with acute-phase treatment should continue receiving antidepressant therapy for 4 to 9 months to prevent relapse. No evidence indicates differences among second-generation antidepressants in preventing relapse (loss of response during continuation-phase treatment) or recurrence (loss of response during maintenance-phase treatment). Patients who have had 2 or more episodes may benefit from a longer duration of therapy (years to lifelong)."

While I appreciate that the guidelines do leave open the possibility of lifetime treatment with anti-depressants, it's clear to me that this isn't the emphasis. That's a huge change from generally-accepted principles circa-1995. It's not perfect, but it's sure better.

What puzzles me, however, is that since the ACP guidelines admit that patients will want to go off anti-depressants and that that would be clinically desirable, there is no discussion or advice whatsoever relating to how to get patients off anti-depressants.

I wonder why.

Posted by Philip Dawdy at November 18, 2008 12:03 AM

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Comments

The other thing that's omitted is a discussion of rebound. Let's not assume that the "relapse" they speak of here is really anything other than another drug-induced or withdrawal-induced reaction (because of dosage tolerance and thus lost "efficacy"). Many clinical trials (like STAR*D for instance) have actually demonstrated that the longer you stay on antidepressants and the more different ones you try, the smaller your chances of lasting remission really are. This smacks of rebound to me. Depression will actually get worse and there's less chance of healing the longer you are on antidepressants and the more different ones you try. And this is precisely because of chemical dependency and the withdrawal issues that will come back to bite you in some way or other even if you stay on "for life" - the withdrawal that is being ignored by the medical profession. This failure to evaluate long term outcomes of people who take antidepressants vs. those who don't is a serious omission in the study of these treatments. If outcomes were seriously looked at, the withdrawal issue couldn't be ignored.

Posted by: Sara at November 18, 2008 08:02 AM

Maybe if these researchers didn't have ties to the drug makers, they would have said these drugs do in fact cause people to kill themselves. It is getting harder and harder for pharma to deny this. But they still manage to do so. And as long as they continue to do so many more lives will be lost and many more lives will be turned upside down with these medications. When will Psychiatrist understand that while depression is a bitch, they make it much worse with the medications?

Posted by: Jane at November 18, 2008 08:59 AM

I don't see anything new.

There are 100 References and two of them:

21. Nemeroff CB, Thase ME, EPIC 014 Study Group. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. J Psychiatr Res. 2007;41:351-9. [PMID: 16165158].[Medline]

25. Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ, Comparative Efficacy Antidepressants Study Group. Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs. 2005;19:137-46. [PMID: 15697327].[Medline]

Mr. Versiani, he's Brazilian, and his colleagues have just came up with this finding:

Do SSRIs or antidepressants in general increase suicidality? WPA Section on Pharmacopsychiatry: consensus statement.
Möller HJ, Baldwin DS, Goodwin G, Kasper S, Okasha A, Stein DJ, Tandon R, Versiani M; WPA Section on Pharmacopsychiatry.
Collaborators (42)

Department of Psychiatry, Ludwig-Maximilians-University München, Nussbaumstrasse 7, 80336 Munich, Germany. hans-juergen.moeller@med.uni-muenchen.de

In the past few years several papers have reported critically on the risk of suicidal thoughts and behaviour associated with antidepressants, primarily SSRIs. The risk-benefit ratio of antidepressant (AD) treatment has been questioned especially in children and adolescents. The critical publications led to warnings being issued by regulatory authorities such as the FDA, MHRA and EMEA and stimulated new research activity in this field. However, potential harmful effects of antidepressants on suicidality are difficult to investigate in empirical studies because these have several methodological limitations. Randomised controlled trials (RCTs) are the most reliable way to test the hypothesis that AD have such side effects. In addition to meta-analyses of RCTs, complementary research methods should be applied to obtain the most comprehensive information. We undertook a comprehensive review of publications related to the topics ADs, suicide, suicidality, suicidal behaviour and aggression. Based on this comprehensive review we conclude that ADs, including SSRIs, carry a small risk of inducing suicidal thoughts and suicide attempts, in age groups below 25 years, the risk reducing further at the age of about 30-40 years. This risk has to be balanced against the well-known beneficial effects of ADs on depressive and other symptoms (anxiety, panic, obsessive-compulsive symptoms), including suicidality and suicidal behaviour. According to the principles of good clinical practice, decision making should consider carefully the beneficial effects of AD treatment as well as potentially harmful effects and attempt to keep the potential risks of AD treatment to a minimum. It is the major problem facing efforts to identify the possible 'suicidal effects' of antidepressants.
http://www.ncbi.nlm.nih.gov/pubmed/18668279?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

All I see is are more and more reviews, studies, clinical trials and all underestimating side effects.
The risks are potential nothing we should care about.
I believe that even if all people who are taking ADs committed suicide they would say:

"Oops! These suicides might be related to ADs. However we still need more evidences."

Posted by: Ana at November 18, 2008 09:02 AM

Yes, there is little difference among the SSRIs and SNRIs. While studying www.SSRIstories.com, I realized that all the SSRIs & SNRIs, without exception, cause suicides, murders and mayhem. They are all equal in this regard.

Since we know that "homicidal ideation" is listed as an adverse reaction in the insert to Effexor and that the Zoloft study in children showed "homicidal ideation" as a Frequent side effect, then we can assume all of the SSRIs & SNRIs cause "homicidal ideation".

A mother who had an 18 year old daughter on Prozac kill her boyfriend and herself in front of a tanning salon on Coit Road in Dallas, Texas in the mid-1990's said: "I can accept the fact that my daughter committed suicide even though this is killing me, but I can never accept the fact that she murdered someone".

So all these SSRIs & SNRIs equally cause pain and suffering to the survivors of these murders, suicides and murder-suicides.

Posted by: Rosie at November 18, 2008 10:47 AM

the study has a lot of points worth discussing. main pt being: no acknowledgement that psychotherapy has superior efficay than 40% metioned for ssris with none of these nasty "adverse events."

but here is another curious point:
their conflict of interest statement. now keep in mind: Ann Int Med is supported by pharma advertising. Ann Int Med supported the research. Lead author has been supported by Endo, who is working to get SSRIs approvd for tx of pain - yes, pain is mentioned in this ssri article.

The authors note the ONLY COI is for Author Snow. And then they declare that ANY possible conflicts have been considered and "resolved." Resolved? What does that mean?

Posted by: MedsVsTherapy at November 19, 2008 09:14 AM