Furious Seasons

September 24, 2007

More Evidence That Anti-Depressants Are Bad For Bipolar Disorder

As I noted in March, the recently-completed STEP-BD study found that anti-depressants were virtually useless in treating bipolar depression. In fact, a placebo beat the meds. Now, comes another paper from STEP-BD showing that anti-depressants are ineffectual for depression in bipolar disorder.

This time out, researchers measured the effect of using anti-depressants in patients with co-occurring manic and depressive episodes, or mixed states. Results:

"In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy."

No surprise there. An editorial in the same issue of the American Journal of Psychiatry noted:

"[T]his article adds to the growing evidence that in the setting of adequate therapeutic mood stabilizer prescription, the addition of antidepressants appears to provide little additional benefit for depressed bipolar patients but may impart a risk of switching to mania."

So why is it that doctors continue to prescribe anti-depressants for bipolar disorder? Don't they read research articles? Anti-depressants have been handed out like candy to bipolars since the late-1980s and now it makes you wonder just how much of this was the result of possible off-label marketing of the drugs--which remain unapproved for use in bipolar disorder--especially in light of the damage they've caused bipolars. I have to count myself as one of those unlucky many.

I remember going to my psych doc several times in the mid-1990s, complaining of increased rather than lessened depression while on Lithium and a host of anti-depressants, and also complaining about a feeling of agitation on the meds. He assured me each time that research showed that anti-depressants worked for bipolar disorder--and so each time I accepted his decision to either dramatically up my dose of Prozac or switch to Paxil or Zoloft. And, then, came the awful suicidality which I contended with for well over a year. Fun times.

So what are doctors to do when faced with a patient with bipolar disorder with strong depressive symptoms? A subject for another day.

Posted by Philip Dawdy at September 24, 2007 12:03 AM

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Comments

Don't they read research articles?

No.

(Although to be fair, there is a lot to keep track of. CME is one of the only ways to get through to them, I think.)

Posted by: techne at September 24, 2007 08:21 AM

One antidepressant in particular has worked reasonably consistently for myself over the last 25 years. Of course this kicked me into hypo/mania at times but the pdocs have put me on a mood stabilizer the last ten years and haven't had a manic episode since.

We're all individual and need to use what works.

Posted by: abba at September 24, 2007 01:15 PM

As long as there is no improvement in the availability of drugs that work for bipolar depression I see another reason for noncompliance with medication. I've been diagnosed with Bipolar type I for 15 yrs with a predominance of depressive symptoms. Yes, the diagnosis was finally made with a notablemixed episode that landed me in the psych unit for 3 wks in 1992 but in spite of several mixed episodes,one resulting in a brief hospitalization most of my life has been spent in a depressed state that makes hypomania look attractive. My psychiatrist isn't really interested at this point as long as I'm not manic. Well Depakote and Lithium don't make it as far as I'm concerned so I'd like to see some research efforts get kicked into high gear.

Posted by: Lisa Lindemann at September 26, 2007 07:30 PM

"So what are doctors to do when faced with a patient with bipolar disorder with strong depressive symptoms?"

Short answer:

Nourish the brain, for starters. It is not the
answer to all brain problems, but it creates a
context in which healing is much more likely.
Omega-3 fats, magnesium, taurine, zinc, niacin,
tryptophan or 5-HTP, lithium in physiologic
amounts, etc., etc. Also ascorbic acid to
modulate dopamine functions. THEN,
having created a context (a relatively-healthy,
well-nourished brain), add SMALL, graded
doses of SSRIs/SNRIs, or TCAs, as needed to achieve
the desired effect without manic breakthroughs
(the likelihood of the latter being greatly
reduced by nutritional therapy). In some
cases the drugs will not be needed at all.

Posted by: Alan at October 6, 2007 09:44 AM

I forgot to mention thyroid. Thyroid has
been around forever as a potentiator of
antidepressant meds, and hypothyroidism is a
vast (and underappreciated) problem. This
can be the limiting factor in many cases.
Further, a rather striking item linking
thyroiditis with bipolar was just published;
see abstract below.

Guy Abraham claims that autoimmune
thyroiditis is caused by iodine deficiency;
see links below. Thyroiditis has sometimes
been said to be *caused* by excessive iodine
exposure; however, this may have been the
result of insufficiency of ascorbic acid
and/or magnesium. See the Abraham writeups
linked below for full details.

Thyroid hormone replacement is usually part
of the treatment of autoimmune thyroiditis.

----------------------

"[A]utoimmune thyroiditis is related not
only to bipolar disorder itself but also to
the genetic vulnerability to develop the
disorder."

----------------------

http://www.sciencedirect.com

Biological Psychiatry

Volume 62, Issue 2, 15 July 2007, Pages
135-140

Bipolar Disorder: Neurocircuitry &
Neurodevelopment

doi:10.1016/j.biopsych.2006.08.041

Original Article

Is Autoimmune Thyroiditis Part of the
Genetic Vulnerability (or an Endophenotype)
for Bipolar Disorder?

Ronald Vonka, , , Astrid C. van der Schotb,
Ren‚ S. Kahnb, Willem A. Nolenc and Hemmo A.
Drexhaged

aReinier van Arkel group, 's-Hertogenbosch,
The Netherlands

bDepartment of Psychiatry, University
Medical Centre Utrecht, Utrecht, The
Netherlands

cUniversity Medical Center Groningen,
Groningen, The Netherlands

dDepartment of Immunology, Erasmus Medical
Centre Rotterdam, The Netherlands.

Received 8 June 2006; revised 24 August
2006; accepted 25 August 2006. Available
online 4 December 2006.

Background

Both genetic and environmental factors are
involved in the etiology of bipolar
disorder; however, biological markers for
the transmission of the bipolar genotype
("endophenotypes") have not been found.
Autoimmune thyroiditis with raised levels of
thyroperoxidase antibodies (TPO-Abs) is
related to bipolar disorder and may be such
an endophenotype. This study was intended to
examine whether autoimmune thyroiditis is
related to the disease itself, to the
(genetic) vulnerability to develop bipolar
disorder, or both.

Method

Blood was collected from 22 monozygotic (MZ)
and 29 dizygotic (DZ) bipolar twins and 35
healthy matched control twins to determine
TPO-Abs.

Results

The TPO-Abs were positive in 27% of the
bipolar index twins, 29% of the monozygotic
bipolar cotwins, 27% of the monozygotic
nonbipolar cotwins, 25% of the dizygotic
bipolar cotwins, 17% of the dizygotic
nonbipolar cotwins, and in 16% of the
control twins. Repeated measures analysis of
covariance on log-transformed absolute
TPO-Abs values revealed significantly
increased mean TPO-Abs levels in discordant
twin pairs as compared with healthy twin
pairs, whereas no difference was found
between bipolar patients and their
(discordant) nonbipolar cotwins.

Conclusions

This study shows that autoimmune thyroiditis
is related not only to bipolar disorder
itself but also to the genetic vulnerability
to develop the disorder. Autoimmune
thyroiditis, with TPO-Abs as marker, is a
possible endophenotype for bipolar disorder.

Key Words: Bipolar disorder; endophenotype;
genetic risk; immunology; thyroid
autoimmunity; twins

Address reprint requests to R. Vonk, M.D.,
Reinier van Arkel groep, P.O. Box 70058,
5201 DZ, 's-Hertogenbosch, The Netherlands

------------------------------------------------------------------

ABRAHAM, IODINE:

http://findarticles.com/p/articles/mi_m0FDL/is_1_13/ai_n17212623/print
FindArticles > Original Internist > Spring, 2006
The history of iodine in medicine Part I: from
discovery to essentiality

http://findarticles.com/p/articles/mi_m0FDL/is_2_13/ai_n17213860/print
FindArticles > Original Internist > June, 2006
The history of iodine in medicine Part II: the
search for and the discovery of thyroid hormones

http://findarticles.com/p/articles/mi_m0FDL/is_2_13/ai_n17213861/print
FindArticles > Original Internist > June, 2006
The history of iodine in medicine Part III:
thyroid fixation and medical iodophobia

Posted by: Alan at October 6, 2007 10:07 AM