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A recent study from the national mental health institute shows that antidepressants are not effective in the treatment of BP.

Mood stabilizers alone were effective..

IM on epival and effexor


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Hi Vinton,

What study are you referring too? Is there a link you can provide us to check it out? Thanks



it was posted in the new England jounal of medicine and the whole story is in French that I got from a similar site as ours.If you want it I can give it.

I got a short resume below.

My article includes a full study with 2 groups
Previous Volume 357:614-616 August 9, 2007 Number 6

Adjunctive Antidepressant Treatment for Bipolar Depression

Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

Related Article by Belmaker, R.H.

Related Article by Sachs, G. S.

To the Editor: Sachs et al. (April 26 issue)1 report that adding an adjunctive antidepressant drug offers no benefit over continued mood-stabilizer monotherapy in the treatment of bipolar depression. This finding contradicts some previous studies and the experience of many clinicians. In his thoughtful accompanying editorial, Belmaker2 identifies possible reasons for this discrepancy, including diagnostic heterogeneity and changes in the manifestation of bipolar disorder during the past 20 years. These observations are perhaps too circumspect.

The past two decades have seen a marked increase in the diagnosis of bipolar disorder by North American psychiatrists.3 This trend has many origins: a . . .
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Would you provide us with the URL links to your articles?

Is the article you are reading a French translation of an article published in the New Engalnd Joural of Medicine?

Is this the NEJM reference?

Volume 357:614-616 August 9, 2007 Number 6
Adjunctive Antidepressant Treatment for Bipolar Depression

We'll try to get more details on the article if you can point us in the right direction.


Here is the French version I got from the pychomedia site which is similar to ours.Maybe someone can get it from NEJM or Eurkealert

D?pression bipolaire, antid?presseur inutile avec stabilisateur de l'humeur
PsychoM?dia - Publi? le 29 mars 2007

Une recherche am?ricaine financ?e par le National Institute of Mental Health (NIMH) montre que pour les gens souffrant d'un ?pisode de d?pression du trouble bipolaire et qui prennent un stabilisateur de l'humeur, l'ajout d'un antid?presseur n'est pas plus efficace qu'un placebo (une pilule de sucre).

Le trouble bipolaire, caract?ris? par une alternance

d'?pisodes de manie et de d?pression, est habituellement trait? avec des stabilisateurs de l'humeur tels que le lithium, l'?pivale (valproate), le Tegretol (carbamaz?pine) et d'autres qui r?duisent la manie.

Les ?pisodes de d?pression sont toutefois plus courants que les ?pisodes de manie et ont tendance ? ?tre plus longs. Le traitement de la d?pression bipolaire est particuli?rement difficile, selon Thomas R. Insel, directeur du NIMH.

Des antid?presseurs sont souvent utilis?s en combinaison avec un stabilisateur de l'humeur pour traiter les ?pisodes de d?pression mais ils sont consid?r?s comme associ?s ? un risque accru de passage ? un ?pisode de manie.

Gary Sachs et des coll?gues ont suivi 366 personnes souffrant de trouble bipolaire. Contrairement ? la plupart des ?tudes cliniques, les participants ?taient recrut?s dans les services de sant? et inclus m?me s'ils souffraient d'autres troubles tels que l'abus de substance, l'anxi?t? ou de sympt?mes psychotiques, ce qui rend les r?sultats plus g?n?ralisables aux situations de la vie r?elle. Les antid?presseurs utilis?s dans cette recherche ?taient le Wellbutrin (bupropion) et le Paxil (paroxetine).

Apr?s 26 semaines de traitement, 24% des participants ayant re?u un antid?presseur et 27% de ceux ayant re?u un placebo sont demeur?s en r?mission au moins 8 semaines. L'antid?presseur n'?tait donc pas plus efficace que le placebo.

De plus, environ 10% dans chaque groupe, avec antid?presseur et avec placebo, ont vu appara?tre des sympt?mes de manie, ce qui remet en question la croyance selon laquelle les antid?presseurs peuvent provoquer le d?clenchement un ?pisode maniaque.

Les r?sultats ont ?t? similaires avec les deux antid?presseurs.

Les r?sultats montrent, selon Dr. Sachs, qu'ajuster le dosage du stabilisateur de l'humeur peut ?tre une strat?gie plus valable que d'ajouter un antid?presseur dans le traitement des ?pisodes d?pressifs du trouble bipolaire.

Ces r?sultats sont surprenants, commente un ?ditorial en ligne du New England Journal of Medicine, car des ?tudes europ?ennes avaient montr? une efficacit? des antid?presseurs pour le trouble bipolaire. Des ?tudes suppl?mentaires sont n?cessaires pour v?rifier si certains antid?presseurs seraient plus efficaces que d'autres. Les auteurs croient aussi que des ?tudes ? plus long terme seraient n?cessaires car leur recherche est ? relativement court terme.

Une prochaine ?tape du projet de recherche sera de v?rifier l'efficacit? des traitements de psychoth?rapie.

Source: New England Journal of Medicine, 2007, March 28 (Eurekalert)

Voyez ?galement:


Source: NEJM

Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression


Background Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania.

Methods In this double-blind, placebo-controlled study, we randomly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo, under conditions generalizable to routine clinical care. A standardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, was used at all follow-up visits. The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery (8 consecutive weeks of euthymia). Secondary effectiveness outcomes and rates of treatment-emergent affective switch (a switch to mania or hypomania early in the course of treatment) were also examined.

Results Forty-two of the 179 subjects (23.5%) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery, as did 51 of the 187 subjects (27.3%) receiving a mood stabilizer plus a matching placebo (P=0.40). Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes. Rates of treatment-emergent affective switch were similar in the two groups.

Conclusions The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch. Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder.

Gary S. Sachs, M.D., Andrew A. Nierenberg, M.D., Joseph R. Calabrese, M.D., Lauren B. Marangell, M.D., Stephen R. Wisniewski, Ph.D., Laszlo Gyulai, M.D., Edward S. Friedman, M.D., Charles L. Bowden, M.D., Mark D. Fossey, M.D., Michael J. Ostacher, M.D., M.P.H., Terence A. Ketter, M.D., Jayendra Patel, M.D., Peter Hauser, M.D., Daniel Rapport, M.D., James M. Martinez, M.D., Michael H. Allen, M.D., David J. Miklowitz, Ph.D., Michael W. Otto, Ph.D., Ellen B. Dennehy, Ph.D., and Michael E. Thase, M.D.

Daniel E.
One of the letters to the editor:

To the Editor: The trial by Sachs and colleagues is the latest in a string of studies showing that the addition of antidepressants to mood stabilizers in depressed bipolar patients is of minimal benefit.(1,2) However, antidepressants given in the absence of a mood stabilizer — either alone (in type II illness) (3,4) or added to a second-generation antipsychotic drug (5) — are effective in treating bipolar depression. The major difference in the design of these studies is the absence or presence of mood stabilizers. When mood stabilizers (lithium or valproate, carbamazepine, or lamotrigine) are used, antidepressants are of minimal benefit. This finding has traditionally been interpreted as showing that mood stabilizers have an intrinsic antidepressant effect, which cannot be augmented by the antidepressant agent. An alternative interpretation that would reconcile the discrepant data is that mood stabilizers may actually interfere with or block the effect of antidepressant drugs. This distinction is important, since it would alter the approach to treating depression in patients with bipolar disorder. Studies that specifically examine this question need to be performed.

Rif S. El-Mallakh, M.D.
University of Louisville School of Medicine


1. Nemeroff CB, Evans DL, Gyulai L, et al. Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry 2001;158:906-912. [Free Full Text]
2. Post RM, Leverich GS, Nolen WA, et al. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord 2003;5:396-406. [CrossRef][ISI][Medline]
3. Amsterdam J. Efficacy and safety of venlafaxine in treatment of bipolar II major depressive episode. J Clin Psychopharmacol 1998;18:414-417. [CrossRef][ISI][Medline]
4. Amsterdam JD, Garcia-España F, Fawcett J, et al. Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol 1998;18:435-440. [CrossRef][ISI][Medline]
5. Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003;60:1079-1088.

The authors' response to the letters to the editor:

The authors reply: Price and Tyrka comment on several trends related to the diagnosis of bipolar disorder, which raise concerns we share. However, as we detailed in our article, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) rigorously applied DSM-IV criteria both in the selection of subjects at initial entry into the program and for inclusion in the randomized study of acute depression. We do not believe our results necessarily contradict those of previous studies. Instead, we suggest that our conclusions differ from those of previous studies largely because in our study, durable recovery was the primary outcome variable. As we stated, the results of our cross-sectional, last-observation-carried-forward analyses, as typically applied in most previous studies of short-term treatment, revealed a proportion of subjects treated with antidepressants who had rates of successful outcome similar to those reported in previous studies. However, mood stabilizers alone provided an equivalent benefit in the depressed subjects with bipolar disorder whom we studied.

Dr. Henry and colleagues raise the issue of heterogeneity and suggest a differential response on the basis of two principal subtypes of depression in bipolar disorder: global inhibition and activation. Although their proposed typology is potentially interesting, the existence of such heterogeneity is unlikely to account for the absence of difference between study groups in our randomized study. Notably, no increase in suicidality was observed in subjects treated without standard antidepressants. STEP-BD does plan to examine symptom profiles obtained at baseline as predictors of treatment outcome.

Dr. El-Mallakh makes a scientific point that cannot be adequately resolved currently. Treating acute bipolar depression for short periods with antidepressants alone could result in higher response rates than the use of antidepressants in combination with mood stabilizers. However, a blinded maintenance study (1) reported lower response rates when patients with bipolar disorder who were receiving placebo under double-blind conditions became depressed and received adjunctive antidepressants, as compared with the response rates observed when the antidepressants were added to mood stabilizers in a blinded fashion. To our knowledge, no published study has had design features that directly address Dr. El-Mallakh's supposition, which requires that patients be randomly assigned to receive antidepressants in combination with a mood stabilizer or as monotherapy. Since evidence-based treatment guidelines consistently recommend the concurrent use of a mood stabilizer, it is likely that ethical concerns, as well as concerns about practical complexities and study costs, account for the lack of such initiatives.

Dr. Belmaker's concern about limited generalizability and low recruitment rates in our study requires some clarification. Unlike most clinical trials, STEP-BD enrolled a large number of patients with bipolar disorder who were seeking treatment. However, the relatively low percentage of depressed patients who underwent randomization reflected the large number of patients who were ineligible owing to previous treatment with both bupropion and paroxetine, an unwillingness to accept treatment with approved mood stabilizers, or an unwillingness to taper the dose of a current antidepressant medication. However, we acknowledge that results from our study may not apply to all antidepressants, since our study examined only bupropion and paroxetine.
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