My blog has moved!

You should be automatically redirected in 6 seconds. If not, visit
and update your bookmarks.

Tuesday, February 26, 2008

New Antidepressants only better than Placebo in Severe Depression

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients.

This is the conclusion of a meta-analysis of all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. These antidepressants are: include fluoxetine, venlafaxine, nefazodone, paroxetine. The article is published in PloS Medicine and free to read. They specifically tested the influence of depression severity and outcome of these newer antidepressants compared to placebo.

The overall result of the meta-analysis comparing these new antidepressants with placebo confirmed earlier analyzes. Weighted mean improvement was 9.60 points on the HRSD in the drug groups and 7.80 in the placebo groups, yielding a mean drug–placebo difference of 1.80 on HRSD improvement scores. Although the difference between these means easily attained statistical significance it does not meet the three-point drug–placebo criterion for clinical significance used by NICE.

They also found that efficacy reaches clinical significance only in trials involving the most extremely depressed patients, and that this pattern is due to a decrease in the response to placebo rather than an increase in the response to medication.

Now I am not a great fan of these newer antidepressants especially with severe depression. In the past Anderson and others have shown a couple of times in reviews and randomized controlled trials that TCA are significantly better for depressed inpatients.
These inpatients with depression are more likely to be suicidal, psychotically depressed (30%) and suffer from psychiatric and somatic co morbidity. In the review by Anderson the Tricyclic Antidepressants were used in a low average dosage and mostly not plasma controlled. Patients can benefit from plasma level controlled dosing of tricyclic antidepressants. Therapeutic dosage is reached faster, and side-effects due to a high dosage is prevented.

This outcome of this meta-analysis seems to bold to be true, might be the selection of trials?
Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J., Johnson, B.T. (2008). Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine, 5(2), e45. DOI: 10.1371/journal.pmed.0050045
Anderson, I. (2000). Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. Journal of Affective Disorders, 58(1), 19-36. DOI: 10.1016/S0165-0327(99)00092-0
Broek, W., BirkenhĂŻ¿½ger, T., Mulder, P., Bruijn, J., Moleman, P. (2004). A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients. Psychopharmacology DOI: 10.1007/s00213-004-1853-3
Bruijn, J.A., Moleman, P., Mulder, P.G., van den Broek, W.W., van Hulst, A.M., van der Mast, R.C., van de Wetering, B.J. (1996). A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients. Psychopharmacology, 127(3), 231-237. DOI: 10.1007/s002130050081


Aqua said...

An article about this was in the paper this morning and my anti-antideppresant/medication husband latched onto it as proof his stance is right. He believes and is very vocal (read: pushy and domineering) about the medications being the reason I am not getting better.

Please, please, please, if you can provide us with more information about why this analysis may be flawed, and/or more simple information/ or proof that tricyclic or MAOI's should not be lumped in with this study

I am a patient, so I find it difficult to understand a lot of the technical jargon and I would like to show some positive information to my husband.

I know this sounds like a huge question, but anything big or small would be appreciated.

Dr. Shock said...

I could bother you with a lot more bla bla, but be assured that after treating many depressed patients for years, I am convinced that there is really a place for antidepressants.
It all comes down to understand your patient, having a working relationship, patience, good diagnostic skills and proper drug treatment. With the latter I mean clearly explain benefits, side-effects (most patients don't even use their medication due to unwanted effects), proper dosing and good evaluation and monitoring.
Had a post about it I think yesterday.
Regards Dr Shock.

Dr. Shock said...

Here is another sensible post about this article:

steve hayes said...

As the director of Novus Medical Detox, I often see patients who are on alcohol or opioids, central nervous system depressants, also taking antidepressants. When they detox they find they don't need the antidepressants.

This is good news because a Swedish study showed that 52% of the 2006 suicides by women on antidepressants. Since antidepressants work no better than placebos and are less effective than exercise in dealing with depression.

There is a prescription drug epidemic and these are leaders in the list of terribe abuses.

Steve Hayes