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Academic papers on SSRI efficacy

protovack

protovack

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Hi all, long time member but havne't posted in ages due to med school.

Well, I'm in family medicine residency now and I have my own patients that I inherited from outgoing graduates, many of whom are on SSRIs.

I am fairly skeptical of their efficacy and I need papers in my pocket I can pull out when my superiors quiz me about why I want to take people off SSRIs or not put them on them in the first place.

Preferably randomized controlled trials comparing SSRIs to things like placebo, counseling, family therapy, diet/lifestyle modifaction, etc.

I just don't have the time to do an in depth literature review.

thanks!
 
Are you looking only for studies that refute the efficacy of SSRI's, or studies on efficacy with any results? Because believe it or not it's harder these days to find a study showing 0 improvement with SSRI's. Here's a recent one looking at citalopram (no big pharma funding): Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study.

Here's some results from the STAR*D trials (huge multilayer analysis of various AD drugs): Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

I think those results are really interesting. They show that when the first AD drug fails, the next one to three drugs trialed will almost always allow the patient to achieve remission, but when the first drug fails the patient is more likely to relapse at long term follow up regardless of the efficacy of the 2nd-4th drug. So with that in mind I could see why you would take a patient off an SSRI that wasn't working, but would you really take a patient in remission off their meds?
 
They are better then placebo but only by 3% or so, take in mine placebo is noise that wears off over time, so while the difference may be minimal, long term if may be a lot bigger.

That said I allways recommened mdai or other sero releasers as more effective alternatives but only for those that are willing to take unresearched chemicals, amt is an example that has been researched tough wich also releases da.
 
MeDieViL said:
They are better then placebo but only by 3% or so, take in mine placebo is noise that wears off over time, so while the difference may be minimal, long term if may be a lot bigger.
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You can't just pull a number out of thin air like that. Does that apply to every SSRI - they're all 3% or so better than placebo? That applies to every indication SSRIs are used for?

MeDieViL said:
That said I allways recommened mdai or other sero releasers as more effective alternatives but only for those that are willing to take unresearched chemicals, amt is an example that has been researched tough wich also releases da.
Click to expand...

I think it's generally assumed that serotonin releasers are totally non-sustainable in the long term. Just look at the loss of effectiveness of MDMA used two days in a row to see why. Maybe that's just because people tend to dose too high, I really don't know, it just doesn't sound reasonable for an indication that requires a daily treatment. Has your experience been different?


Back to the OP's question I realized you didn't specify an indication, and SSRI's are used for a lot more than MDD obviously, so I pulled a few meta-reviews for you:

For OCD (pediatric) SSRI's come out behind CBT: Differential efficacy of cognitive-behavioral therapy and pharmacological treatments for pediatric obsessive-compulsive disorder: a meta-analysis.
For post partum depression SSRI's come out well ahead of placebo, but not significantly better than other pharmacotherapies or psychological intervention: Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials.
Back to MDD, SSRI's tend to be better than TCA's when compared directly: Selective Serotonin Reuptake Inhibitors Versus Tricyclic Antidepressants in Young Patients: A Meta-analysis of Efficacy and Acceptability.

Those are just a handful of the reviews published this year alone. It's almost mind boggling how much gets published on these drugs. From the small sample I've been able to read myself SSRI's pretty much always come out ahead of placebo for the traditional indications (MDD, OCD, anxiety disorders), but they usually come out about equal to psychological counseling and other pharmacotherapies. Better than nothing, but not necessarily better than anything else, I guess.
 
Ive used MDAI in daily low therapeutic doses for a longer period and it definatly was sustainable, abusing mdma wich also has dopaminergic effects and that with taking recreational not therapeutic doses doesn't mean anything.

Ill post some reviews generally placebo was like 30% remission (placebo completely disappears after a few months) while ssris around 33% and that number wont disappear, placebo is not sustainable so even drugs that aren't better then placebo can actually be effective.
 
The most recent meta-analysis that I've encountered is this: http://jama.jamanetwork.com/article.aspx?articleid=185157 It concludes that there is little or no benefit of antidepressants over placebo in patients with mild or moderate depression, but it's substantial in those with severe depression.

Conclusions of an earlier meta-analysis were more radical: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2253608/ It stirred a lot of controversy when it was published.

But even with those results, if an SSRI works for someone and doesn't produce adverse effects, why would you take them off it? Even if it's mostly a placebo effect, it's still an improvement in their lives. While I think antidepressants are overprescribed, let's not take it too far in the other direction.
 
Placebo effects go away after a few months, while the efficacy in studys in similar, placebo is just noise, long term efficacy proves that its not placebo, just that placebo temporary improves as many people.
 
MeDieViL said:
Placebo effects go away after a few months, while the efficacy in studys in similar, placebo is just noise, long term efficacy proves that its not placebo, just that placebo temporary improves as many people.
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Evidence for that? At least one study doesn't support your statement: http://www.ncbi.nlm.nih.gov/pubmed/18036616

Besides, what do you mean calling placebo "noise"? Placebo effect is a real phenomenon and can be quite powerful.
 
Mandark said:
Evidence for that? At least one study doesn't support your statement: http://www.ncbi.nlm.nih.gov/pubmed/18036616

Besides, what do you mean calling placebo "noise"? Placebo effect is a real phenomenon and can be quite powerful.
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I think that study actually supports his claim that the placebo effect is less robust over time than the antidepressant effect, albeit only to a small degree. They compared people 6-8 weeks after starting either AD or placebo, then took only those people from those groups that achieved remission, then asked whether they were still in remission between 16-52 weeks later. Since the placebo group had 79% still in remission while AD group had 93% the AD treatment was more persistent for 14% of people.

They also mention that the AD group had a higher % of people achieving remission at the 6-8 week time point. So based on that data the AD was more efficacious than placebo at 6-8 weeks, and that difference was even greater at later time points.
 
endotropic said:
I think that study actually supports his claim that the placebo effect is less robust over time than the antidepressant effect, albeit only to a small degree.
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Yes, it's less robust, but it's still pretty robust, as the authors themselves emphasize (rather strongly: The widely held belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking.). It certainly doesn't "go away".

I have no access to full article, but it seems that the paper unfortunately doesn't look at possible differences in response and its persistance depending on initial severity of depressive symptoms.
 
SSRIs have been shown to be slightly less effective than placebo. You might as well be prescribing vitamins, unless flat affect and sexual dysfunction are considered desirable for some reason.
 
Dresden said:
SSRIs have been shown to be slightly less effective than placebo. You might as well be prescribing vitamins, unless flat affect and sexual dysfunction are considered desirable for some reason.
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That very well may be, but when you say something "has been shown" you should be prepared to support it with something, especially when even the most critical studies linked already show modest positive benefits from SSRI treatment. Otherwise you're just spreading propaganda/hearsay instead of informing the debate.


Mandark said:
Yes, it's less robust, but it's still pretty robust, as the authors themselves emphasize (rather strongly: The widely held belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking.). It certainly doesn't "go away".

I have no access to full article, but it seems that the paper unfortunately doesn't look at possible differences in response and its persistance depending on initial severity of depressive symptoms.
Click to expand...

The studies they reviewed balanced each group so that initial severity was equal between the two treatment conditions.

I tend to just look at the available data and make my own conclusions instead of reading the authors interpretation. Introduction/discussion sections are just more he said she said as far as I'm concerned, show me what actually happened.
 
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Sorry, but I am not smart enough to remember all the citations for all the drug studies I've ever read.
 
Mandark said:
Yes, it's less robust, but it's still pretty robust, as the authors themselves emphasize (rather strongly: The widely held belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking.). It certainly doesn't "go away".

I have no access to full article, but it seems that the paper unfortunately doesn't look at possible differences in response and its persistance depending on initial severity of depressive symptoms.
Click to expand...
Yes but that's for a period of a year, what about after 2 years? antidepressants can work for decades.
 
1.1 Depression[edit source | editbeta]

Antidepressants are recommended by the National Institute for Clinical Excellence (NICE) as a first-line treatment of severe depression and for the treatment of mild-to-moderate depression that persists after conservative measures such as cognitive therapy.[7] They recommend against their routine use in those who have chronic health problems and mild depression.[7]
There has been controversy regarding the efficacy of antidepressants in treating depression depending on its severity and duration.

  • Two meta-analyses published in 2008 (Kirsch) and 2010 (Fournier) found that in mild and moderate depression, the effect of SSRIs is small or none compared to placebo, while in very severe depression the effect of SSRIs is between "relatively small " and "substantial".[3][8] The 2008 meta-analysis combined 35 clinical trials submitted to the U.S. Food and Drug Administration (FDA) before licensing of four newer antidepressants (including the SSRIs paroxetine and fluoxetine, the non-SSRI antidepressant nefazodone, and the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine. The authors attributed the relationship between severity and efficacy to a reduction of the placebo effect in severely depressed patients, rather than an increase in the effect of the medication.[8] Some researchers have questioned the statistical basis of this study suggesting that it underestimates the effect size of antidepressants.[9][10]
  • A 2010 comprehensive review conducted by NICE concluded that antidepressants have no advantage over placebo in the treatment of short term mild depression, but that the available evidence supported the use of antidepressants in the treatment of dysthymia and other forms of chronic mild depression.[11]
  • A 2012 meta-analysis of the SSRIs fluoxetine and venlafaxine concluded that statistically and clinically significant treatment effects were observed for each drug relative to placebo irrespective of baseline depression severity.[12]
There does not appear to be a big difference in the effectiveness among the second generation antidepressants (SSRIs and SNRIs).[13]
In children there is concerns around the quality of the evidence on the meaningfulness of benefits seen.[14] If a medication is used, fluoxetine appears to be first line.[14]



That would be wikipedia's content, though I edited some of the formatting.
Ref 13 is a meta-analytic review from 2011
Ref 14 is a Cochrane Collaboration meta-analytic systematic review

That's 6 meta-analyses/reviews/systematic-reviews (in other words probably ~100+ randomized controlled trials) right there. ;)
 
endotropic said:
The studies they reviewed balanced each group so that initial severity was equal between the two treatment conditions.
Click to expand...
What I meant is: it would be interesting to know whether the persistance of placebo effect would be different in patients with mild to moderate depression versus severe depression, akin to the difference in efficacy found in meta-analyses from my previous post.

MeDieViL said:
Yes but that's for a period of a year, what about after 2 years? antidepressants can work for decades.
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Why do you assume that placebo can't?
 
Mandark said:
What I meant is: it would be interesting to know whether the persistance of placebo effect would be different in patients with mild to moderate depression versus severe depression, akin to the difference in efficacy found in meta-analyses from my previous post.


Why do you assume that placebo can't?
Click to expand...

Because that paper proofs the placebo effect slowly tapers off, why would it suddenly stop after the study duration?
 
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