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Munkholm, 2019 Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis


Linus

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BMJ Open 2019;9:e024886

 

Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

 

Klaus Munkholm, Asger Sand Paludan-Müller, Kim Boesen (Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark

 

Source: BMJ Open

 

Full text is available here : https://bmjopen.bmj.com/content/9/6/e024886

 

Objectives : To investigate whether the conclusion of a recent systematic review and network meta-analysis (Cipriani et al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.

 

Conclusions : The evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

 

Our results highlight that the many hundreds of placebo-controlled trials of antidepressants have not addressed the most important, patient-relevant questions regarding antidepressants’ benefits and harms. Although this has been known for years,13 it has not led to changes in research practice. Erroneous conclusions that antidepressants are efficacious for depression have the effect that they may prevent people suffering from depression from seeking other solutions to alleviate their condition, such as psychotherapy and dealing with psychosocial stressors, and they may stall funding and research of such treatment modalities. Importantly, such conclusions may also lead to a loss of interest in providing a better evidence base to determine the true clinical value of antidepressants.

 

Our review has two implications. First, the review by Cipriani et al 5 and its conclusion should be carefully revisited. In the light of our findings, the review should not inform clinical practice. Second, our reanalysis has highlighted the need for a radical change in the way antidepressant trials are being conducted, reported and interpreted. We hope that doctors, patients, peers and politicians will consider the limitations of the current evidence of antidepressants for depression that we have presented and collectively act accordingly. This involves informing the patients about the limitations of the current evidence, thus providing a basis for a true informed consent, and working towards a better evidence base for the use of antidepressants in the treatment of depression. To get reliable answers about the antidepressants’ benefits and harms in adults with depression, we need large-scale, industry-independent and better blinded, long-term trials of drug naïve participants, with patient-relevant outcomes rather than ranking scales.

Escitalopram 1.05 mg (max of 30 mg, taper from 10 mg to now started september 2016)

 

Klonopin 0.3 mg (one dosage reduction of 25 percent, from 0.4 to 0.3 mg september 2017)

 

Supplements: magnesium malate, fish oil, curcumin, multivitamin, iodine, probiotics, vitamine D along with eating healthy 80 percent of the time, I have no problem whatsoever taking supplements.

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Researcher Michael P. Hengartner PhD (follow him on twitter, he is great) about this reanalysis :

 

"So I think that it‘s quite safe to conclude that the bias-corrected difference between drug and placebo in RCT is significantly smaller than 2 HAMD points, presumably very close to 0."

 

So basically what this means is that antidepressants are no more effetive than sugar pills with potentially serious side effects and  the possibility you will suffer horrible withdrawal when you come off them.

Escitalopram 1.05 mg (max of 30 mg, taper from 10 mg to now started september 2016)

 

Klonopin 0.3 mg (one dosage reduction of 25 percent, from 0.4 to 0.3 mg september 2017)

 

Supplements: magnesium malate, fish oil, curcumin, multivitamin, iodine, probiotics, vitamine D along with eating healthy 80 percent of the time, I have no problem whatsoever taking supplements.

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Let's see how pharma spins/blocks this one.

"Nothing so small as a moment is insurmountable, and moments are all that we have. You have survived every trial and tribulation that life has thrown at you up until this very instant. When future troubles come—and they will come—a version of you will be born into that moment that can conquer them, too." - Kevin Koenig 

 

I am not a doctor and this should not be considered medical advice. You can use the information and recommendations provided in whatever way you want and all decisions on your treatment are yours. 

 

In the next few weeks I do not have a lot of capacity to respond to questions. If you need a quick answer pls tag or ask other moderators who may want to be tagged. 

 

Aug  2000 - July 2003 (ct, 4-6 wk wd) , citalopram 20 mg,  xanax prn, wellbutrin for a few months, trazodone prn 

Dec 2004 - July 2018 citalopram 20 mg, xanax prn (rarely used)

Aug 2018 - citalopram 40 mg (self titrated up)

September 2018 - January 2019 tapered citalopram - 40/30/20/10/5 no issues until a week after reaching 0

Feb 2019 0.25 xanax - 0.5/day (3 weeks) over to klonopin 0.25 once a day to manage severe wd

March 6, reinstated citalopram 2.5 mg (liquid), klonopin 0.25 mg for sleep 2-3 times a week

Apr 1st citalopram 2.0 mg (liquid), klonopin 0.25 once a week (off by 4/14/19- no tapering)

citalopram (liquid) 4/14/19 -1.8 mg, 5/8/19 - 1.6 mg,  7/27/19 -1.5 mg,  8/15/19 - 1.35, 2/21/21 - 1.1 (smaller drops in between), 6/20/21 - 1.03 mg, 8/7/21- 1.025, 8/11/21 - 1.02, 8/15/21 - 1.015, 9/3/21 - 0.925 (fingers crossed!), 10/8/21 - 0.9, 10/18/21 - 0.875, 12/31/21 - 0.85, 1/7/22 - 0.825, 1/14/22 - 0.8, 1/22/22 - 0.785, 8/18/22 - 0.59, 12/15/2022 - 0.48, 2/15/22 - 0.43, 25/07/23 - 0.25 (mistake), 6/08/23 - 0.33mg

 

Supplements: magnesium citrate and bi-glycinate

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On 7/10/2019 at 11:41 AM, Onmyway said:

Let's see how pharma spins/blocks this one. 

 

Maybe they won't even bother to reply... This also goes for all psychiatrists who, when the Cipriani meta-analysis came out, claimed the debate was settled: "antidepressants do work" (even though it only showed a two point improvement on the Hamilton depression scale in comparison with placebo, which may be statistically significant, but in my book is not clinically significant). Now with this re-analysis we know the difference is much smaller, probably zero, but I would not hold my breath in waiting for a reply by "establishement" psychiatrists.

 

Good luck with your taper, you can do this !

Escitalopram 1.05 mg (max of 30 mg, taper from 10 mg to now started september 2016)

 

Klonopin 0.3 mg (one dosage reduction of 25 percent, from 0.4 to 0.3 mg september 2017)

 

Supplements: magnesium malate, fish oil, curcumin, multivitamin, iodine, probiotics, vitamine D along with eating healthy 80 percent of the time, I have no problem whatsoever taking supplements.

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  • 2 weeks later...

Ok, there is a reply by two psychiatrists from Switzerland (not aware of any others). Researcher Michael Hengarnter replies.

 

 

 

They simply claimed that the drugs may have been found not to work better than placebo in scientific studies, but that in practice they do. The meta-analysis, again according to these two psychiatrists, is not relevant for everyday practice. They also claim that switching to another drug or changing the dosage would have been proven in practice. Scientific studies tell another story.

 

Evidence-based medicine trown out of the window. It works because we say it works. Brilliant !

 

One more thing: both psychiatrists have financial conflicts of interest and in the past have accepted payments from the pharmaceutical industry.

 

 

 

 

Escitalopram 1.05 mg (max of 30 mg, taper from 10 mg to now started september 2016)

 

Klonopin 0.3 mg (one dosage reduction of 25 percent, from 0.4 to 0.3 mg september 2017)

 

Supplements: magnesium malate, fish oil, curcumin, multivitamin, iodine, probiotics, vitamine D along with eating healthy 80 percent of the time, I have no problem whatsoever taking supplements.

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On 7/22/2019 at 12:11 PM, Linus said:

Ok, there is a reply by two psychiatrists from Switzerland (not aware of any others). Researcher Michael Hengarnter replies.

 

 

 

They simply claimed that the drugs may have been found not to work better than placebo in scientific studies, but that in practice they do. The meta-analysis, again according to these two psychiatrists, is not relevant for everyday practice. They also claim that switching to another drug or changing the dosage would have been proven in practice. Scientific studies tell another story.

 

Evidence-based medicine trown out of the window. It works because we say it works. Brilliant !

 

One more thing: both psychiatrists have financial conflicts of interest and in the past have accepted payments from the pharmaceutical industry.

 

 

 

 

Wow! I don't know if I should feel sorry for them (and the m-r-ns who published it) because they doesn't understand statistics or be furious because they don't understand statistics and then publish opinions that could damage the lives of millions of people or furious because they understand all that and still write and publish things like that for their industry puppets. I choose furious. 

 

You ----ing evil 'authors',  they "work" because

 

1) they work as a placebo. Unfortunately, these drugs also have negative short and long-term side effects including dementia and so so many others in addition to withdrawal. These placebos literally ruin lives and leave others on pause for years. 

 

2) you ----ing ---ots ignore the experience of those for whom they don't work in the clinic and put them on the merry-go

-round of polydrugging and  withdrawing and switching among multiple meds with horrific consequences 

 

3) your pals at pharma help you close your eyes in 2). It's easy to ignore human suffering when these consulting fees pay for the new pool in your backyard and the private school education of your kids and the yoga classes of your spouse. The hell with the suffering of your patients! 

 

How is it that it is only in psychiatry that science and evidence become the enemy or somehow insufficient for clinical practice? Psychiatric patients are less than human?

 

 

"Nothing so small as a moment is insurmountable, and moments are all that we have. You have survived every trial and tribulation that life has thrown at you up until this very instant. When future troubles come—and they will come—a version of you will be born into that moment that can conquer them, too." - Kevin Koenig 

 

I am not a doctor and this should not be considered medical advice. You can use the information and recommendations provided in whatever way you want and all decisions on your treatment are yours. 

 

In the next few weeks I do not have a lot of capacity to respond to questions. If you need a quick answer pls tag or ask other moderators who may want to be tagged. 

 

Aug  2000 - July 2003 (ct, 4-6 wk wd) , citalopram 20 mg,  xanax prn, wellbutrin for a few months, trazodone prn 

Dec 2004 - July 2018 citalopram 20 mg, xanax prn (rarely used)

Aug 2018 - citalopram 40 mg (self titrated up)

September 2018 - January 2019 tapered citalopram - 40/30/20/10/5 no issues until a week after reaching 0

Feb 2019 0.25 xanax - 0.5/day (3 weeks) over to klonopin 0.25 once a day to manage severe wd

March 6, reinstated citalopram 2.5 mg (liquid), klonopin 0.25 mg for sleep 2-3 times a week

Apr 1st citalopram 2.0 mg (liquid), klonopin 0.25 once a week (off by 4/14/19- no tapering)

citalopram (liquid) 4/14/19 -1.8 mg, 5/8/19 - 1.6 mg,  7/27/19 -1.5 mg,  8/15/19 - 1.35, 2/21/21 - 1.1 (smaller drops in between), 6/20/21 - 1.03 mg, 8/7/21- 1.025, 8/11/21 - 1.02, 8/15/21 - 1.015, 9/3/21 - 0.925 (fingers crossed!), 10/8/21 - 0.9, 10/18/21 - 0.875, 12/31/21 - 0.85, 1/7/22 - 0.825, 1/14/22 - 0.8, 1/22/22 - 0.785, 8/18/22 - 0.59, 12/15/2022 - 0.48, 2/15/22 - 0.43, 25/07/23 - 0.25 (mistake), 6/08/23 - 0.33mg

 

Supplements: magnesium citrate and bi-glycinate

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On 7/22/2019 at 12:11 PM, Linus said:

They simply claimed that the drugs may have been found not to work better than placebo in scientific studies, but that in practice they do. The meta-analysis, again according to these two psychiatrists, is not relevant for everyday practice. They also claim that switching to another drug or changing the dosage would have been proven in practice. Scientific studies tell another story.

 

Post-truth psychiatry: "Our (sponsored) belief is as good as your scientific evidence".

 

😖

1999 - 2001: Paroxetine 20mg, 2003: Venlafaxine 75mg, 2003 - 2014: Escitalopram 20mg

1999 - December 2017: Lansoprazole 15mg

2014 - December 2017: Citalopram 20mg

December 2017: Mirtazapine 30mg, stopped after 4 days due to immediate bad reaction, Zopiclone 3.75mg, stopped after 2 days due to immediate bad reaction

January 2018 - April 2018: Citalopram liquid, tapering, final dose 0.1mg

December 2018 onwards: Vitamin C 1000mg

October 2021: Loratadine 10mg for 6 days (23/10 to 28/10)

Long term (for asthma): Salbutamol and Salmeterol inhalers, Salmeterol stopped March 2021 due to migraine headaches

Occasional use for headaches: Paracetamol 40mg or Ibuprofen 40mg

4th December 2021: Eustachian tube infection: Amoxicillin 500mg 3 per day for 5 days, Dexamethasone & Neomycin ear spray 3 per day for 1 week, Beclometasone nasal spray 2 per day for 2 weeks.

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4 hours ago, AlanC said:

 

Post-truth psychiatry: "Our (sponsored) belief is as good as your scientific evidence".

 

😖

Brilliant! This should be the motto of the American Psychiatric Association! And its British equivalent... 

"Nothing so small as a moment is insurmountable, and moments are all that we have. You have survived every trial and tribulation that life has thrown at you up until this very instant. When future troubles come—and they will come—a version of you will be born into that moment that can conquer them, too." - Kevin Koenig 

 

I am not a doctor and this should not be considered medical advice. You can use the information and recommendations provided in whatever way you want and all decisions on your treatment are yours. 

 

In the next few weeks I do not have a lot of capacity to respond to questions. If you need a quick answer pls tag or ask other moderators who may want to be tagged. 

 

Aug  2000 - July 2003 (ct, 4-6 wk wd) , citalopram 20 mg,  xanax prn, wellbutrin for a few months, trazodone prn 

Dec 2004 - July 2018 citalopram 20 mg, xanax prn (rarely used)

Aug 2018 - citalopram 40 mg (self titrated up)

September 2018 - January 2019 tapered citalopram - 40/30/20/10/5 no issues until a week after reaching 0

Feb 2019 0.25 xanax - 0.5/day (3 weeks) over to klonopin 0.25 once a day to manage severe wd

March 6, reinstated citalopram 2.5 mg (liquid), klonopin 0.25 mg for sleep 2-3 times a week

Apr 1st citalopram 2.0 mg (liquid), klonopin 0.25 once a week (off by 4/14/19- no tapering)

citalopram (liquid) 4/14/19 -1.8 mg, 5/8/19 - 1.6 mg,  7/27/19 -1.5 mg,  8/15/19 - 1.35, 2/21/21 - 1.1 (smaller drops in between), 6/20/21 - 1.03 mg, 8/7/21- 1.025, 8/11/21 - 1.02, 8/15/21 - 1.015, 9/3/21 - 0.925 (fingers crossed!), 10/8/21 - 0.9, 10/18/21 - 0.875, 12/31/21 - 0.85, 1/7/22 - 0.825, 1/14/22 - 0.8, 1/22/22 - 0.785, 8/18/22 - 0.59, 12/15/2022 - 0.48, 2/15/22 - 0.43, 25/07/23 - 0.25 (mistake), 6/08/23 - 0.33mg

 

Supplements: magnesium citrate and bi-glycinate

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