Article: "This is why a third of antidepressants are prescribed for something else"

[Andy]

Doctors often use medicines ‘off-label’ to treat people with conditions that these drugs haven’t been tested on. Leah Shaffer explores how uncovering the secret life of antidepressants in particular could open up a host of new treatments.

19 December 2017

It was when he became a father that Michael Briggs resolved to somehow bring his ulcerative colitis under control. He was determined to avoid what many people with the disease end up needing – having part or all of their large intestine removed. A trained scientist, manager of a physics lab at the University of New Hampshire, he began reading medical research papers, looking for anything that might help him.

He knew there wouldn’t be just one single cure, just as he knew there was not one single cause behind this inflammatory bowel disease (IBD), which causes gut pain, bleeding and diarrhoea. He had already been on a drug called Remicade (infliximab) for more than five years. This blocks the action of an inflammatory protein called tumour necrosis factor alpha (TNF alpha) in order to stop the immune system from attacking the colon wall. The problem is that drugs like this can have significant side-effects, such as leaving patients more prone to infections and, in rare cases, cancer. Another problem, Briggs tells me, is that the drugs stop working as people’s immune systems develop antibodies against them.

Briggs knew he couldn’t stay on infliximab for ever and he was tired of dealing with the cycle of flare-up and remission with his disease. Seeking a way to heal following a nasty flare-up during the summer of 2013, he sifted through more than 150 papers on anti-inflammatory supplements, diet and TNF blockers.

Eventually, he stumbled upon research suggesting that an antidepressant called bupropion has an effect on Crohn’s disease, another type of IBD where the immune system attacks the lining of the gut. Studies on mice had shown that instead of blocking the action of inflammatory proteins, bupropion appears to lower the production of those proteins in the first place.

Briggs decided to give it a try.

https://mosaicscience.com/story/off-label-antidepressants-prescribed-IBD-cancer-pain

 

[Alvin]

I'm surprised he would try this over fecal transplant

 

[Woolie]

It was an interesting article, raising all sorts of questions about whether off-label use of antidepressants is good or not.

My impression on reading the article was that there seemed to be a lot of different claims being made about a lot of different medicines. And they couldn't all be right. A lot of those apparent positive effects are probably just reporting artefacts (or as the article would say, placebo effects, but that word is so misused). The article itself hinted at this. Also, the fact that these drugs are so "safe" sounded telling to me. A bit too miraculous - drugs with really good effects and virtually no adverse effects. A bit too homeopathy-like.

Ever since I got ill, there's been some doctor trying to push tricyclic antidepressants like amitryptiline onto me, with claims that they will help everything from sleep to pain to whatever ails you. I haven't honestly seen much evidence of any of that. Amitryptiline is vaguely stupifying but paradoxically not that great at enhancing deep sleep. I'd prefer not to take drugs that aren't of clear benefit. I also wonder how many others have had a similar experience. Maybe the belief in these drugs may exist primarily in the heads of the doctors?

But I was interested in the bit about bupropion's possible anti-inflammatory effects - that did seem to have some basis.

 

[Alvin]

A lot of those apparent positive effects are probably just reporting artefacts (or as the article would say, placebo effects, but that word is so misused). The article itself hinted at this. Also, the fact that these drugs are so "safe" sounded telling to me. A bit too miraculous - drugs with really good effects and virtually no adverse effects. A bit too homeopathy-like.

I have talked about my real opinion of anti depressants on this forum before which led to complaints so i won't get into it again but keep in mind people consider them miracle drugs, and the fact the placebo fares so well means nothing to nobody, they want to believe.

 

[Trish]

I'm surprised he would try this over fecal transplant

Is there any evidence for fecal transplant as a treatment for ulcerative colitis? I've only ever seen it claimed as an effective treatment for Clostiridium difficile infection, which is completely different.

It's a long article. Another paragraph from it:

The story of how doctors discover new uses for antidepressants is usually the same, according to Jeffrey Jackson, professor of internal medicine at the Medical College of Wisconsin. Patients report to their doctors that more than just their depression has improved after taking a drug. This has happened in cases of people with dyspepsia, irritable bowel syndrome, chronic pelvic pain, chronic prostatitis, fibromyalgia, headaches and more.

He goes on to give examples like amitryptiline for pain. As he says at the end of the article, the trouble is, there's no money in clinical trials for re-purposed older drugs, so a lot of these claims have not been properly tested.

 

[Alvin]

Is there any evidence for fecal transplant as a treatment for ulcerative colitis? I've only ever seen it claimed as an effective treatment for Clostiridium difficile infection, which is completely different.

I googled it, found this
https://news.weill.cornell.edu/news...ffective-for-patients-with-ulcerative-colitis

 

[Arnie Pye]

People who have suffered from pain for many years can also be defensive if doctors suggest an antidepressant – they don’t want to be told the pain is all in their head. “I will say, ‘Listen, everything in the universe is in your head, pain is perceived in your brain.’”

Indeed, a growing body of evidence suggests that one of the more effective treatments for pain is cognitive behavioural therapy (CBT) – changing the way people think about pain to change the way it feels. Jackson’s argument to persuade patients is that antidepressants can work directly on their physical symptoms, but it will also help the depression that comes with physical misery.

If a patient is suffering from acute appendicitis and the appendix is about to blow, doctors don't prescribe anti-depressants and tell the patient the pain is perceived in their brain. There is a fundamental difference in attitude from doctors who are treating acute illness and those who are treating chronic pain, and the patients know it. The sub-text of a prescription for anti-depressants for pain for which no reason has been found is :

1) We (the doctors) think you're imagining it.

2) We are not going to look for a reason for your pain.

3) You (the patient) will be in pain for the rest of your life.

Of course the patients get upset and defensive. They've just been given a life-sentence!

 

[Dolphin]

Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.

https://www.ncbi.nlm.nih.gov/pubmed/28408193

Abstract
BACKGROUND:
Functional somatic syndromes, including chronic fatigue syndrome or irritable bowel syndrome, often co-exist. Treatment guidelines supported by high quality evidence exist for most functional somatic syndromes, but are lacking for multiple comorbid functional somatic syndromes. We aimed to assess the effect of the tricyclic antidepressant, imipramine, in patients with multiple functional somatic syndromes defined by the criteria for multiorgan bodily distress syndrome, a unifying diagnosis that encompasses most functional somatic syndromes and somatoform disorders.

METHODS:
In this single-centre, double-blind, randomised trial done in a Danish university hospital setting, participants were patients consecutively referred (age 20-50 years) fulfilling criteria for multiorgan bodily distress syndrome with no concurrent comorbid depression or anxiety disorder. Participants were randomly assigned (1:1) to receive either 10 weeks of low-dose imipramine or placebo (oral daily doses of 25-75 mg). The hospital pharmacy handled randomisation (computer-generated) and masking, providing sequentially numbered packs of study drug that were given serially to the participants.

All others involved were masked to allocation. Primary outcome was patient-rated overall health improvement on a 5-point clinical global improvement scale. Improvement was defined as patients responding "better" or "much better" as opposed to "unchanged" and "worse" or "much worse" when rating their overall health status after 10 weeks of minimum 25 mg study drug. Analyses included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01518634.

FINDINGS:
Between Jan 30, 2012, and Nov 24, 2014, 138 patients were randomly assigned; 70 to receive imipramine and 68 to receive placebo. The study was completed on May 1, 2015. 125 patients received at least one dose of study drug: 65 received imipramine and 60 received placebo. Treatment was terminated prematurely for eight (12%) patients receiving imipramine and seven (12%) patients receiving placebo. Data were missing for two (3%) patients receiving imipramine and three (5%) patients receiving placebo. Of the 120 patients (96%) who provided primary outcome data, 33 (53%) receiving imipramine reported their overall health status as "better" or "much better" compared with 14 patients (25%) receiving placebo.

The improvement after imipramine was significantly greater than after placebo (odds ratio 3·3 [95% CI 1·6-6·8]; p=0·001). Number needed to treat was 3·6 (95% CI 2·3-8·9). Analysis of the worst-case scenario for patients with missing outcome did not change the interpretation of the results. 32 patients (49%) receiving imipramine and 10 patients (17%) receiving placebo had at least one adverse event of moderate intensity (p=0·0001); eight patients (12%) receiving imipramine and three patients (5%) receiving placebo had at least one adverse event of severe intensity (p=0·1496). One patient (1%) receiving placebo experienced a serious adverse event (a subdural haematoma sustained after an accident). Adverse events caused dropout in four patients (6%) receiving imipramine and three patients (5%) receiving placebo.

INTERPRETATION:
Imipramine treatment compared with placebo significantly improved overall health in patients with multiple functional somatic syndromes when both treatments were supported by regular contacts with clinicians. Adverse events were more common in the imipramine group, but only rarely led to discontinuation of treatment.

---
A related tricyclic drug, trimipramine (Surmontil, Rhotrimine, Stangyl), has helped me with sleep and pain though my overall functioning remains low.

 

[Webdog]

It's worth mentioning the CDC's new caution on antidepressants for ME/CFS.

Some people with ME/CFS might benefit from antidepressants and anti-anxiety medications. However, doctors should use caution in prescribing these medications. Some drugs used to treat depression have other effects that might worsen other ME/CFS symptoms and cause side effects.

https://www.cdc.gov/me-cfs/treatment/index.html

In my personal experience, antidepressants are what many overworked doctors "go to" when they can't quickly figure out what is wrong with the patient. There is little chance that even an excellent doctor can properly diagnose and treat a chronic systemic disease based on symptoms in a 15 minute appointment.

Antidepressants provide a "treatment" without the time consuming task of actually practicing medicine.

 

[Sean]

Treatment guidelines supported by high quality evidence exist for most functional somatic syndromes,

Nah, they don't.

Imipramine treatment compared with placebo significantly improved overall health in patients with multiple functional somatic syndromes

Maybe just because it helped control pain.