Suicide Therapy: Opioids Celebrate Comeback

15. March 2016
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Suicides often mark the end of a mental health history. Researchers have discovered other risk factors and other approaches for treating suicidal people the as well. Now opioids are making a comeback. They might soon enrich the therapeutic portfolio.

The estimated number of people who die from suicide is unknown. In addition to known risk factors such depressive disorders and psychosis, accidents also play a role, Donald A. Redelmeier from Toronto reports.

Shocking realisation

Redelmeier analysed the records of 235,110 patients who had had concussion as part of a cohort study. The respective data came from the Ontario Health Insurance Plan, a health insurance company operating in the Canadian province of the same name. As Redelmeier found out, 168,188 people had no other risk factors, ie no psychological pre-existing conditions. In this group, 667 people took their own lives within 9.3 years. This corresponds to the equivalent of 31 suicides per 100,000 population per year. WHO researchers provide data stating a population average of 9.8 cases per 100,000 population per year. Looking at concussions suffered by recreational weekend athletes, Redelmeier even calculated 39 suicides per 100,000 population per year. The scientist however offers no plausible explanations.

Stomach with bugs

Redelmeier’s colleagues from Toronto have come across another trail. Junaid Bhatti from Toronto examined data from 8,815 patients who had undergone bariatric surgery due to obesity. According to older studies, the suicide rate is four times higher than among the general population, something which Bhatti was fully able to confirm. Before the respective medical interventions he found 2.33 suicides per 1,000 person-years; afterwards it was 3.63. Psychiatrists primarily consider psychiatric comorbidities accompanying obesity to be the reason for this. The American Society for Metabolic and Bariatric Surgery has long been calling for psychiatric examinations to be carried out on patients before surgery, but this call has as yet not managed to be sufficiently well heard.

An oldie returns

Opportunities for intervention become all the more important. In the guideline, “Suicidality in children and adolescents” – a guideline in need of revision – doctors write “Restraint should be exercised when prescribing a medication which cannot be monitored and is potentially dangerous”. Opioids are also included in this category. Before the introduction of modern tricyclics, patients with severe depression often received opioids. Yoram Yovell from Haifa has made use of data derived from animal experiments: when scientists separated individual animals from their group, low-dose opioids eased the associated pain of separation. This effect has now been investigated in humans by Yovell. He took 62 patients with severe suicidal ideation into his study. All participants scored eleven or more points on the Beck Suicidal Scale (BSS). The average was almost 20 points; maximum possible points is 38. These numbers concealed borderline personality disorders. adjustment disorders and depressions but included no addiction problems.

Yovell administered low doses of buprenorphine as an adjunct to existing pharmacotherapy. He chose 0.1 to 0.2 milligrams per day. In pain management physicians use 0.6 to 1.6 milligrams per day. It was no mere accident that his choice was buprenorphine. In the event of a deliberately induced overdose, this active agent exhibits fewer side effects than other opioids. Every third patient only received a placebo. Intake of psychiatrist-prescribed medications continued. After four weeks, the BSS score for the verum group decreased significantly, by 7.1 points. Both the placebo and the opioid group each included one suicide attempt. Typical opioid side effects occurred despite the low dosage. These included gastrointestinal symptoms, fatigue and dry mouth. Despite these promising results Yovell’s work has one catch: Scientists cannot say anything about the long-term effects involved.

Wrestling over receptors

Alan F. Schatzberg of the Stanford School of Medicine therefore urges larger studies of longer duration. He writes in a commentary, in assessing its added value, that the risk of becoming dependent on the medication needs to be taken into account. Schatzberg sees great opportunities to use ALKS 5461, ie. buprenorphine plus Samidorphan. The opioid antagonist blocks μ-opioid receptors, but not δ- or κ receptors. This will help in preventing drug dependencies. From a scientific perspective, the chances are good. Following extensive preparatory work in mid 2014 Alkermes, the producer, started the FORWARD-5 study (Study A of ALKS 5461 for the Treatment of Major Depressive Disorder). Pharmacologists are testing their medication in low and high dose versus placebo. Alkermes anticipates having the first results in July 2016.

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Dr Anthony Murawski
Dr Anthony Murawski

p.s. I posted my message before checking for spelling errors. I don’t know how to edit the original response.

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Dr Anthony Murawski
Dr Anthony Murawski

After no psychiatrists were able to help me manage severe-to-extreme, chronic depression (per HMDS), I knew I would die unless I began researching the medical literature myself during remissions. I had no background in medicine or life sciences, so I had to educate myself in the field of psychoneuroimmunology. I discovered that my wife and I both had symptoms of Lyme disease. We were tested. The results showed with 100% specificity that we both had active infections of Lyme disease. Borrelia burgrdorferi, the bacterium that causes Lyme disease, is remarkably similar from a morphological standpoint to Treponoma palidum, which causes syphilis. Before penicillin was discovered, approximately 25% of patients at mental institutions in the United States were infected with syphilis. In the U.S., an epidemic of Lyme disease is occurring, with hundreds of thousands of new cases annually. People who are infected are typically undiagnosed, misdiagnosed, or less often, diagnosed but inadequately treated. I recommend Cure Unknown: Inside the Lyme Epidepic, by Pam Weintraub, who is a senior editor at Discover Magazine. Her book explains why the Centers for Disease Control and the Infectious Diseases Society of America attempt to minimize the rates of infection and scope of symptoms, while falsely claiming that the infection is easily identified and easily cured. The people who wrote the testing and treatment guidelines have patent rights in the highly inaccurate commercial test kits that they recommend be used. My depression is likely caused by 46 years of cerebral infection with Borrelia burgdorferi and Babesia duncani or microti (same class of pathogens as malaria). I was infected far too long to get any results with animicrobial treatment. That is the one thing in Ms. Weintraub’s book that should be corrected: people who have been infected for decades with this pathogen, with advanced symptoms, are likely to deteriorate as a result of aggressive antimicrobial treatment due to a massive, Jarisch-Herxheimer-like reaction. That is exactly what happened to me, and many other people I’ve communicated with. Neither buprenorphine nor ketamien alone were sufficient to manage my depression. When I was close to death in 2011, I discovered that buprenorphine prevents tolerance to ketamine (sample size 1), and that both medications act synergistically as antidepressants — probably because they are both mu-opoid receptor agonists. Ketamine has potent anti-inflammatory effects, reducing cerebral levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). This is why it is effective for depression, unlike memantine, which does not inibhibit inflammtory signalling. Chronic inflammatory signalling causes neurotoxicity (excitotoxicity) via the kynurenine pathway, as well as oxidative stress leading to mitochondrial damage, and severe dysfunction of the adaptive immune response that is not even detected by standard serological testing of immune system markers. I have been in remission from severe/extreme depression for over four years because I found a psychiatrist who recognized I could not survive any longer, and was willing to try a combination of intramuscular ketamine and sublingual buprenorphine. The dosages of my medications have remained unchanged for over four years. [Comment shortened by editorial team.]

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