This post will consist of an overview of one particular research report, and some of my thoughts about it. Here is the citation of the paper I’ll be discussing:
Yovell, Y., Bar, G., Mashiah, M., Baruch, Y., Briskman, I., Asherov, J., Lotan, A., Rigbi, A. & Panksepp, J. (2016). Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial. American Journal of Psychiatry. 173:5.
Numerous things in this article concern me. I’ve been meditating on it since around 2017. At this point I’ve decided to share the citation for the paper, quotations from the article that draw my particular attention, and some of my thoughts about those quotations.
Here’s the study objective from the top of the first page.
Objective: Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation.
Here’s the study population
The study was performed on “Severely suicidal patients without substance abuse…”
Here’s the study intervention
The study examined “…ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily)…”
The results
Participants in the experimental group receiving buprenorphine “…had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference 24.3, 95% CI=28.5, 20.2) and after 4 weeks (mean difference=27.1, 95% CI=212.0, 22.3).”
Statements about history, rationale, and safety
Opioids were widely used to treat depression from about 1850 to 1956. Because of their addictive potential and lethality in overdose, opioids were replaced by standard antidepressants once these became available. However, several studies since then have found them to be effective for treating depression.
Read those sentences again. I find that passage particularly odd.
Opioids are involved in more deaths than any other drug class in fatal pharmaceutical overdoses in the United States. Thus, the lower lethality of buprenorphine and the very low dosages employed in this study were crucial for enabling its independent, home-based use. However, buprenorphine is potentially addictive and possibly lethal. We therefore designed this study as a time-limited trial for severely suicidal patients without substance abuse.
Exclusion criteria were a lifetime history of opioid abuse…substance or alcohol abuse within the past 2 years, and benzodiazepine dependence within the past 2 years.
Adherence to the protocol
“Outpatients received the study medication for the following week during their weekly visits, and took it independently at home. Average adherence, measured by pill counts, was 92%.”
Comorbidities
“More than half (56.8%) met criteria for borderline personality disorder…”
Clinical history vs. follow-up
“All participants denied withdrawal symptoms during their follow-up appointment 1 week later. It is possible that in this opioid-naive population, the short duration and low dosages protected against dependence.”
The bottom line
“In this study, the time-limited use of very low dosages of buprenorphine was associated with a decrease in severe suicidal ideation.”
Required disclosure
“Dr. Yovell reports being listed as an inventor on a patent application for the use of low-dose buprenorphine for suicidality; he has assigned his rights in the patent to the University of Haifa but will share a percentage of any royalties that may be received by the university.”
The following points have also occurred to me over my years of considering this study:
In conclusion I’ll say that this paper was one of the research reports that developed my focus some years ago on what I simply call “Harms of Use”. That focus led to me gather such papers (and related papers) over a series of a few years, read and study them, and prepare materials for education, training, etc. based on their content.
References
Hart, B. & Jaccard, J. (2006). Arbitrary Metrics in Psychology. American Psychologist. 61(1): 27-41.
Ioannidis, J. P. A. (2006). Why Most Published Research Findings Are False. PLoS Medicine. 2(8) e: 124. DOI: 10.1371/journal.pmed.0020124
Suggested Reading
DeWall, C. N., Chester, D. S. & White, D. S. (2015). Can Acetaminophen Reduce the Pain of Decision-Making? Journal of Experimental Social Psychology. 56:117–120.
DeWall, C. N., MacDonald, G. M., Webster, G. D., Masten, C. L., Baumeister, R. F., Powell, C., Combs, D., Schurtz, D. R., Stillman, T. F., Tice, D. M. & Eisenberger, N. I. (2010). Acetaminophen Reduces Social Pain: Behavioral and neural evidence. Psychological Science. 21(7):931-937. DOI: 10.1177/0956797610374741
Durso, G. R. O., Luttrell, A. & Way, B. M. (2015). Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen blunts evaluation sensitivity to both negative and positive stimuli. Psychological Science. 26(6):750–758. doi:10.1177/0956797615570366.
Maughan, B. C., Hersh, E. V., Shofer, F. S., Wanner, K. J., Archer, E., Carrasco, L. R. & Rhodes, K. V. (2016). Unused Opioid Analgesics and Drug Disposal Following Outpatient Dental Surgery: A randomized controlled trial. Drug and Alcohol Dependence. 168(1): 328-334.
Randles, D., Heine, S. J. & Santos, N. (2013). The Common Pain of Surrealism and Death: Acetaminophen reduces compensatory affirmation following meaning threats. Psychological Science. 24(6) 966 –973.