title: Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial.
abstract: 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.
  
  
  METHODS
  This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment.
  
  
  RESULTS
  Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference -4.3, 95% CI=-8.5, -0.2) and after 4 weeks (mean difference=-7.1, 95% CI=-12.0, -2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial.
  
  
  CONCLUSIONS
  The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment.
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Yovell
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Gali
authors.initials: G
authors.lastname: Bar
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Moti
authors.initials: M
authors.lastname: Mashiah
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Baruch
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Irina
authors.initials: I
authors.lastname: Briskman
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Jack
authors.initials: J
authors.lastname: Asherov
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Amit
authors.initials: A
authors.lastname: Lotan
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Amihai
authors.initials: A
authors.lastname: Rigbi
authors.affiliation: From the Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel; the Abarbanel Mental Health Center, Bat Yam, Israel; the Wolfson Medical Center, Holon, Israel; the Department of Psychiatry, Hadassah Medical Organization, Jerusalem, Israel; Kinneret Academic College on the Sea of Galilee, Israel; Beit Berl Academic College, Kfar-Sava, Israel; and the Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman.
authors.forename: Jaak
authors.initials: J
authors.lastname: Panksepp
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000523:psychology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011619:Psychotropic Drugs / Q000627:therapeutic use; D059020:Suicidal Ideation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D011619:Psychotropic Drugs; D002047:Buprenorphine