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      The effectiveness of different singly administered high doses of buprenorphine in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence: a randomized, double-blind, clinical trial

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      , ,
      Trials
      BioMed Central
      Buprenorphine, Suicidal ideation, Opioid dependence

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          Abstract

          Background

          Buprenorphine is usually administered to treat opioid use disorder and pain syndromes. This research presents the first study regarding the effectiveness of different singly administered high doses of buprenorphine (a partial opioid agonist (of μ-opioid receptors), a potent opioid antagonist (of κ-receptors) and a partial agonist of nociception receptors) in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence. It follows small studies that suggest that ultra-low-dose buprenorphine may be useful in reducing suicidal ideation. The goal of this study was to describe the outcome of different doses of buprenorphine on suicidal opioid-dependent patients over a 3-day interval, by conducting a randomized clinical trial.

          Methods

          Fifty-one suicidal male inpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for both opioid dependence and major depressive disorder were randomized to three groups ( n = 17 per group) to receive a single, sublingual dose of buprenorphine (32 mg, 64 mg, or 96 mg). Out of 51 participants, there were 47 patients; 16 (34.04%) received 32 mg, 17 (36.17%) received 64 mg, and 14 (29.78%) received 96 mg of sublingual buprenorphine. They were evaluated by using psychometric assessment of the Beck Scale for Suicidal Ideation (BSSI) and interviews based on DSM-5 criteria. A placebo group was not included because of the high probability of severe withdrawal without active pharmacological treatment. The study was conducted with appropriate precautions and monitoring of respiratory and cardiovascular measures. The medication was administered while the patients were in moderate opiate withdrawal, as indicated by the presence of four to five withdrawal symptoms. A structured clinical interview was conducted, and urine toxicology testing was performed.

          Results

          Patients completed the 3-day trial course. The outcomes illustrated a significant reduction in BSSI scores within each of the three groups, p < 0.01., but no difference in results between the groups, p = 0.408.

          Conclusions

          The results suggest that a single high dose of buprenorphine could rapidly treat suicidal ideations. A single high dose of buprenorphine may be a main-mechanism medication that gives a rapid treatment for suicidal opioid-dependent patients. Placebo-controlled trials are required to measure the safety and the physiological and psychological effects of this medication.

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          Most cited references35

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          Scale for Suicide Ideation: psychometric properties of a self-report version.

          A self-report version of the Scale for Suicide Ideation (SSI) was administered to 50 inpatients diagnosed with mixed DSM-III psychiatric disorders and 55 outpatients with affective disorders. The self-report SSI was written for both paper-and-pencil and computer administration. The correlations between the self-reported and clinically rated versions for both inpatients and outpatients were greater than .90, which suggests strong concurrent validity. The Cronbach coefficient alphas for the paper-and-pencil and computer versions were also in the .90s and indicated high internal consistency. Furthermore, the mean SSI scores of the computer version for both the inpatients and outpatients were higher than the mean SSI scores of the clinical ratings; the patients described more severe suicide ideation than clinicians reported.
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            The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse.

            Initial hypotheses regarding the role of the kappa opioid system in drug addiction suggested that kappa receptor stimulation had anti-addictive effects. However, recent research suggests that kappa receptor antagonists may reverse motivational aspects of dependence. In the present review, we revisit the studies that measured the effects of kappa receptor ligands on the reinforcing and rewarding effects of drugs and postulate underlying neurobiological mechanisms for these effects to elaborate a more complex view of the role of kappa receptor ligands in drug addiction. The review of studies indicates that kappa receptor stimulation generally antagonizes the acute reinforcing/rewarding effects of drugs whereas kappa receptor blockade has no consistent effect. However, in a drug dependent-like state, kappa receptor blockade was effective in reducing increased drug intake. In animal models of reinstatement, kappa receptor stimulation can induce reinstatement via a stress-like mechanism. Results in conditioned place preference/aversion and intracranial self-stimulation indicate that kappa receptor agonists produce, respectively, aversive-like and dysphoric-like effects. Additionally, preclinical and postmortem studies show that administration or self-administration of cocaine, ethanol, and heroin activate the kappa opioid system. kappa receptor agonists antagonize the reinforcing/rewarding effects of drugs possibly through punishing/aversive-like effects and reinstate drug seeking through stress-like effects. Evidence suggests that abused drugs activate the kappa opioid system, which may play a key role in motivational aspects of dependence. Kappa opioid systems may have an important role in driving compulsive drug intake.
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              A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department.

              We examined the preliminary feasibility, tolerability and efficacy of single-dose, intravenous (i.v.) ketamine in depressed emergency department (ED) patients with suicide ideation (SI). Fourteen depressed ED patients with SI received a single i.v. bolus of ketamine (0.2 mg/kg) over 1-2 min. Patients were monitored for 4 h, then re-contacted daily for 10 d. Treatment response and time to remission were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Kaplan-Meier survival analysis, respectively. Mean MADRS scores fell significantly from 40.4 (s.e.m.=1.8) at baseline to 11.5 (s.e.m.=2.2) at 240 min. Median time to MADRS score ≤10 was 80 min (interquartile range 0.67-24 h). SI scores (MADRS item 10) decreased significantly from 3.9 (s.e.m.=0.4) at baseline to 0.6 (s.e.m. =0.2) after 40 min post-administration; SI improvements were sustained over 10 d. These data provide preliminary, open-label support for the feasibility and efficacy of ketamine as a rapid-onset antidepressant in the ED.
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                Author and article information

                Contributors
                jamshid_ahmadi@yahoo.com
                Journal
                Trials
                Trials
                Trials
                BioMed Central (London )
                1745-6215
                29 August 2018
                29 August 2018
                2018
                : 19
                : 462
                Affiliations
                ISNI 0000 0000 8819 4698, GRID grid.412571.4, Substance Abuse Research Center, , Shiraz University of Medical Sciences, ; Shiraz, Iran
                Article
                2843
                10.1186/s13063-018-2843-9
                6114789
                30157924
                b5ad940f-6516-4782-ba94-8fb228b55954
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 September 2017
                : 6 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004320, Shiraz University of Medical Sciences;
                Award ID: IR.SUMS.REC.1395.102,
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Medicine
                buprenorphine,suicidal ideation,opioid dependence
                Medicine
                buprenorphine, suicidal ideation, opioid dependence

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