Ultra-Low Doses of Opioids May Treat Suicidal Thoughts

Suicide leads to over 1 million deaths worldwide every year and is preceded by suicidal thoughts, although it is only rarely that suicidal thoughts lead to a completed suicide. Given the prevalence of suicide, the treatment of suicidal thoughts should be an important task for healthcare providers. However, there are currently no short term, medication based treatments for suicidal thoughts that can be easily administered independently in an outpatient setting and which can be effective for a wide range of patients. Therefore, one study was designed to test the effectiveness of very low doses of the opioid buprenorphine in quickly treating suicidal thoughts.

The study followed 88 patients selected from the populations of four medical centers in Israel. Participants were selected based on their suffering from clinically significant suicidal ideation and could not have a history of opioid abuse. 57 patients received buprenorphine treatment while 31 received a placebo, and both groups had their amount of suicidal thoughts as well as their likelihood to commit suicide measured over the course of four weeks. At the end of the study, patients in the buprenorphine group had a significant decrease in suicidal thoughts compared to the placebo group, although this group also exhibited an increased number of side effects, particularly fatigue, nausea, dry mouth, and constipation. At the end of the study, both groups were slowly tapered off of their medications, and no participant in either group reported feeling withdrawal symptoms. This study suggests that buprenorphine may be an effective short term treatment of suicidal thoughts. Although it is important to treat suicidal thoughts, is doing so by increasing the number of prescribed opioids the most effective method of doing this?

 

Yovell Y, Bar G, Mashiah M. Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry. DOI:10.1176/appi.ajp.2015.15040535

Antidepressants may double the risk of aggression and suicide in children

It is has been researched that suicidal behavior may be increased with children aged <18 who take popular antidepressants such as SSRIs and SNRIs, however, few systemic research has been done to correlate the effects of aggressive behavior with popular antidepressants.  This systematic review and meta-analysis was conducted to analyze the mortality, suicidality, aggression, and akathisia associated with five popular antidepressants—duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine—using clinical study reports.  Akathisia is an extreme state of restlessness, agitation, and distress that can increase the risk of suicide and violence. No patients were involved in the study.  The methods included obtaining clinical study reports from the European Medicines Agency and Modern Humanities Research Association.  Out of the 198 clinical study reports, only 68 were used.  Using the reports that contained double bind placebo controlled trials and patient narratives, primary outcomes (mortality and suicide) and secondary outcomes (aggressive behavior and akathisia) were assessed by searching for specific terms, such as those used by the FDA.

Quality of the clinical study reports were varied, such as the number of trials conducted and the length of the study designs.  The results of the study showed that 16 deaths occurred in adults, and 155 suicidality events occurred with an odds ratio in children and adolescents doubled to that in adults.  The odds ratio for children and adolescents was also double that to adults for aggressive behavior.  The odds of akathisia were roughly the same for both adults and children and adolescents.  Thus, the data from this study shows that there is indeed an increased risk of suicide in children and adolescent taking antidepressants.  However, the study also found that there was a significant increase in aggressive behavior in children and adolescents.  This was a comprehensive review of randomized controlled trial data and is the first to note this finding of increased aggressive behavior.

My questions posed to colleagues are: Do you feel that this is a significant, valuable finding, despite the limitations in the research study?  Do you feel that this information could benefit pharmacists, and if so, how?

BMJ. 2016; 352(65): .