Changes in the consumption of antiepileptics and psychotropic medicines after starting low dose naltrexone: A nation-wide register-based controlled before-after study

Abstract

In this controlled before-after study based on data from the Norwegian Prescription Database, we examine whether starting off-label use of Low Dose Naltrexone (LDN) is followed by changes in the consumption of psychotropic medicines including antiepileptics. Patients that collected LDN for the first time in 2013 (N = 11247) were included and stratified into three groups based on LDN exposure. We compared differences in means of cumulative number of defined daily doses (DDD) as well as changes in the number of users one year before and one year after starting LDN. There was a dose-response association between increasing LDN exposure and reductions in the number of users of antiepileptics, antipsychotics and antidepressants. There were significant difference-in-differences in DDDs between the groups with the lowest and highest LDN exposure of antipsychotics (1.4 DDD, 95% CI 0.4 to 2.3, p = 0.007), and in number of users of antiepileptics (3.1% points, 95% CI 1.6% to 4.6%, p < 0.001), antipsychotics (2.1% points, 95% CI 1.2% to 3%, p < 0.001), and antidepressants (2.8% points, 95% CI 1.1% to 4.4%, p = 0.001). The findings show an association between the initiation of persistent LDN use and reduced consumption of several psychotropic medicines and antiepileptics. Beneficial effects of LDN in the treatment of psychiatric diseases cannot be ruled out.

Depression in Fibromyalgia Patients May Require Low-Dose Naltrexone to Respond: A Case Report

“…The current FDA-approved medications have no effect on the endogenous opioid system in contrast to naltrexone that we used off-label with success. Naltrexone was actually associated with reductions of the psychotropic regimen [ 17 ], as highlighted in our case by the discontinuation of an antidepressant and benzodiazepine and decrease in gabapentin dose while achieving remission of chronic pain and depression.…”

Reported Benefits of Low-Dose Naltrexone Appear to Be Independent of the Endogenous Opioid System Involving Proopiomelanocortin Neurons and β-Endorphin

“…The reported efficacy for low-dose naltrexone (LDN) is paradoxical; MOR agonists, not antagonists, convey analgesic and rewarding properties that can be blocked by application of antagonists. Nonetheless, many anecdotal reports ( Ramanathan et al, 2012 ; Chopra and Cooper, 2013 ; Ghai et al, 2014 ; Leonard et al, 2017 ; Bolton et al, 2020 ; Zappaterra et al, 2020 ), post hoc studies ( Ludwig et al, 2016 ; Raknes and Småbrekke, 2017 , 2019 ; Raknes et al, 2018 ), and limited clinical trials ( Younger and Mackey, 2009 ; Younger et al, 2013 ; Brewer et al, 2018 ; Lie et al, 2018 ) suggest that LDN may be useful for treating chronic pain and inflammation. Further, in many of these studies patients report effects such as improved feelings of well-being and vivid dreams ( Younger and Mackey, 2009 ; Younger et al, 2013 ; Brewer et al, 2018 ; Lie et al, 2018 ; Bolton et al, 2020 ; Zappaterra et al, 2020 ), and recently LDN has been tested as an adjunct therapy for patients living with depression ( Mischoulon et al, 2017 ) with some promising preliminary results.…”