Suchergebnisse

Abstract

Aims
We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone.


Methods
Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD).


Results
In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial.


Conclusion
These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

BACKGROUND: Consensus guidelines recommend multimodal chronic pain treatment with increased use of non-pharmacological treatment modalities (NPM), including as first-line therapies. However, with many barriers to NPM uptake in US healthcare systems, NPM use may vary across medical care settings. Military veterans are disproportionately affected by chronic pain. Many veterans receive treatment through the Veterans Health Administration (VHA), an integrated healthcare system in which specific policies promote NPM use. OBJECTIVE: To examine whether veterans with chronic pain who utilize VHA healthcare were more likely to use NPM than veterans who do not utilize VHA healthcare. DESIGN: Cross-sectional nationally representative study. PARTICIPANTS: US military veterans (N = 2,836). MAIN MEASURES: In the 2019 National Health Interview Survey, veterans were assessed for VHA treatment, chronic pain (i.e., past 3-month daily or almost daily pain), symptoms of depression and anxiety, substance use, and NPM (i.e., physical therapy, chiropractic/spinal manipulation, massage, psychotherapy, educational class/workshop, peer support groups, or yoga/tai chi). KEY RESULTS: Chronic pain (45.2% vs. 26.8%) and NPM use (49.8% vs. 39.4%) were more prevalent among VHA patients than non-VHA veterans. After adjusting for sociodemographic characteristics, psychiatric symptoms, physical health indicators, and use of cigarettes or prescription opioids, VHA patients were more likely than non-VHA veterans to use any NPM (adjusted odds ratio [aOR] = 1.52, 95% CI: 1.07–2.16) and multimodal NPM (aOR = 1.80, 95% CI: 1.12–2.87) than no NPM. Among veterans with chronic pain, VHA patients were more likely to use chiropractic care (aOR = 1.90, 95% CI = 1.12–3.22), educational class/workshop (aOR = 3.02, 95% CI = 1.35–6.73), or psychotherapy (aOR = 4.28, 95% CI = 1.69–10.87). CONCLUSIONS: Among veterans with chronic pain, past-year VHA use was associated with greater likelihood of receiving NPM. These findings may suggest that the VHA is an important ...