Clinical Efficacy and Safety Profile of Lofexidine Hydrochloride in Treating Opioid Withdrawal Symptoms: A Review of Literature

Rehman, Saif Ur; Maqsood, Muhammad Haisum; Bajwa, Hamza; Din, Asim Tameez Ud; Malik, Mustafa Nadeem

doi:10.7759/cureus.4827

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Opioid-free treatments have been used in clinical settings to control withdrawal symptoms in abstaining patients [6]. Alpha-adrenergic agonists, such as lofexidine [67], clonidine or tizanidine [68], have been shown to be superior to placebo control to decrease anxiety and autonomic hyperactivity, but not as effective as opioid-based treatments in maintaining abstinence. Such agents are also used prudently as they might produce hypotension in these patients [24,68,6].…”

Section: Potential Non-opioid Treatments For Oudmentioning

confidence: 99%

Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date

Chalhoub

Kalivas

2020

Drugs

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Opioid use disorder (OUD) represents a major public health problem that affects millions of people in the United States and worldwide. The relapsing and recurring aspect of OUD, driven by lasting neurobiological adaptations at different reward centers in the brain, represents a major obstacle towards successful long-term remission from opioid use. Currently, three drugs that modulate the function of the opioidergic receptors, methadone, buprenorphine and naltrexone, have been approved by the US Food and Drug Administration (FDA) to treat OUD. In this review, we discuss the limitations and challenges associated with the current maintenance and medicationassisted withdrawal strategies commonly used to treat OUD. We further explore the involvement of glutamatergic, endocannabinoid and orexin signaling systems in the development, maintenance and expression of addiction-like behaviors in animal models of opioid addiction, and as potential and novel targets to expand therapeutic options to treat OUD. Despite a growing preclinical literature highlighting the role of these potential targets in animal models of opioid addiction, clinical and translational studies for novel treatments of OUD remain limited and inconclusive. Further preclinical and clinical investigations are needed to expand the arsenal of primary treatment options and adjuncts to maximize efficacy and prevent relapse.

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Section: Potential Non-opioid Treatments For Oudmentioning

confidence: 99%

Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date

Chalhoub

Kalivas

2020

Drugs

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“…The sympatholytic α-2 agonists lofexidine and clonidine have been implicated as potential alternatives or adjuncts to long-acting opioids. 6,7 Although this connection has led to considerations in the pharmacology of opioid withdrawal, to our knowledge, it has rarely been discussed in the context of cardiac complications such as TCM.…”

Section: Introductionmentioning

confidence: 99%

The Connection Between Opioid Withdrawal and Takotsubo Cardiomyopathy: Case Reports of ‘Opioid Octopus Heart’

Hack

Ojeniyi

Mamzhi

et al. 2022

Georgetown Medical Review

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Case PresentationsHere, we present 2 cases of TCM in patients who chronically used opioids, both at the same institution within 1 month of each other. The first patient is a 68-year-old man who presented with a chronic obstructive pulmonary disease exacerbation and did not disclose his long-standing opioid use disorder. One day after admission, he was found to be in opioid withdrawal and, soon after, developed TCM. He was originally treated for non-ST elevation myocardial infarction and opioid withdrawal but decompensated. He was sent to the intensive care unit (ICU) to receive pressors and fluid resuscitation. He soon recovered and his cardiac function returned to baseline. The second patient is a 33-year-old woman with opioid use disorder taking methadone who presented with lower extremity weakness, edema, and pain. She was diagnosed with infective endocarditis. While awaiting surgery and receiving antibiotics, she developed respiratory failure and was upgraded to the ICU. There was a lapse in her opioid treatment, and she subsequently developed TCM. She was treated with pressors and fluids in the ICU, and eventually recovered with reduced cardiac function at the time of discharge. ConclusionsWhile clinical evidence indicated opioid withdrawal as the likely provoking factor for development of TCM in the first case, the second patient's symptoms from other clinical complications confounded the cause of her TCM. Twelve similar cases have been reported in the literature, suggesting that opioid withdrawal may be associated with development of TCM. Further quantitative research is required to establish this relationship. Our findings contribute to the theoretical pathophysiology of TCM and offer important considerations for clinical management of opioid withdrawal.

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“…To prevent relapse by reducing the intensity and duration of opioid withdrawal symptoms, a variety of different medications are used, including alpha-2 adrenergic agonists (clonidine or lofexidine), and adjuvant agents that help mitigate individual symptoms of opioid withdrawal such as non-steroidal anti-inflammatory agents (NSAIDs) against pain (e.g., ibuprofen), antihistamines (e.g., hydroxyzine), anti-emetics against nausea (e.g., ondansetron), and anti-diarrheal drugs (e.g., loperamide). Double-blind, placebo-controlled randomized trials in humans have shown that both clonidine and lofexidine are effective in mitigating opioid withdrawal symptoms (Rehman et al 2019 ; Alam et al 2020 ). However, a high incidence of adverse effects is commonly reported for both treatments, including sedation, dry mouth, hypotension, drowsiness, and dizziness (Gowing et al 2014 ; Hussain et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Functional observation after morphine withdrawal: effects of SJP-005

Verster

Scholey

Dahl³

et al. 2021

Psychopharmacology

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Rationale and objective SJP-005 (ketotifen and ibuprofen) is being developed as a potential new treatment for opioid withdrawal. Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2–12) effects of SJP-005 on discontinuation-induced morphine withdrawal. Methods Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice daily, oral dosages of placebo or SJP-005 (1 mg/kg ketotifen and 15 mg/kg ibuprofen) were administered starting 4 days before (study 1), 2 days before (study 2), or immediately after (study 3) morphine cessation. Functional observations were made up to 12 h after treatment cessation on day 19 (early phase), and immediately after treatment on days 20–30 (late phase). Treatment effects (mean overall score, and individual symptoms) were compared with placebo using ANOVA, and Tukey’s tests in case of multiple comparisons. Results Across the studies, the number of withdrawal signs on day 19 (early phase) and days 20–30 (late phase) was lower with SJP-005 compared with placebo. The effects of SJP-005 when treatment was initiated 2 days before morphine cessation by discontinuation were most pronounced and statistically significant in the late phase (F(1,18) = 14.10, p = 0.001). In particular, a significant reduction was observed in hypersensitivity to touch (F(1,18) = 13.65, p = 0.002). A 50% reduction in withdrawal symptoms was observed 9.0 days after placebo versus 4.5 days after SJP-005. After 9.0 days, all withdrawal symptoms were absent in the SJP-005 group, while symptoms in the placebo group were still evident on day 18. Conclusion Compared to placebo, SJP-005 significantly reduced the incidence and duration of discontinuation-induced morphine withdrawal symptoms when treatment was initiated 2 days before morphine cessation.

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Clinical Efficacy and Safety Profile of Lofexidine Hydrochloride in Treating Opioid Withdrawal Symptoms: A Review of Literature

Cited by 8 publications

References 32 publications

Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date

Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date

The Connection Between Opioid Withdrawal and Takotsubo Cardiomyopathy: Case Reports of ‘Opioid Octopus Heart’

Functional observation after morphine withdrawal: effects of SJP-005

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