(56) Nonpharmacologic Interventions Ameliorate Withdrawal Signs in Opioid-Dependent Adults

Background & Introduction: The severity of opioid withdrawal is typically assessed in clinical settings using the Clinical Opiate Withdrawal Scale (COWS), which comprises both subjective symptoms (ex. restlessness, muscle aches) and objective signs (ex. pulse elevation, sweating).1 Other scales like the Subjective Opiate Withdrawal Scale (SOWS) may also be used.2 For mild-to-moderate opioid withdrawal (COWS scores of 5-12 and 13-24, respectively),1 current recommendations include administering opioid agonists such as buprenorphine and methadone along with adjunctive medications for symptom control.3 However, outside of the neonatal opioid withdrawal syndrome literature,4 there is little guidance about providing nonpharmacological interventions as adjunctive therapies for people in opioid withdrawal.

We describe here some unexpected observations regarding the course of opioid withdrawal that we made in methadone-maintained patients with opioid use disorder (OUD) while piloting a clinical trial for a potential new opioid agonist therapy. We withheld the usual scheduled methadone doses of our two pilot participants for two consecutive days prior to each study session in order to produce mild-to-moderate opioid withdrawal. We then observed their subsequent clinical course after administration of the experimental study drug, a negative control (placebo), or a positive control drug (oxycodone 30 mg) in separate single-blind sessions.

Case Description: Participant #1: 41-year-old male with past medical history of moderate OUD (on methadone 120 mg/day), ongoing sporadic fentanyl use, cocaine use, amphetamine use, depression, chronic pain, acid reflux, and mild tobacco use disorder. Prior to methadone withholding, baseline COWS=0 (no withdrawal) and SOWS=0 (no withdrawal). After missing two methadone doses, initial SOWS=16 (moderate withdrawal) and COWS=8 (mild withdrawal) prior to beginning Session #1, both of which had a sustained decrease to 0-2 (no or mild withdrawal) after administration of the positive control (oxycodone). Patient also received one dose of acetaminophen for muscle aches and several nonpharmacologic interventions to make him more comfortable, including a cold pack, cold water, lights turned down, and recumbent positioning in a reclining chair. Pupil size remained constant until the patient received his methadone dose at the end of the session. For Session #2, initial SOWS=15 (moderate withdrawal) and COWS=11 (mild withdrawal). Both scores transiently decreased to 0 (no withdrawal) at 90 minutes post-placebo, with corresponding pupil size decrease of 1 mm in both eyes. A subsequent rebound partial increase in COWS to 5-7 (mild withdrawal) and pupil size occurred until administration of his usual methadone dose, but we observed a sustained decrease in SOWS of 1-3 (mild withdrawal) throughout the session.

Participant #2: 41-year-old female with past medical history of severe OUD (on methadone 120 mg/day), ongoing sporadic fentanyl use, severe tobacco use disorder, cocaine use, benzodiazepine use, amphetamine use, depression, anxiety, hypothyroidism (controlled on levothyroxine), acid reflux, obesity, hyperlipidemia, and chronic bronchitis. Prior to methadone withholding, baseline COWS=0 and SOWS=0 (no withdrawal for both). After missing two methadone doses, initial SOWS=16 (moderate withdrawal) and COWS=11 (mild withdrawal) prior to beginning Session #1, which decreased to SOWS=5-9 (mild withdrawal) and COWS=3-7 (mild withdrawal) after administration of positive control. Patient also received several nonpharmacologic interventions, including a fan blowing on her, lights turned down, cold water, and recumbent positioning in a reclining chair. Pupil size remained constant until the patient received her methadone dose at the end of the session. For Session #2, initial SOWS=12 (moderate withdrawal) and COWS=11 (mild withdrawal). Both scores transiently decreased to SOWS=2 (mild withdrawal) and COWS=3 (no withdrawal) thirty minutes post-administration of placebo with no change in pupil size. A subsequent rebound partial increase in COWS to 6-8 (mild withdrawal) and SOWS=4-8 (mild withdrawal) occurred until administration of her usual methadone dose, after which SOWS=0 and COWS=1 (no withdrawal for both).

Conclusion & Discussion: We began our pilot expecting that signs and symptoms of opioid withdrawal would consistently worsen during sessions in which patients received placebo (0 mg opioid). However, after receiving either oxycodone or placebo, both participants showed improvement not only in their subjective SOWS scores, but also in objective components of their COWS scores, with a corresponding pupil size decrease for Participant #1. The interventions we used, including turning off the lights, providing water, ice packs and fans, and allowing the patients to lie down, are all free or low-cost and easy to implement, and all greatly contributed to patient comfort and relief. However, nonpharmacological relief was more transient and of smaller magnitude versus pharmacological relief.

While the importance of nonpharmacological therapy for opioid-dependent neonates is established,4 such interventions are not currently the standard of practice for opioid-dependent adults in withdrawal. The ability of nonpharmacological adjuncts to attenuate and even completely suppress opioid withdrawal signs as well as symptoms in these two individuals calls for larger controlled studies on this topic and suggests the importance of implementing adjunctive nonpharmacologic interventions to contribute to the relief of the symptoms and diminution of the signs of opioid withdrawal in opioid-dependent patients of all ages.

References: 1. Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). Journal of psychoactive drugs. 2003;35(2):253-259.
2. Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. The American journal of drug and alcohol abuse. 1987;13(3):293-308.
3. Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. The Lancet. 2020;395(10241):1938-1948.
4. Velez ML, Jordan C, Jansson LM. Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence–based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS. Neurotoxicology and teratology. 2021;88:107032.