Dunn 2023: defining precipitated opioid withdrawal with a naloxone challenge

What they tested

Precipitated withdrawal is withdrawal set off suddenly by a drug that blocks opioid receptors. Ordinary withdrawal is well described, but precipitated withdrawal had no agreed working definition.

People with opioid use disorder who were maintained on morphine received 0.4 mg of naloxone by injection into a muscle. They rated their symptoms on the Subjective Opiate Withdrawal Scale (SOWS) and on visual analog scales for bad effects and feeling sick, while observers scored them on the Clinical Opiate Withdrawal Scale (COWS).

What they found

Within 60 minutes, 89% of people reported their peak SOWS ratings and 90% reached their peak COWS scores as rated by observers.

Some signs stood out as specific to precipitated withdrawal: teary eyes, yawning, runny nose, sweating and hot flashes reported by participants, and changes in pupil size and runny nose or teary eyes seen by observers.

Participants judged a rise of 10 points on the SOWS (15% of the maximum possible effect, or MPE) and 6 points on the COWS (12% MPE) as a meaningful step up in withdrawal severity.

Limits

• Withdrawal was set off with naloxone in people on morphine, not with naltrexone or buprenorphine in everyday treatment.
• Everyone was maintained on morphine, so it doesn't show how timing or severity compare in people using fentanyl or methadone.
• The authors present it as a method to begin studying precipitated withdrawal, not a final definition.

What it means if you're considering naltrexone

For someone on naltrexone, the main lesson is how fast this kind of withdrawal can come on: in this study 89% of people reported their worst symptoms within 60 minutes of the blocker. It also gives clinicians and researchers a shared yardstick for what counts as precipitated withdrawal.