Precipitated withdrawal refers to withdrawal symptoms triggered by medication-assisted treatment (MAT) drugs used in treating substance abuse rather than the lack of the abused substance itself. Medications like Suboxone, Subutex and Naltrexone, common in MAT, can cause these symptoms. The issue often arises with drugs such as buprenorphine, which has a high affinity for opioid receptors in the brain. When administered to someone addicted to heroin, buprenorphine displaces heroin molecules from these receptors, leading to a lesser opioid effect and precipitating withdrawal symptoms due to the receptors being suddenly deprived of the expected opioid effect. This can result in a range of symptoms from muscle aches, fever and insomnia to more severe effects like depression and suicidal thoughts, especially in individuals with a long-term heroin dependency and significant physical dependence. Despite buprenorphine’s intention to mitigate withdrawal symptoms in opioid-dependent individuals, its partial agonist nature can paradoxically trigger withdrawal in those with high heroin tolerance.

Precipitated withdrawal occurs when the normal activation of opioid receptors in the brain and spinal cord by opioid agonists (keys), such as morphine, fentanyl and heroin, is interrupted by opioid antagonists like naloxone and naltrexone, which block these receptors without activating them. This blocking action can cause sudden withdrawal symptoms in individuals physically dependent on opioids. Buprenorphine, a partial opioid agonist, similarly occupies these receptors but only partially activates them, which can also lead to precipitated withdrawal in opioid-dependent individuals if not administered carefully. Contrary to some beliefs, the naloxone in buprenorphine/naloxone combinations, used to prevent misuse, does not cause precipitated withdrawal when taken as directed because it remains inactive when administered sublingually.

Drugs that Cause Precipitated Withdrawal

Various drugs can induce precipitated withdrawal (POW) by interacting with the mu-opioid receptors, which are typically utilised by opioids, thus blocking the opioids’ access and leading to POW symptoms. Drugs like Buprenorphine, a partial opioid agonist found in medication-assisted therapy for opioid use, along with Butorphanol and Nalbuphine, used for pain management, can cause POW due to their partial agonist nature. Opioid antagonists such as Naloxone (Narcan), a reversal drug for opioid overdose and Naltrexone (Vivitrol), used for treating alcohol and opioid addiction, directly displace opioids from the mu receptors, triggering POW. Similarly, Alvimopan (Entereg), used post-surgery for bowel issues and opioid-induced constipation treatments like Naloxegol (Movantik), Naldemidine (Symproic) and Methylnaltrexone (Relistor) are opioid antagonists that can lead to POW, especially in individuals with compromised blood-brain barriers. Further to that certain drugs like Rifampin, Phenytoin, St. John’s Wort, Phenobarbital and Carbamazepine can expedite the body’s clearance of opioids, further contributing to withdrawal symptoms, illustrating the complex interactions between various medications and opioid receptors in the body.

MAT Can Unintentionally Trigger Withdrawal, Complicating Recovery

What are the common symptoms of precipitated withdrawal associated with medication-assisted treatment medications like buprenorphine or Naltrexone? Get help from qualified counsellors.

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