Withdrawal can be precipitated by the addition of an opioid antagonist drug into the system while an opioid agonist is still active.

Heroin, for example, is a full opioid agonist that acts on opioid receptors in the brain. If a drug like naloxone, which is an opioid antagonist, is introduced while heroin is still working, precipitated withdrawal can occur.

Precipitated withdrawal can be more intense than typical opioid withdrawal, and it can come on faster.

The best way to manage precipitated withdrawal is to avoid it by not combining agonist and antagonist drugs. If withdrawal is precipitated, it can be handled through supportive care and additional medications to manage the specific symptoms.

More than 2 million Americans struggled with an opioid use disorder in 2016. Opioid withdrawal can be severe and intense for these individuals. It may include both physical flu-like side effects and emotional mood swings and distress. Precipitated withdrawal simply intensifies these effects.

Understanding Precipitated Withdrawal

Precipitated withdrawal occurs when a drug that is considered to be an antagonist essentially “kicks out” an agonist drug.

An opioid agonist works by activating opioid receptors that occur naturally in the brain. When this happens, the way the brain moves dopamine around changes.

Dopamine is one of the pleasure-inducing natural chemical messengers produced by the brain that tells you when to feel happy. When levels of dopamine go up, your mood elevates too. This can create the opioid high.

An opioid antagonist blocks opioid receptors from receiving opioid drugs. It can also remove opioids from the receptors and therefore prevent them from being further activated. This action can cause dopamine levels to drop quickly, and that precipitates withdrawal. 

Withdrawal symptoms can come on quickly when withdrawal is precipitated. They can also be more intense than acute withdrawal, including the following symptoms:

  • Depression
  • Anxiety
  • Irritability
  • Restlessness
  • Dizziness
  • Headache
  • Fever
  • Agitation
  • Heart palpitations
  • Insomnia
  • Nausea, vomiting, stomach cramps, and diarrhea
  • Muscle aches
  • Sensitivity to pain
  • Tremors
  • Memory issues
  • Difficulties thinking clearly
  • Balance and coordination problems
  • Chills and goosebumps
  • High blood pressure
  • Mood swings
  • Tearing
  • Dilated pupils
  • Sweating

Precipitated Withdrawal With Different Drugs

There are three main FDA-approved medications for treating and managing opioid dependence: methadone, buprenorphine, and naltrexone.

Methadone is a full opioid agonist, albeit a long-acting one. Buprenorphine is only a partial agonist. Buprenorphine is often combined with naloxone in the form of Suboxone, Zubsolv, and Bunavail. Naloxone is also an opioid antagonist that is used on its own to reverse an opioid overdose. Naltrexone is an antagonist drug.

Buprenorphine, buprenorphine combination medications, and naltrexone can all precipitate opioid withdrawal if introduced when a full opioid agonist is still active in the bloodstream. Typically, the naloxone component of the buprenorphine/naloxone medications lies dormant unless the drug is misused through injection, and then, it can precipitate withdrawal symptoms.

Naltrexone and naloxone can both be used to maintain sobriety when administered after all opioids are processed out of the body. If another opioid is introduced while taking naltrexone or naloxone, precipitated withdrawal can start. As a result, these medications are often used later in opioid addiction treatment or recovery as maintenance medications to enhance treatment compliance.

Buprenorphine, as a partial opioid agonist, can also precipitate withdrawal if it is started too soon and before a full opioid agonist is completely out of the system. This happens because buprenorphine will replace the full agonist and have a weaker agonist effect. This means the euphoric impact is much lower, and therefore, the brain can experience an imbalance of mood-enhancing brain chemicals.


Handling Precipitated Withdrawal

The National Institute on Drug Abuse (NIDA) publishes that the ideal way to deal with precipitated withdrawal is to keep it from happening in the first place.

You need to be honest about your symptoms, and the last time you used an opioid drug. Starting an opioid substitution or maintenance medication too soon can precipitate withdrawal.

Typically, buprenorphine can safely be introduced after the high burns out, when early withdrawal starts. This is usually within the first six to 12 hours after taking an opioid. Methadone can stay in the system much longer, and you may need to wait longer to use these medications. 

Once precipitated withdrawal has started, medical treatment is needed. Clonidine, lofexidine, nonsteroidal pain medications, and antiemetics can help manage symptoms of precipitated withdrawal. 

In addition to medications for specific physical and psychological withdrawal symptoms, supportive care can help to keep you safe and comfortable. A specialized detox and addiction treatment facility can offer all the necessary care and support for precipitated withdrawal.

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