Naltrexone is a medication primarily prescribed to assist individuals in recovery from Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD). It functions as an opioid antagonist, blocking the effects of opioid substances on the brain’s receptors. This action helps reduce cravings for alcohol and blocks the euphoric effects of opioids. Like most pharmacologic treatments, Naltrexone can be associated with various side effects. A common concern for patients starting the drug is the potential for developing headaches.
Headaches as a Known Side Effect
Headache is a recognized and frequently reported side effect for patients taking Naltrexone, regardless of whether they use the daily oral tablet or the extended-release injectable formulation. Clinical trial data consistently show that headaches are one of the more common adverse events experienced during treatment. In studies involving patients with Opioid Use Disorder, over 10% reported a headache.
For those taking the medication for Alcohol Use Disorder, new-onset headaches occurred in approximately 6.6% of patients. These headaches are generally mild to moderate in severity and often temporary. Patients frequently find that the headaches decrease in intensity and frequency as the body adapts to the drug over the first few days or weeks of treatment. Experiencing a headache upon initiation of Naltrexone is a typical response and is part of the adjustment phase.
Biological Basis of Naltrexone-Induced Headaches
The reason Naltrexone can trigger headaches is directly related to its function as an opioid receptor antagonist. The medication works by blocking the body’s opioid receptors, specifically the mu-opioid receptor. This action temporarily disrupts the body’s natural opioid system, which relies on internally produced compounds called endorphins.
Endorphins are naturally occurring neurotransmitters that regulate pain, mood, and stress response, and they also play a role in regulating blood vessel tone in the brain. By blocking the receptors where these natural opioids normally bind, Naltrexone causes a sudden shift in this delicate internal balance. This temporary imbalance in neurotransmitter signaling and vascular regulation is thought to contribute to the development of tension-type or vascular headaches.
For some individuals, the sudden blockage of opioid receptors may mimic mild symptoms associated with opioid withdrawal, even if they have been opioid-free before starting the drug. Headaches are a known symptom of withdrawal, and this reaction is essentially the nervous system adjusting to a new level of endorphin activity. Furthermore, some research suggests Naltrexone may act on the Toll-Like Receptor 4 (TLR4) pathway, which is involved in inflammation and pain signaling.
Managing Headaches and Recognizing Warning Signs
Management Strategies
For most patients, Naltrexone-induced headaches are a transient side effect. Ensuring adequate hydration and maintaining a regular sleep schedule during the initial weeks of treatment is beneficial. Patients may find relief through over-the-counter pain relievers, such as Ibuprofen or Acetaminophen, but they must confirm the use of any non-prescription medication with their prescribing physician.
If taking the oral tablet, adjusting the time of day the medication is taken may help minimize the headache’s impact on daily activity. These mild side effects typically resolve on their own as the body acclimates to the medication, often within the first two weeks. Tracking the frequency and severity of the headaches can help the healthcare provider determine if the side effect is improving or requires further intervention.
Never stop taking Naltrexone without consulting the prescribing physician, even if the headaches are bothersome. Discontinuing the medication abruptly can negatively impact the success of the treatment plan for Alcohol Use Disorder or Opioid Use Disorder. If the headaches persist, worsen significantly, or interfere with quality of life, a healthcare provider can discuss options such as dose adjustment or alternative management strategies.
Recognizing Warning Signs
While mild headaches are common, certain symptoms must be immediately reported to a medical professional as they may signal a more serious underlying issue. These “red flag” symptoms include:
- A sudden, extremely severe headache described as the “worst headache of your life” or a “thunderclap” headache.
- Fever.
- A stiff neck.
- Confusion.
- Vision changes.
- Persistent vomiting.
A severe headache accompanied by any of these symptoms warrants urgent medical attention.