What Is Clonidine? How Does Clonidine Work?

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April 19, 2022

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What is Clonidine?

Currently, the World Health Organization (WHO) and the U.S. Food and Drug Administration (FDA) have approved three medications for addiction treatment (MAT) for opioid use disorder (OUD): methadone, buprenorphine, and naltrexone. These have improved outcomes for thousands of people who need help overcoming opioid misuse and use disorder.

Since opioid withdrawal symptoms are both physically and psychologically painful, medical professionals have considered several other methods for managing this experience. Clonidine is one medication that can treat the uncomfortable symptoms of opioid withdrawal.

Clonidine was developed to manage hypertension (high blood pressure) and severe cancer pain, but since its FDA approval, the prescription drug has been found to have several other important uses, including in opioid use disorder treatment.[1] In particular, for people who need help during opioid withdrawal but choose not to use buprenorphine or methadone, it can alleviate many of the symptoms of opioid withdrawal. 

In addition, clonidine is also sometimes used off-label for reduction of anxiety, insomnia, and hyperarousal seen with disorders like post-traumatic stress disorder (PTSD). Interestingly, any of these are also the same symptoms people have when they are coming off of  opioids, alcohol, and benzodiazepines. Although this is an “off-label” prescription use for clonidine, many people benefit from taking this medication to ease withdrawal as they begin other MAT, like Suboxone or when they are transitioning off Suboxone or methadone after long-term use.

Clonidine for MAT

Clonidine has been used off-label for over 25 years to relieve the symptoms of opioid withdrawal syndrome, but it is typically prescribed to ease acute withdrawal rather than as a long-term maintenance medication.[2]

Clonidine is not an opioid agonist, so it does not bind to the opioid receptors in the brain like methadone or buprenorphine. However, the medication can ease some of the more intense, acute withdrawal symptoms, and it can also reduce cravings for opioids.

When you begin MAT for opioid addiction, the last dose of illicit opioids needs to metabolize out of your body before you begin maintenance treatment. Typically, withdrawal symptoms begin within a few hours of the last dose, but it can take about a day of working with your physician to get the right buprenorphine/Suboxone dose for you. During this time, you may receive clonidine to ease withdrawal symptoms.

Clonidine may also be prescribed as a bridge between tapering off Suboxone or methadone and initiating naltrexone. Since naltrexone is a long-lasting opioid antagonist, the first injection of this medication cannot be given until the individual has fully tapered off buprenorphine or methadone for 7 to 14 days. Otherwise, naltrexone will trigger withdrawal symptoms.

However, some withdrawal symptoms may linger after tapering, and clonidine can ease these. Or, if naltrexone does trigger withdrawal, clonidine can ease this experience, too.

Unlike MAT, however, clonidine is not an effective long-term treatment for opioid use disorder. Its effects on cravings and as a relapse-prevention agent are far inferior to medications like buprenorphine, methadone, and naltrexone, studies show.

How does Clonidine work?

Clonidine is categorized as an antihypertensive medication. The medication excites pathways in the central nervous system that inhibit cardiovascular neurons, relaxing some of these muscles. The medication also reduces sympathetic outflow from the CNS, which causes the decrease of arterial blood pressure.

These effects can also ease the experiences of anxiety and pain. One theory of clonidine’s mechanism of action involves easing pain signals from the spinal cord to the higher centers of the brain by releasing norepinephrine to produce analgesia and relaxation.

By increasing analgesia, clonidine is sometimes combined with anesthesia to increase the duration of pain-relieving and relaxing properties, including for opioids. Clonidine is believed to enhance neuraxial opioids, which can reduce the postoperative painkiller dose by up to 60%.

Many of the uncomfortable and painful symptoms experienced during opioid withdrawal result from a hyperactive sympathetic nervous system. Clonidine helps to reduce this hyperactivity, thereby minimizing various withdrawal symptoms, including hot flashes, sweating, muscle aches, runny nose, anxiety, and irritability.

Clonidine comes in three forms: a tablet, an injection, and a transdermal patch. The transdermal extended-release patch seems to be most effective for alleviating opioid withdrawal symptoms.

Side Effects of Clonidine

Although clonidine is a beneficial medication, it can cause some side effects.[3] Common side effects include the following:

  • Abdominal pain, nausea, constipation, and diarrhea
  • Headaches
  • Hypotension, or low blood pressure
  • Dizziness
  • Fatigue and sedation
  • Emotional instability
  • Xerostomia, or dry mouth
  • Sexual dysfunction or decreased sexual activity and arousal

There are other rare, but serious, side effects. Discuss these with your doctor if you are concerned or if you have any underlying conditions that might contribute to them. These rare symptoms include the following:

  • Depression and agitation
  • Hypersensitivity 
  • Angioedema, in which small blood vessels leak fluid into surrounding tissues which causes swelling
  • Bradycardia, or a slower than normal heart rate
  • Severe hypotension, which can prevent blood from flowing normally and lead to fainting (syncope)
  • Congestive heart failure
  • Thrombocytopenia, or low platelet count in the blood, which can affect clotting and cause excessive bleeding

Allergic reactions to clonidine are also rare, but they can cause serious problems. If you develop hives, a rash, swelling in the face, mouth, or throat, trouble breathing or swallowing, or serious itching, call 911 immediately.

Short-term use of clonidine should not lead to too many side effects or adverse reactions, but people who take this medication on a long-term basis at high doses might develop a physical dependence, which can lead to withdrawal symptoms if they suddenly stop taking it.[4]

The main symptom is rebound hypertension, or high blood pressure. For people taking clonidine off-label, this can feel like a pounding heart, fatigue, insomnia, or anxiety.

These are other withdrawal symptoms:

  • Tachycardia, or rapid heart rate
  • Headache
  • Nausea
  • Flushing or warm feeling in the face or skin
  • Tightness in the chest
  • Tremors
  • Lightheadedness

How Do You Get Clonidine?

Clonidine is only available with a prescription, even if you are given it for an off-label use. Health insurance, including Medicare, will cover clonidine prescriptions, but off-label use can be difficult to navigate.[5]

Fortunately, since clonidine is a generic drug, it does not cost much without insurance.[6] Oral tablets cost, on average, $10.31 for eight tablets at 0.1 mg and $14.22 for 30 tablets at 0.3 mg. The extended-release transdermal film at 0.1 mg (which lasts for 24 hours) can cost $62.55 for four films, but this is four days of doses, which can be enough to ease acute withdrawal from opioids.

There are also patient rebate programs and coupons available that can help you save money on clonidine. Ask your physician or pharmacy about these options.

Learn more

Bicycle Health is dedicated to helping people get off and stay off opioids. To learn more about the success rates and safety of Bicycle Health’s telemedicine addiction treatment in comparison to other common treatment options, call us at (844) 943-2514 or schedule an appointment here.

Picture courtesy of HalGatewood.com on Unsplash.

Medically Reviewed By Claire Wilcox, MD

Claire Wilcox, MD, is a general and addiction psychiatrist in private practice and an associate professor of translational neuroscience at the Mind Research Network in New Mexico; and has completed an addictions fellowship, psychiatry residency, and internal medicine residency. Having done extensive research in the area, she is an expert in the neuroscience of substance use disorders. Although she is interested in several topics in medicine and psychiatry, with a particular focus on substance use disorders, obesity, eating disorders, and chronic pain, her primary career goal is to help promote recovery and wellbeing for people with a range of mental health challenges.

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  1. Clonidine. DrugBank.com. https://go.drugbank.com/drugs/DB00575. February 2022. Accessed February 2022.
  2. Clonidine. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK459124/. August 2021. Accessed February 2022.
  3. Clonidine. Medline Plus. https://medlineplus.gov/druginfo/meds/a682243.html. February 2022. Accessed February 2022.
  4. Highlights of Prescribing Information: Kapvay. Access Data FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022331s014lbl.pdf. Accessed February 2022.
  5. Does Medicare Cover Clonidine or Catapres? Medicare Advantage. https://www.medicareadvantage.com/rx-coverage/clonidine#:~:text=Yes!,Part%20D%20plans%20cover%20Clonidine. Accessed February 2022.
  6. Clonidine Prices, Coupons and Patient Assistance Programs. Drugs.com. https://www.drugs.com/price-guide/clonidine. Accessed February 2022.

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