Dangers of Long-Term Suboxone Treatment

Treatment of opiate addiction, or “opioid use disorder” (OUD), is a complex and comprehensive process that involves assessment, diagnosis, medication, psychosocial support, planning a treatment program, monitoring and numerous other social services. The U.S. Food and Drug Administration (FDA) has approved three medications for the treatment of opioid use disorder: methadone, naltrexone, and buprenorphine.

The three medications are, respectively, agonists, antagonists, and partial agonists drugs used to treat addiction to opiates such as the illegal drug heroin, as well as prescription drugs such as oxycodone and hydrocodone prescribed for the treatment of pain.

MEDICATION-ASSISTED TREATMENT

Medication-Assisted Treatment (MAT) is an approach using FDA-approved medications, along with psychosocial therapy, to help address the growing problem in America of both illicit and prescription-drug opiate dependence and addiction.

• Methadone is a synthetic opiate, an agonist, that makes withdrawal symptoms less severe and can, with higher doses, block the effects of opiate-containing drugs and heroin. Methadone can only be dispensed at an outpatient treatment program (OTP) that is certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) and registered with the Drug Enforcement Agency (DEA), or to a person hospitalized in an opiate emergency.
• Naltrexone is an antagonist. Non-narcotic and non-addictive, naltrexone blocks the opiate receptors in the body, so they cannot be activated. While on naltrexone, a person will not be able to feel the effects of any opiate drug they take. Naltrexone is an injectable, long-lasting drug approved to prevent relapse in those with opioid use disorder after they have been through detoxification from opiates and have been opiate-free for a period of 7-10 days.
• Buprenorphine is a partial agonist that helps quell withdrawal symptoms. While buprenorphine can create some of the effects and side effects of opiates, such as euphoria and respiratory depression, they are generally milder than the effects of full-on agonist drugs like heroin and methadone. Buprenorphine, approved by the FDA in 2002, can only be distributed by specially trained physicians in intensive outpatient and inpatient treatment centers, and prescribed by specially trained doctors in office settings, with prescriptions filled at pharmacies. Doctors also must sign a waiver granted by the DEA to prescribe buprenorphine.

SUBOXONE

Suboxone is the brand name of a combination drug containing buprenorphine and naloxone. The latter is a drug used to overcome the effects of an opiate overdose. Suboxone is placed under the tongue and allowed to dissolve. Taking the medication this way reduces naloxone’s effect. However, if a person injects Suboxone, naloxone gets into the bloodstream and blocks the positive effects of buprenorphine, causing the person to go into opiate withdrawal.

HOW SUBOXONE IS USED IN TREATMENT

Ideally, Suboxone is used for the short-term treatment of opiate addiction and dependence, typically during the initial detoxification (detox) phase. Use of the medication may continue past detox, but generally for only a short period. Determination is made by the patient’s treatment team after a thorough review of how the individual has progressed through detox, whether there are other indications that MAT should continue, and other considerations unique to the patient and his or her diagnosis.

Once the suboxone detox has been completed, the patient begins the second phase of treatment. That’s because detox alone is not enough to prevent relapse to opiates. Ongoing counseling, introduction to support groups and other techniques provide a better foundation for living drug-free. Treatment consists of behavioral therapies, social support, and other approaches. The goal is to help the person learn how to live a life in recovery from opiates. As such, a significant portion of the treatment plan consists of education about addiction and recovery and interaction in healthy lifestyle pursuits. Also, beginning in this phase is an introduction to and participation in self-help support groups, a resource available to all persons in recovery and highly recommended for long-term sobriety.

WHY NOT TAKE SUBOXONE LONG-TERM?

If Suboxone blocks withdrawal and only creates mild effects of euphoria and/or respiratory depression, what’s wrong with taking the medication long-term? As previously stated, the goal of treatment for opiate addiction is not to substitute one drug, albeit an FDA-approved Medication-Assisted Treatment drug, for an opiate. The goal is to learn to overcome dependence on substances of abuse.

There are also numerous dangers associated with long-term use of Suboxone. Some of these can be life-threatening.

Overdose

Severe negative side effects include overdose, resulting in unconsciousness, severe respiratory depression, and death. This is especially risky for those who inject Suboxone and take tranquilizers or sedatives or drink alcohol. Life-threatening situations can develop from taking excessive amounts of oral Suboxone in combination with other opiate medications, certain antidepressants, sedatives, tranquilizers or alcohol.

Hepatitis

While on long-term Suboxone treatment, some people have developed hepatitis, an inflammation of the liver. Symptoms include jaundice, nausea, stomach pain, lack of appetite, dark urine and bowel movements of a light color.

Allergic Reaction

Cases of hypersensitivity (allergic reaction) to buprenorphine and naloxone have been reported both during and after clinical trials of Suboxone. These include reports of cases of anaphylactic shock, angioneurotic edema and bronchospasm. Common symptoms of an allergic reaction include severe itching, hives, and rashes.

Other Adverse Reactions to Long-term Suboxone Use

Long-term use of Suboxone has resulted in some additional adverse reactions, according to the full prescribing information issued by the drug manufacturer. These include:

• Adrenal Insufficiency
• Androgen Deficiency
• Anaphylaxis
• Serotonin Syndrome

Keep in mind that the decision to taper off from Suboxone treatment is one that should only occur as part of a comprehensive treatment plan. The treatment team will make the decision when the time is right for the patient to receive a slightly lower dose while also remaining cognizant of minimizing withdrawal cravings. Concerns about opiate relapse should be discussed with the doctor and the treatment team.

For the 12-month period ending January 2018, the Centers for Disease Control and Prevention (CDC) estimates about 70,000 drug overdose deaths reported in the United States, while the predicted number of deaths exceeds 71,500. Opiates, including fentanyl, heroin, oxycodone, hydrocodone, and other synthetic opiates, contributed more than 49,000 to the drug overdose deaths. Fentanyl alone accounted for 30,000 drug overdose deaths, 22 times the rate of deaths from those drugs in 2002.

Suboxone’s Effects on the Brain

Addiction is a chronic, relapsing brain disease characterized by drug use and drug-seeking behaviors, despite harmful consequences. Long-term drug use changes the brain in terms of structure and how it works, resulting in long-lasting changes that may precipitate or continue self-destructive and harmful behaviors. Following detox for opiate drug dependence and addiction, the brain is still in deficit mode as a result of chronic drug use.

Despite its legitimate effectiveness in short-term treatment for OUDs, Suboxone is not recommended for long-term maintenance. There are numerous studies examining the effects of Suboxone used long after detox and withdrawal from opiates showing the negative repercussions of continuing use. Such effects on the brain include:

• Anxiety
• Confusion
• Decreased coordination
• Depression
• Disorientation
• The feeling of being lost
• Suicidal thoughts

A study in PLOS One found a “significantly flat affect” in long-term Suboxone patients, noting they had less self-awareness of being happy, sad and anxious, compared to the general population or Alcoholics Anonymous (AA) groups.

Another study found that, despite the lack of any currently available FDA-approved opiate maintenance compound, the combination of buprenorphine/naloxone in long-term maintenance should be used with caution, “due to a significant alteration in mood and emotion.” The researchers expressed concern due to the multitude of evidence of severe withdrawal (even with tapering Suboxone dosage, still 40 times the potency of morphine) from low-dose buprenorphine (with or without naloxone).

The researchers also found long-term flat effect and other unwanted side effects that included diversion of Suboxone and suicide attempts among those on Suboxone for long-term maintenance (average of 1.66 years). They recommended genetic testing to potentially discover reward circuitry gene polymorphisms, and especially those that may be related to dopaminergic pathways and opiate receptors as a means to improve treatment success and outcomes. 

Sources:

Centers for Disease Control and Prevention. “National Center for Health Statistics.” “NVSS Vital Statistics Rapid Release.” “Provisional Drug Overdose Death Counts.” Retrieved from https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm

Journal of Addiction Research and Therapy. “Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents. Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?” Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318568/

Molecular Neurobiology. “Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?” Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682495/

National Institute on Drug Abuse. “The Science of Drug Abuse and Addiction: The Basics.” “What is drug addiction?” Retrieved from https://www.drugabuse.gov/publications/media-guide/science-drug-abuse-addiction-basics

PLoS One. “Long Term Suboxone™ Emotional Reactivity As Measured by Automatic Detection in Speech.” Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706486/