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The Buprenorphine Effect on Depression

Disclaimer: The FDA has approved buprenorphine (Subutex®) and buprenorphine/naloxone (Suboxone®) to treat opioid dependence. However, neither Suboxone nor Subutex have been approved by the FDA for the treatment of depression or pain. Thus any use of Suboxone and Subutex for pain or depression is considered an offlabel, unapproved use of these medications. The study* Dr. Gracer refers to was conducted in 1995, before the development of Suboxone and FDA approval of both Suboxone and Subutex. Currently, there is no buprenorphine product approved for the treatment of depression.

The purpose of the article was an academic exercise and to help some patients understand why they feel the way they do.

*Journal of Clinical Psychopharmacology.
15(1):49-57, February 1995. Bodkin, J. Alexander MD; Zornberg, Gwen L. MD; Lukas, Scott E. PhD; Cole, Jonathan O. MD

by Richard Gracer, MD
Patients with opiate addiction, who are treated with buprenorphine, often ask why the buprenorphine eliminates their depression as well. Many of these people have never felt better in their lives since starting this drug.

Buprenorphine is extremely effective for the treatment of opiate addiction, effectively stopping withdrawal and cravings. This is because of its actions as a partial Mu receptor agonist. Over time this partial Mu agonist action of buprenorphine allows the Mu receptor to move back towards normalcy.

There is another important opiate receptor in the brain called the kappa receptor. Much of the long lasting Post Acute Withdrawal syndrome felt by the addicted patient is due to the kappa overactivity that is associated with opiate withdrawal causing dysphoria, body aches, anxiety, and depression. This can last for months or even years and is an important cause for relapse. I believe that kappa activation may be an important cause of depression in many persons with substance abuse problems as well as in the general population, even without the extra stimulation of opiate withdrawal.

Buprenorphine is a potent, long acting kappa blocker. Opiates are not as specific in their kappa blocking actions as buprenorphine and most are short acting, so the patients that get benefit from this opiate action often must use frequent and ever higher doses of their opiate to get effective consistent blocking of kappa. This dose increase causes the Mu receptors to become less sensitive to opiates and therefore the patient requires higher and higher doses to get pain relief and stay out of withdrawal. This is the vicious cycle we so often see.

Many of these patients started taking Vicodin, Norco, or other opiate medication for legitimate pain, usually prescribed by their own physician. They find out very quickly that their depression, anxiety and lack of energy also disappears, often for the first time in their lives. I believe that this is due to kappa blocking. The usual cycle then results in addiction. These folks have often tried SSRI’s and other antidepressants in the past without success. Buprenorphine often makes them feel wonderful. The Mu receptors get re-regulated in the short to medium term, but the kappa is still a problem. Most of these patients did not have a normal kappa system prior to opiates.

Many patients can taper their buprenorphine dose down to as low as 0.5 to 1 mg daily and feel fine. I believe that these folks are taking the drug as an antidepressant and are not addicted to opiates anymore than other depressed patients are addicted to Prozac. They need to continue the medication to treat their depression, I think that many of these folks may have bipolar chemistry as well.

We see this all the time in addicted patients. It runs through families genetically like a hot knife through butter. All physicians should screen their patients for a family history of substance abuse and psychiatric illness all the way back to grandparents, prior to medicating a patient, even for acute pain. Patients should of course be treated for their pain and monitored for the usual things we see in addicted patients so that corrective/ preventative action may be taken early.

There has been a study using buprenorphine in a small number of patients with depression who had not responded to other antidepressants. Of the ten patients in the study, three had side effects and could not use the medication. Four of the others had complete recovery, two had significant improvement and one got worse. This clearly shows that buprenorphine has potential as an antidepressant and should be studied further. It certainly supports the observations of so many of physicians either treating patients or of the patients themselves that buprenorphine is an effective antidepressant. The exact dosage and patient types that would best be treated in this way needs to be worked out.

Dr. Richard Gracer is the founder and director of Gracer Medical Group in California. He is also the author of the much anticipated book, “A New Prescription For Addiction” coming out late April/May 2007. Advance copies can be purchased at Amazon now.

The much anticipated HBO series "Addiction"
Addiction bannerwill début March 15th 2007. It is said to be a groundbreaking look at the science of addiction and will likely dispel many of the myths that plague addiction medicine. The series will initially be offered during a free HBO preview weekend from Thursday, March 15 to Sunday, March 18 on participating cable and satellite systems.

Why Is this Project Different?
Countless television shows, both fictional and real, have captured the seemingly hopeless downward spiral of the drug addict or alcoholic. But, they have failed to explain to the public:

  • What addiction really is (a brain disease);
  • What causes it (a variety of genetic and psychosocial factors); and
  • How to get the best available treatment (by seeking out evidence-based medical and behavioral treatments).

A coalition of advocacy organizations have teamed up to make this an event. See for more information.

Before and after the HBO program, there will be discussion about the show on the NAABT discussion board. All are welcome to participate.

NAABT Discussion Forum.

The NAABT discussion forum, continues to evolve with over 2000 members. This online peer support forum works in addition to traditional counseling. It serves to fill in the gaps and answer questions between visits and allow the patient to anonymously converse with others with similar experiences from anywhere in the world. We believe this leads to lower anxiety about starting a new treatment and helps create realistic patient expectations.

A study by Ritu Agarwal of the University of Maryland examined the impact of online support forums on people wishing to quit smoking. Of the 411 participants 62% successfully quit with the use of the forum, compared with the National average success rate of <25%, according to the National Lung Association. The researcher noted that by being able to choose who the participant receives support from, they are better able to match themselves with people more likely to understand their particular situation. She also noted that the more time spent on the forum the greater the likelihood of success. The anonymous forum helps decrease embarrassment, and anxiety and allows the participant to discontinue support at any time.

The forum format in the study is almost exactly the same format as the one NAABT uses. The significance of this anonymous 24/7 peer support is just now being recognized as a valuable part of treatment. With more than half of the households in the US now with broadband internet, this option is becoming more and more practical.

In the near future counseling via the internet will become a more accepted option. It will allow patients to better match their individual needs with a counselor with those specific specialties and not limit the patients to their geographic area of travel. is leading the way with internet counseling. They have the technology in place now and have made a substantial commitment to making this a viable treatment option. They provide a higher level of care than peer based support forums and fill the gap for those with greater needs.

We need your help. Although the NAABT Patient/Physician Matching System has helped match over 2,000 patients to certified providers, it has the capacity to match several times that amount. Currently there are over 950 participating physicians. We need to make more patients aware of this resource. You can help by directing patients to this resource, or if you have a website, adding the shortcut banner as a convenience to your visitors:

Buprenorphine Treatment Banner

Learn how to add this banner
or other designs to your website.

The Physician Locator (Doctor/Patient button) sorts physicians by distance in geographic proximity, regardless of city,
town, county, or state borders. Click here to try it for yourself.

NAABT Patient/Physician Matching System We continue to improve the matching system based on your feedback. A new Frequently Asked Questions page has been added to explain some of the latest improvements.

SAMHSA If you are a certified physician please be sure your information is correct on the locator. Please check for spelling and correct phone number. If you know of a colleague who is on the list but should not be due to no longer practicing, please advise.
Please note: If you have multiple practice locations, you can now add them.1-866-287-2728

PCSS releases clinical guidelines for buprenorphine treatment concerning, Acute pain, liver function testing, Billing, Pregnancy, Transitions from methadone, and Management of psychiatric medications.
PCSS Resources:

Disclosure:NAABT, Inc. has accepted funding from Reckitt Benckiser (Richmond, VA, pharmaceutical company that manufactures buprenorphine products) in the form of an “Unrestricted Educational Grant.” The grant is “unrestricted” so that there are no “strings” attached. NAABT, Inc. has complete control over how the funds are used, there are no restrictions on the content or mission of this site, and Reckitt has no control over the content of the site or NAABT’s activities. Reckitt is currently the only FDA approved maker of a buprenorphinebased product for addiction. NAABT, Inc. is not affiliated with Reckitt Benckiser. Click here to learn more about NAABT.

Click here to learn more about NAABT.

The National Alliance of Advocates for Buprenorphine Treatment is a 501(c)(3) non-profit organization formed to help people, in need of treatment, find treatment providers who are willing and able to treat opioid dependency in the privacy of a doctor’s office. Our website offers answers to frequently asked questions, a glossary, actual patient experiences, a discussion board, information on the history and treatments of opioid addiction, current news on the subject and more.

This newsletter is provided to keep you informed on matters relating to Buprenorphine Treatment. Please feel free to contact us at with feedback, suggestions, or perhaps you would like to contribute a story. Also feel free to photocopy or print as many as these newsletters as you wish for distribution.

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