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.
www.gracermedicalgroup.com 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.