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Is buprenorphine an antidepressant?

Can Suboxone treat both opiate addiction and depression at the same time?  Dr. Burson says, “No. Buprenorphine is not an antidepressant”.  But should your Suboxone doctor consider using this opioid to treat the disease of depression? Maybe.  Read more about the potential of buprenoprhine as an antidepressant during opiate withdrawal here.

What is the disease of depression?

When doctors talk about the disease of depression, we aren’t speaking of a bad feeling that we all get when having a terrible day. Doctors consult a set of diagnostic criteria that describe a situation of chronically low mood, significant enough to cause considerable suffering. In patients with major depression, we see feelings of low self-worth, hopelessness, and even suicidal thoughts. People with the disease of depression don’t feel pleasure from previously pleasurable activities. We believe this kind of depression is caused by an imbalance of brain chemicals. In the past, scientists thought that the main chemicals affecting mood are serotonin and norepinephrine, and our presently available antidepressants work by adjusting these brain chemicals.

But over the years, it’s gotten more complicated. As science evolves, we’ve begun to see that other brain chemicals affect mood. For example, estrogen and testosterone, the sex hormones, affect mood.  Also, the stress hormones like cortisol play a role in the control of mood, and also may be a factor in the development of addiction.

Can opioids affect mood?

The research on mood and addiction overlap.  Addiction and the brain are interrelated, as are mood disorders and the brain…suggesting future discoveries about how mood disorders and addictions are related. Researchers know that we make our own opioids, called endorphins, which affect mood. At present, we don’t have a way to measure these endorphins, but some scientists believe it’s possible that some people are born with low levels of endorphins. When they use opioids, perhaps they feel “normal.” Without opioids, they may feel chronically low in mood. Perhaps opioids help these unfortunate people to feel like people born with adequate endorphins. This is an exciting area of research, which may help us understand why some people are much more susceptible to addiction than others.

People who have become addicted to opioids experience withdrawal when they don’t have access to their drug of choice. Besides the physical symptoms, which can be quite severe, many addicts also feel depressed and anxious. When they use an opioid, those bad feelings go away, along with the physical symptoms. So opioids elevate a depressed mood, but the depressed mood was caused by addiction to opioids in the first place. This is the official answer to the question of why some people feel less depressed when taking Suboxone. But it’s probably not so simple.  And to find Suboxone doctors taking patients, you’ll need to look at the SAMHSA listing for buprenorphine physicians or check out the Suboxone manufacturer’s website for more information.

Is buprenorphine / Suboxone an antidepressant?

No. Strictly speaking, Suboxone, which is the brand name of the generic drug buprenorphine, is not an antidepressant.

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However, Suboxone is an opioid. All opioids, by stimulating opioid receptors, create feelings of expansive well-being, and even euphoria. This is the “high” that some people become addicted to. If someone is in a foul mood, using an opioid usually produces a much better mood. Suboxone, since it’s only a partial opioid, causes less euphoria, but still can cause this good feeling.  Doctors further prescribe buprenorphine sublingual tablets during opiate withdrawal or for opiate addiction maintenance programs, as its effects are relatively mild and supportive of a better lifestyle.

Discussion

Should we consider treating depression with opioids?

Leave a Reply

22 Responses to “Is buprenorphine an antidepressant?
Jason
10:27 am January 19th, 2011

Hi Dr. Burson,

I stumbled across your article in my random web surfing this evening and after reading it, I feel compelled to offer a different perspective on the topic. I disagree with your seemingly simplistic appraisal of buprenorphine as an antidepressant, as well as the neurochemical explanation of depression. If by using such a term you mean an FDA approved treatment for depression, then it does not meet this criteria. I would like to say that the last paragraph sounded much more enlightened and sympathetic. However, there are several very important points that you neglected to mention. Perhaps being an addiction specialist, you (understandably) focus on the negative implications of opiate use. However, buprenorphine is substantially different pharmacologically speaking than other opiates (of clinical use or abuse). You are obviously aware of it being a partial agonist at the u-opiate receptor, as are most people. It also has some complex effects which most agree include kappa-opiate receptor antagonism, and nociceptin/orphanin partial agonism. Also, it has an active metabolite (norbuprenorphine) with its own pharmacology.

There is a massive amount of information in the scientific literature regarding the kappa system and stress, depression, anxiety and dysphoria. Perhaps slightly more controversial, there is also accumulating evidence of a mood regulating, anxiolytic and some anti-depressant effects of u-receptor agonists. There are studies correlating genetic polymorphisms in opiate function with mood disorders as well. In Bup’s case, its partial agonism at u-receptor, coupled with kappa antagonism, means a reduced response to stress and anxiety(from kappa) and some remediation of anhedonia (by u-receptor). There has even been studies of Bup in treating treatment-resistant depression.

Even some depression experts fail to make the distinction between positive affect and negative affect. Most available antidepressants help reduce negative affect (worry, ruminations, sad mood) but are not so good at improving lack of positive affect (motivation, enjoyment/pleasure). Also the clinical efficacy in general of FDA approved antidepressants is pitiful (Meta analyses and the STAR D trials showed low response and remission rates in ideal clinical settings, much less real world settings).

I think that if a patient facing treatment-resistant depression wishes to try Bup ‘off label’ or for ‘opiate dependence’, they should be allowed such an option.

Now I know what you might be thinking. Oh, they are just getting high and feeling ‘euphoric’. Well many of these people are taking a half a milligram a day of Bup, where the typical doses for opiate-dependent persons is generally much higher.

If you question any particular assertions I have made, feel free to let me know. I would be glad to email you the PDF journal articles that are the sources for my above claims.

Thanks and rock on Dr. Burson

Jana Burson M.D.
9:53 pm January 20th, 2011

Thank you for writing! I admire your education about the pharmacology of opioids. And the more research that’s done, the more complex the information gets! As you likely know, scientists are finding that there are more types of opioid receptors than the mu, delta, and kappa that were originally described, with even more complicated effects on the body, when stimulated.

However, I stand by my position that there’s not enough information – at present – to justify starting patients on buprenorphine as an off-label treatment for depression. What if, for example, buprenorphine does treat depression – but only for a year or so. What then? We have a patient who’s depressed and addicted to opioids.

Jason
12:26 pm January 27th, 2011

Thanks for the reply Dr Burson, I appreciate it! I agree with you regarding the complexity of our neurochemistry, and the existence of other opiate receptor types or subtypes. I did briefly mention the nociceptin/orphanin FQ with regards to Bup’s pharmacology.

I respect your difference of opinion, but if its ok I would like to briefly respond (while perhaps simultaneously reemphasizing previous points I made).

First I would like to address your position regarding the paucity of present information to justify the use of Bup. Just to clarify, I would never suggest that any but the most treatment-resistant and desperate-for-a-treatment patients try such a treatment. However, there have been a few, methodologically rigorous studies of treatment-resistant depressives who got no help from any other treatment, who had a statistically significant benefit from Bup, that often was sustained for years. The ugly truth of Psychiatry though, is that even when using MULTIPLE substances (traditional meds and, even accepted off label ones)) together, administered by the best Psychopharmacologists in ideal circumstances (and even combined with Psychotherapy, exercise, ECT etc),Response rates (defined as a 50% reduction in symptoms) rarely exceed 50%. Remission rates (meaning essentially the depression is gone) are even lower. These figures are not my opinion, but are the consensus view, supported by many studies, even recent ones. So in summary, almost half of all people who seek treatment for depression are unable to achieve a response or remission with any number of combinations of treatments (Psychotherapy, Exercise, Medications, Electroconvulsive Therapy). This fact alone should cause one to consider broadening the therapeutic armamentarium.

Second (and importantly related to the first) is your concern that they might become addicted to opioids. A few things regarding this:

1.) For a variety of reasons, many patients may initially respond well to a treatment, and then gradually or abruptly have a return of their depressive symptoms. This occurs using standard, approved meds and the (in)formal term for it is ”Antidepressant Poop Out”. So the concern over the loss of efficacy that you stated in your scenario for using Bup is not compound-specific (or drug class-specific).

2.) We must operationally define the various components of addiction. Addiction includes dependence, withdrawal, dose escalation, and the inability to stop said behavior/substance even in the face of negative consequences. Many medications induce dependence, but that does not mean addiction accompanies it. For example, people become physiologically dependent upon SSRIs. If stopped abruptly, then very unpleasant withdrawal symptoms appear. Even within the opiate group of drugs, many patients with pain become dependent on opiates, but not addicts. So this is an important distinction that needs to be made.

3.)So in essence, your scenario you describe as cause for concern is already a common occurrence in Psychiatry. Also, the side effects of withdrawal from Bup is no worse than the side effects from SSRIs, SSNRIs or other antidepressants. Fluoxetine may be the most gentle to taper from, due to its very long half life.

So, if a responsible adult with no prior history of substance abuse issues, has depression that is treatment resistant to everything else currently available, and they might benefit from the controlled use of low doses of Buprenorphine, you would still be opposed?

Jana Burson M.D.
7:05 am January 28th, 2011

Yep, still opposed.

My two reasons are 1-I’m not familiar with these rigorous studies of treatment-resistent depressives who were helped by buprenorphine. Can you provide references? I have used medications off-label, as most doctors have, but this is so far outside the mainstream that I’d need some awfully good data to even consider it.

2-It could be harmful to me in my profession. I know some will think I’m being selfish, but as a practical concern, I’d be worried about a lawsuit by a dissatified patient, who now has a physical dependency (you are right, I misspoke, not an addiction) and is still depressed.

I’d also be worried about action against my medical license and/or DEA license. At the risk of sounding like one of the tin-foil hat crowd, doctors who prescribe any opioid outside accepted protocols are targets for regulatory agency investigations.

Jason
2:08 am January 29th, 2011

• Buprenorphine treatment of refractory depression. Journal of Clinical Psychopharmacology. February 1995- Volume 15- Issue 1- pp 49-57
• Antidepressant-Like Effect of Endomorphin-1 and Endomorphin-2 in Mice Neuropsychopharmacology (2007) 32, 813–821
• Chronic Pain Induces Anxiety with Concomitant Changes in Opioidergic Function in the Amygdala Neuropsychopharmacology (2006) 31, 739–750
• CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior December 2009 | Volume 4 | Issue 12 |
• Dysregulation of Endogenous Opioid Emotion Regulation Circuitry in Major Depression in Women Arch Gen Psychiatry. 2006;63:1199-1208
• Imaging of opioid receptors in the central nervous system Brain (2008), 131, 1171-1196
• Kappa-opioid ligands in the study and treatment of mood disorders Pharmacol Ther. 2009 September ; 123(3): 334–343
• Opioid receptors and limbic responses to aversive emotional stimuli. 7084–7089 PNAS May 14, 2002 vol. 99 no. 10
• Modulation of anxiety by µ-opioid receptors of the lateral septal region in mice Pharmacology, Biochemistry and Behavior 83 (2006) 465–479
• Stress Responsivity, Addiction, and a Functional Variant of the Human Mu-Opioid Receptor Gene. Molecular Interventions. April 2007 Volume 7, Issue 2
• Regulation of Human Affective Responses by Anterior Cingulate and Limbic µ-Opioid Neurotransmission. Arch Gen Psychiatry. 2003;60:1145-1153
• Psychotherapeutic Benefits of Opioid Agonist Therapy. Journal of Addictive Diseases, Vol. 27(3) 2008
• Altered levels of basal cortisol in healthy subjects with a 118G allele in exon 1 of the mu opioid receptor gene. Neuropsychopharmacology (2006) 31, 2313-2317
• Emotional perception modulated by an opioid and a cholecystokinin agonist Psychopharmacology (2008) 197:295–307
• The Dysphoric Component of Stress Is Encoded by Activation of the Dynorphin -Opioid System The Journal of Neuroscience, January 9, 2008 • 28(2):407– 414 • 407
• THE ROLE OF AMYGDALAR MU OPIOID RECEPTORS IN ANXIETY-RELATED RESPONSES IN TWO RAT MODELS Neuropsychopharmacology. 2008 November ; 33(12): 2957–2968
• Variation in the -opioid receptor gene (OPRM1)is associated with dispositional and neural sensitivity to social rejection PNAS September 1, 2009 vol. 106 no. 35 15079–15084
• Opioid G protein-coupled receptors: signals at the crossroads of inflammation TRENDS in Immunology Vol.24 No.3 March 2003
• RB101-mediated Protection of Endogenous Opioids: Potential Therapeutic Utility? CNS Drug Reviews Vol. 13, No. 2, pp. 192–205
• 30 Years of Dynorphins – New Insights on Their Functions in Neuropsychiatric Diseases Pharmacol Ther. 2009 September ; 123(3): 353–370

Jason
8:03 am January 29th, 2011

-Opiates as antidepressants. Current Pharmaceutical Design, Volume 15, Number 14, May 2009, pp. 1612-1622(11)

-The Buprenorphine Effect on Depression: By Richard Gracer, published in the NAABT Feb 2007 newsletter. The internet link included above goes to an interview with Dr. Gracer and some of his patients who had treatment resistant depression and are being treated with Sub.

-My apologies for the formatting mess. My bibliographic database software was not cooperating today, so I just opened up the journal articles, and cut and pasted the Title and Journal (was too hurried/lazy to include authors).

-There is one other study of treatment-resistant depressives with Buprenorphine but I could not find a copy of it, so I’ll go look for it on the web and let you know when when I find it.

-Some studies are animal models, but I included many functional neuroimaging studies of the opiate system which have clinical implications.

-If by chance you would like, I could email you any of the above articles as PDF attachments.

-Regarding your practical concerns and your career, I completely understand your apprehension and caution. Since I am neither a practicing physician, nor a PI of my own lab, I have the ”luxury” of not having to worry about such concerns.

geena reardon
1:36 pm April 3rd, 2011

Hello, i’m a pt. who has been treated for pain ( and who has a past history of addiction known to all my physicians), with 30 mg methadone daily. I also am in psychiatry for treatment resistant major depression and anxiety w/ agoraphobia. My last psych, mentioned Bup to me when i was at my wits end quite depressed etc.. I was hoping that where i was already being treated for 5 years with the methadone, could’nt i simply switch to a pain med which could not only help my pain simarily as the methadone, but also give me some antidepression. The medical people said no, they could not-even if they wanted to! Then i came across Bup on my own somewhere online and it mentioned how it can possibly exhibit some relief for depression in those using it. I feel like this is my cgance to try and simply switch from a pain med which they already feel safe with to one (Bup) which could also add some antidepression! I am working on it now with my present psych., who has been very helpful. I am somewaht afraid to bring the thought of changig my pain med up again but i am in dire straits– literally– with nothing at all for my depression. I have gone through every amphetamine and now having been on Desoxyn for 10 years i find it working much less than it used to. However, i still get some energy along with some mild antidepression from it and fact is it’s all i have so i am afraid to throw in the towel while not having anything to replace or even help me somewhat- at all with my depression! I am seen at the MGH in Boston. If you could see your way to write me back with any info for myself and my psych. i would trully appreciate it. Sincerely, geena r.

Jason
5:06 am April 9th, 2011

Hey Geena,

I’m sorry to hear about the various issues you are facing. Were you asking for a reply from myself, or from Dr. Burson? I was just curious because I hadn’t seen Dr. Burson reply to this blog in a while, so if you were trying to reach her this might not be the best way to do so.

If you wanted my perspective I’ve be glad to offer any thoughts, but I am not a physician, I am a research scientist who also has personal experience with treatment-resistant depression.

mommajones
10:01 am May 22nd, 2011

Hello Geena,

I understand you haven’t tried Bup from your blog? I am also a pt with severe and chronic depression and anxiety. I have been on every antidepressant, anti-anxiety, off label prescriptions, out there.
When I tried Subutex for the first time, I felt an extreme uplift in my mood and energy. One year later and I’m still using it to help regulate my mood. When I stay on it religiously, my mood never dips to despare. I am not addicted to it, because I can stop it when I need to (for surgery) etc, and there are no cravings. Maybe that’s just me.
If it matters to anyone, I would vote for letting Bup into the doctors arsenal for treating depression, without the doctor worrying about getting into trouble. Thanks

mommajones
10:04 am May 22nd, 2011

p.s. to my last blog. I heard they are going to market Tramadol as an antidepressant in the future? I’ve heard from many caught in the trap of its addictive properties that it has a way of uplifting mood also. Has anyone heard this, or do I need to be on another site?

Jason
12:18 am May 31st, 2011

Hey mommajones- Tramadol might be a good off-label due to its mild and selective u-opiate receptor and serotonin/norepinephrine reuptake inhibition properties. However, it will most likely not be marketed for such an indication. For one, its already generic, so the profit potential is lacking. Also, it would be “controversial” or taboo, so no company would go that route.

So if you don’t mind me asking, how much subutex do you take per day? Also are you on any adjunct meds or supplements, do any therapy, or exercise regularly?

Thanks for sharing your experiences in this realm!

paul
2:53 pm June 1st, 2011

hello all,

i i quit tramadol about 30 months ago. it was the only med , at the time ,that cured my depression. 4 years ago i was diagnosed as bipolar.

i’ve tried the following as well :seroxat, lustral,prozac, citalopram, escitalopram, duloxetine, venlafaxine, tamezapam, diazepam, lorazepam, librium, ketiapin, lamotrigine, carbemazepine and other mood stabilisers/ anti-psychotics. please forgive me for mixing brand and chemical names.

i have also tried exercise and diet regimes, as well as 12 step processes with AA,CA,NA & CODA. i spent 10 years in psychotherapy.

whatever is wrong with me, it sure is resistant to treatment.

……untill i was prescribed subutex in ’08 to quit tramadol. it instantly made me feel better. i took it for about two years before quitting about 6 months ago – withdrawl was quite bad – as i’d moved to istanbul and the drug isn’t available here.

now i feel ill again and have to leave for home.

and this is the point of my story : i may not be possible for my doctor to prescribe me subutex again as it is contrary to practice policy.

i don’t think that subutex should be prescribed for depression as a matter of course – but as a guaranteed last resort ?

good luck everyone.

Linda
4:07 am June 6th, 2011

After a hip replacement 2 1/2 years ago I was put on Sub to get off the pain meds.

When I was ready to get off of it my psychiatrist suggested using it for long standing, treatment resistant depression and anxiety. He showed me two UK medical journal articles stating that it is being used sucessfully there.

Unfortunately he gave me the highest dose, 32mg. a day. I am currently on 1/4 of a 2 mg. strip a day. It works like a charm.

My body is definitely dependent on it and the withdrawals I experienced while very very slowly reducing the dose were TERRIBLE! I actually ended up in the ER twice.

But, I’d rather be on a low dose of SUB than trudge through life under a heavy veil of depression any day.

My diet most days is healthy, I exercise and take supplements in addition to at least 4 AA meetings a week. I am sober now since 1994.

I don’t abuse the Sub, don’t crave it (as in the obsession of the mind) like I did alcohol when I drank. It simply relieves the depression without leaving me emotionless like the approved ‘anti-depressants’ did.

My two main concerns are libido and damage to my teeth. If anyone can address the oral problems one may or may not experience taking suboxone, I’d appreciate hearing from you. I don’t want my teeth to sustain decay.

In conclusion; I hope that Sub is studied in depth and eventually approved for the use of treating depression because it works for me and I don’t need to increase the dose.

Thank you,
Linda

Jason
6:56 am June 14th, 2011

Hi Linda, glad to hear things are working out well for you. As far as your concerns, here is what little I know. Use the internet, the answer is out there if you research long enough.

1.)Libido- This is one unfortunate side-effect of many things used for depression. I believe opiates indirectly modulate the endocrine system and can mildly lower testosterone levels. Testosterone effects libido in both sexes, although I’m unsure if its as easy for women as is it for men to address theoretical shortage(i.e apply some androgel to skin 1-2 times a day). Obviously in women, it can have unwanted masculinizing effects and other effects as well. Some studies have looked into adjunct medications to improve sexual dysfunction with AD’s. Some have tried Bupropion (which is one of few AD’s without sexual side effects, except occasional improved libido!) Bupropion is mainly effective through its mild re-uptake of norepinephrine and dopamine. Sometimes methylphenidate is prescribed as well. The trouble is, with your history of alcoholism and already being prescribed Sub, its unlikely these would be tried, because it has abuse potential. So Bupropion/wellbutrin might be wortha try. But again, the topic is much more complex and please research more yourself.

2.)Teeth- I have heard some say opiates effected their teeth. There is no physiological mechanism to explain this other than a dry mouth, which many drugs can cause. Drink plenty of fluids, chew gum/brush after meals etc. Ask your dentist though, perhaps there is something to it, but I am doubtful.

Linda
9:45 pm June 14th, 2011

Thanks, JASON for your input.

Linda.

Nomoremommyfood
5:27 am November 11th, 2011

Hi Jason,

I just stumbled on this blog while idly (as in, sick in bed with a cold) researching bupe’s potential as a valid treatment for treatment-refractory depression.

Having read your comments and fully aware of seeming resistance among psychiatric professionals to embrace this option, I’m wondering if you’d be interested in continuing the discussion.

Seeing as the final comment on this post was left about five months ago, let me know if you’re still reading and I’ll attempt to contact you.

Jason
5:45 am December 11th, 2011

Hi Nomoremommyfood-

Yeah, I just randomly check back here to see if anybody else has any opinions, observations etc and I saw your post. If you wanted, give me an email address and I would be more than happy to contact you and talk about anything regarding psychiatry/opiates/neurochemistry etc.

Cameron
4:30 am August 9th, 2012

Very interesting post!

I just want to quickly add that I am 42 and have suffered for over 20 years with ‘mostly’ mild anxiety. The only thing that has helped are opiates – the first of which I took when I was 38 for a fractured rib. It seems obvious to me that if a chemical makes me feel normal it is somehow temporarily affecting the system in the brain that is not working. Just my quick two cents.

On another note, I can empathize very much with Dr. Jana’s fear of repercussion. I find it odd that physical pain can be treated easily with opiates but doctors have regulatory bodies looming over their shoulders when it comes to mental pain.

Thanks for the post!

sdfgsdf
8:22 am April 3rd, 2015

Yes, opioids should be included in depression treatment, in ways that minimize tolerance and addiction. The fact is that ssri and related ‘standard’ antidepressants are not overall very effective, there’s no need in avoiding or ignoring this fact. Science knows nothing about the brain, yet we know what substances are the best for it? They can’t even diagnose severe mental symptoms without interviewing the patient. But to limit antidepressants to serotonin reuptake inhibitors or other monoamine class antdepressants is immoral. The need for better is real. Fortunately there are some non serotonin drugs in the pipe line, including one that’s based on buprenorphine actually, but who knows if they’ll cover everyone not helped by current antidepressants. Basically, at best they should explore as many compounds and neurotransmitters, including opioids, as well as brain changes, brain scans etc, as possible to for once put this condition to rest. Depressed mood ought to be the one thing they can treat effectively, but it isn’t the case for many. Depression or depressive mood is what many self medicate when they score street drugs, yet professional psychiatry often can’t even make a dent, based on the rosy portrayals of current depression treatment many are fooled to believe in it, then learn the hard way of otherwise. At least there are some supplements, but many still just work on serotonin. If serotonin was so wonderful then why don’t depressed people crave serotonin foods instead of chocolate (dopamine), it never ends.

angela
4:16 am June 17th, 2015

I fought addiction to pain medication for over 8 years now. once on suboxone I thought it was the answer to my prayers. as usual I was wrong for they don’t tell you that the withdrawal from suboxone can be just as bad if not worse that hydrocodone/oxycodone pain meds. its a shame they say it can “help” you get off these pain meds but in the end you end up being addicted to a totally different drug instead.

2:22 pm June 17th, 2015

Hi Angela. Cross-addiction is a common thing if you quit taking one medication with the help of another, but continue taking the second one for a long time. It should be prescribed for as long as you have safely quit hydrocodone/oxycodone, and then you should have been also tapered from the suboxone. If you do need main medications, I’m sorry to tell you that there is no way you can use a medication long-term without having your organism develop physical and psychological dependence.

Todd
2:19 am December 16th, 2015

I feel Suboxone along with my supplements works kinda like an antidepressant for me. They are running trials on a new Bupe-based antidepressant I believe. It’ll be for ppl who feel the need to self medicate for their mental issues such as depression and anxiety.

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About Dr. Jana Burson, MD

Jana Burson M.D. is board-certified in Internal medicine, and certified by the American Board of Addiction Medicine. After practicing primary care for many years, she became interested in the treatment of addiction. For the last six years, her practice has focused exclusively on Addiction Medicine. She has written a book about prescription pain pill addiction: "Pain Pill Addiction: Prescription for Hope." Also see Dr. Burson's blog here.

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