Treating Depression with Opioids?

I received this message today:
Hi, you probably answer this quite a bit. I’ve been depressed for as long as i can remember.
Ive been on the ssris, snris, amphetamines and methylphenadate but none of these have worked as well as opiates. (Certainly short term,I don’t take for long periods of time). But have you ever used suboxone or oxymorphone for depression.
Depression is probably a broad term, for what may be multiple conditions. For example, some people become depressed almost as if it is part of their nature— they will get episodes of depresssion even when everything in life is going well, in spite of good marriages, healthy children, and an absence of significant baggage from the past– at least baggage that is visible. Other people will present with depression that has developed after a series of blows to their sense of self or self-worth— after a health scare, job loss, divorce, death of a child, or perhaps from carrying around guilt or shame from abuse that occurred during their childhood.
Does it matter whether the depression is more like the first or the second category? I think so, but I have no proof that my perception is accurate. I will see different responses to medications by people with different types of depresssion, but I’m always challenging that perception, realizing how easy it is to be ‘fooled by randomness’, to copy a phrase from a book title. In my experience, the second person is more likely to bounce back, providing the negative onslaught eventually stops. But the people in the first group are more difficult to treat, especially if the depression becomes part of how a person defines him or herself— as it is very difficult to change self-perception.
When I see someone who describes lifelong depression, my first question is whether the person was ever adequately treated with a good antidepressant. Many times a person will say ‘I’ve taken every antidepressant out there’, but when I carefully go through the history, I find that the person has started many medications, but never took a medication long enough or in sufficient dosage to expect an effect. I will work with such a person, coaxing the person through all of the side effects that led to stopping earlier trials of medications… and many times the person will do well on a medication that was written off years earlier. I think it is important to get this basic info out, before launching into a discussion about more experiemental treatments.
I’ve written in an earlier post about Alkermes trials of a buprenorphine-based antidepressant; I’m not certain where they are in the process with that medication. I do believe that opioids play a role in depression, at least in some people. Many of my patients on buprenorphine say that they feel better on the medication than then remember before taking it. But I realize that all of these people went through very negative experiences as part of their opioid use, before starting buprenorphine. I also know that recollections of emotions are extremely unreliable. It is so important to keep good notes, as a psychiatrist, for this reason. It is common for a patient to insist that he/she felt much better (or worse) the year before….. but then I will read through the chart with the person, and find with the patient that the perception was completely off target.
Even though buprenorphine seems to improve mood in some people, I would be extremely reluctant to prescribe the medication in a person who is not also addicted to opioids– unless or until we find a way to deal with the withdrawal that occurs when stopping buprenorphine. That cost– the difficulty in stopping buprenorphine– is simply too high, to pass on to someone who isn’t already opioid-tolerant.
I should make it clear that I don’t buy into the complaints of people who write about being ‘stuck on buprenorphine’, who started the medication for opioid dependence. I’ve seen enough death from opioids to recognize that buprenorphine is simply a necessary part of treating the majority of people addicted to opioids. Most of the people who complain about being ‘addicted to Suboxone’ somehow have forgotten just how they got on Suboxone in the first place– i.e. the fact that they were stuck on opioids, usually despite multiple trials at stopping on their own. They also seem to have forgotten just how horrible ‘real’ addiction was– a life of getting sick every few hours, with only one true mission in mind– to find the next fix. Being ‘addicted to Suboxone’ is nothing like that world; the unique kinetics of buprenorphine trick the brain out of cravings for the drug, allowing the person to get on with life. There is a huge difference between being ‘stuck’ with a tolerance to buprenorphine vs. active opioid addiction!
I am EXTREMELY interested in the recent findings about ketamine– that several infusions of the drug, in sub-anesthetic dosages, treat depression more quickly than any SSRI. It is very possible that the actions of ketamine relate in some way to the antidepressant effects of opioids. Ketamine acts at NMDA receptors, and also at some classes of opioid receptors. Then again, perhaps the ketamine/NMDA system will be a novel treatment of its own.
To the writer– I noted in your message (the part I removed) that you live in my general area… consider making an appointment, and letting me take a shot at helping you feel better. There are SO many approaches to treating depression, that hopeless cases are rare. I recently had a person find dramatic improvement on an MAOI, after failing everything else over a period of years. People who take opioids now and then usually eventually become regular opioid users– and that would really be a shame.

Endorphin Deficiency Syndrome and Buprenorphine

Every now and then I receive an e-mail or comment that is sufficiently long to warrant a post of it’s own. Below is the comment without interruption; a bit lower I repeat parts of the comment, interspersed with my own responses. I hope you find it interesting.
The comment:
I am a strange case: vegetarian, healthy, Pilates instructor, good-looking– NEVER A DRUG ADDICT — but i had a secret- I was badly depressed for years- treatment resistant to over 30 meds, only some helped to a point… I did extensive research into the brain and opiate systems and i wondered if it was possible my endorphin system may be the culprit ( check this primer:
I was desperate enough to try out opiates as a final solution ( and I monitored myself- I have brakes yet I was always scared of tolerance– and forever afraid to keep on that track) then i found my holy grail… i learned about Suboxone’s other use- ( and it is now being studied for depression)
I was forced to lie to get on Suboxone, i pretended i was an Oxycontin addict etc.. i know that is wrong, but i was trying to save my life ( i was already at the point of suicide attempts)…not only did i get better, i brought my mother in who was also treatment resistant and she was made better also within a week when even ECT failed her and messed up her brain for a good year…..she still takes what i took- 1mg in morning, 1mg in afternoon ( we both sensed that was when we needed a second dose not uncommon believe it or not for other depression sufferers that noticed a drop in the afternoon that Suboxone was again needed)
Anyway she is doing great on it to this day…saved her.
Me after intense meditation for one month- seriously no joke – i sensed i was ready to go off it.
i do everything the hard way- so i went cold turkey off my 2mg a day after being on it for 5 years.
lucky for me- no depression- although the withdrawal did a real number on me– i was so sick from flu and withdrawal , horrible coughing, sore throat, dizzy and weak i wound up at the ER – thought i had H1N1. lol ! I was bed-ridden for almost 2 weeks; i ate nothing for a whole week but soups.
it was NO walk in the park, i was so weak i could not brush the tangles from my hair, even talk much to anyone. and the sweats were out of this world.
i am now at one month and 2 weeks. i still feel kind of weak and sickly, swollen glands, and sometimes a sore throat a little, my face is pale and i have huge dark circles under my eyes… the sweats have almost stopped….but my pupils still dilate… when i exercise i tend to feel worse not better — why is that?
but my real question is this: why does it make me look so pale and dark circles- ??? is it the interrupted sleep?? or low blood pressure or vitamin deficiencies?? Anemia – i take lots of vitamins and 3 iron pills a night (always did as a vegetarian). i only wake up once or twice a night and i take a quarter of sleeping pill – unfortunately- every night still- otherwise i will be up forever..
And is there any nutritional things i can do to make me look less ghastly?? i look like a heroin addict and feel like people will see me that way as i can’t keep saying i have a flu forever !! ! What puts color back in the face ??
* before u lecture me about my terrible lie to the Suboxone doctor ( i think he knows anyway as he had to fudge my notes to make me a worse addict than i claimed) but u know what?? When i was in ER , and could hardly walk straight from my flu + withdrawal–i told the doctor while i felt like i was dying – that even then… i was so happy i took Suboxone – it cured me and my mom FROM A LIFETIME of DEPRESSION.
there IS NO withdrawal that is worth depression, let alone years of it, so please don’t lecture me on what i did, i saved 2 peoples’ lives by lying and i would do it again in a heartbeat…( in fact i was so angry when i found they have a cure for treatment resistant depression i tried in vain to contact media sources to publish a story on it- but who would touch that??)
Wow. I am exhausted. I’m not sure why- but some comments take so much energy to get through—and this was one of those comments. Is it just me?

First things first: Never hesitate to call drug addiction hotlines for help in drug emergency cases.

Some of my answers will likely come across as harsh, and for that I apologize in advance. I don’t wish Edie any bad will, but my comments will probably show that I think she has gotten a bit carried away with some of her ideas. Besides, some of the readers LIKE it when I get obnoxious. Admit it!
My responses—for those of you who still have some energy left:
I am a strange case: vegetarian, healthy, Pilates instructor, good-looking– NEVER A DRUG ADDICT — but i had a secret- I was badly depressed for years- treatment resistant to over 30 meds, only some helped to a point… I did extensive research into the brain and opiate systems and i wondered if it was possible my endorphin system may be the culprit (check this primer:
Most of my friends are drug addicts. Most are not good-looking. They all eat meat—lots of it—and laugh at people in Pilates classes. And they AREN’T depressed. I’m not drawing any conclusions—just pointing out an inverse correlation with an ‘n’ of about 6. I’m also suspicious of the ’30 meds’ comment; it would take a lifetime to give 30 meds adequate trials, even if there were 30 different meds for depression. But I exaggerate too, so no big deal.
The primer is interesting, mainly for the collection of links to articles about the effects of opioids on mood and depression. Edie describes doing ‘extensive research into the brain and opiate systems.’ I don’t know exactly what she did, but the long treatise at the url above is in no way scholarly, but rather is a collection of scattered, mostly-minor studies and comments with many, many incorrect statements, all intended to make the reader believe that there is a unique type of depression caused by deficiencies in the body’s endorphins. I hardly know where to start—but the article, for example, claims that Effexor (venlafaxine) is a good antidepressant in part because of its similarity to the actions of tramadol— and that implies that venlafaxine effects the endogenous opioid system. This is all nonsense. Venlafaxine is an SNRI. Tramadol has effects on norepinephrine reuptake as well. But tramadol has entirely SEPARATE effects on the mu receptor that are NOT shared by venlafaxine.
The comments about acupuncture… there are a host of studies that show a failure of opioid antagonists to block the analgesia produce by acupuncture—evidence for an effect that does NOT involve endogenous opioids (which are blocked by naltrexone).
I honestly could go on and on and on… we know the mechanism of capsaicin on the release of substance P; the effects are a very long shot from thinking that using (or eating!) capsaicin will somehow increase a person’s endorphins. The writer describes a type of patient—a combination of cluster B traits from the DSM, along with assorted personality traits like ‘crying easily.’ Evidently somebody wrote a book. Understand that the current distinctions between mood disorders, while not perfect, are based on hundreds of studies and years of input from psychiatry thought leaders—who then have their opinions examined and tossed around by more thought leaders. Comparing the list of symptoms for ‘endorphin deficiency syndrome’ in the article with the longstanding and scientifically-validated diagnoses from the DSM is like someone writing a poem off the top of his head and saying it belongs in the Bible.
The problem is that there is such a thing as REAL science. I actually DID study neurochemistry and neuroscience during my work for my PhD, and despite that four years of intensive labwork, lectures with distinguished scientists, searching through literature to write and defend my 150-page thesis—despite ALL of that and then my medical school training—I learned about a tiny, tiny bit of how the brain works. The actions of receptors, neurotransmitters, and their relationships to mood and other subjective states encompasses a vast amount of knowledge, much of which contradicts itself from one study to the next. One cannot extract a few studies out of ten thousand and use them to draw conclusions. I’m searching for an analogy… it is like measuring the temperature during one minute from one hour of one day, in a town in Southern Wisconsin, and saying that you therefore understand the climate of the US—and that the US is a rainy and cold place. You would be ignoring all of the other towns, times, and temperatures—and thinking that your point about the US was still valid.
I’m never going to finish this…
I learned about Suboxone’s other use- ( and it is now being studied for depression)
I do recommend that people periodically check to see the interesting studies involving buprenorphine. I would expect other partial agonists to appear on the scene in due course.
I was forced to lie to get on Suboxone, i pretended i was an Oxycontin addict etc.. i know that is wrong, but i was trying to save my life
I’m sorry to interrupt, but this sure sounds like something an addict would say, doesn’t it? Nobody can be ‘forced to lie;’ we CHOOSE to lie because we like what the lie does for us. Maybe it was justified… but ‘forced’? C’mon.
i am now at one month and 2 weeks. i still feel kind of weak and sickly, swollen glands, and sometimes a sore throat a little, my face is pale and i have huge dark circles under my eyes… the sweats have almost stopped….but my pupils still dilate
So much for being good looking! Sorry—just another bitter, bad-looking bald guy…
why does it make me look so pale and dark circles- ??? is it the interrupted sleep?? or low blood pressure or vitamin deficiencies?? Anemia – i take lots of vitamins and 3 iron pills a night (always did as a vegetarian).
Shoot—I was just going to suggest a good T-Bone, medium rare. But seriously, the dark circles can be caused by tiny hemorrhages around capillaries, which tend to be very fragile under the eyes… and the pallor of the skin from vasoconstriction in that part of the body—which is part of opioid withdrawal, along with the ‘goose flesh’ that is so common.
And is there any nutritional things i can do to make me look less ghastly?? i look like a heroin addict and feel like people will see me that way
There you go again, dissing addicts! I’m sorry, but heroin addict don’t all look the same, and they don’t all look ‘ghastly.’ I have patients in my practice who were opioid addicts—some oxycodone, some heroin, most whichever was around— who look like the other people they work with on the job as teachers, carpenters, attorneys, nurses, and CEOs. And no—the thing that will make you look and feel better is TIME.
* before u lecture me about my terrible lie to the Suboxone doctor
Oops—did that already!
please don’t lecture me on what i did, i saved 2 peoples’ lives by lying and i would do it again in a heartbeat…( in fact i was so angry when i found they have a cure for treatment resistant depression….
I NEVER lecture people, but I don’t know if you would get the Nobel prize in Medicine for what you did—although didn’t Al Gore get it for something already anyway?
I’ll stop here. There is no conspiracy, and buprenorphine is not a ‘cure’ for treatment resistant depression. Yes, it does seem to improve mood for SOME people. But there are big downsides—for example the state that you currently are in. You may be positive that you are not an addict, but I’m not; your lie to get yourself on buprenorphine for a while MAY have placed something in you that you cannot yet see, that you will regret some day. If, in five years, you are free of depression and also free of opioids, then it appears that at least in YOUR case, the experiment worked. But frankly, the odds are against you. You will tell me all of the reasons why you are different, and special, and why you will never use again…. But I suspect that if the depression returns, you will have a hard time avoiding another lie for another trial of opioids. If you can’t get buprenorphine but instead buy opioids on the street, you are looking pretty similar to every other opioid addict—ghastly or not.
I have written about this topic before, and included links to some of the things linked on the url that Edie provided. My bottom line? If a person has a history of depression and is an opioid addict, there is one more reason to stay on buprenorphine long-term. But I would have to think very long before conditioning a person to crave opioids—which is essentially what Edie has done. As my treatment-roommate said (about regretting making porno movies with his wife while using), ‘there are some things that we learn, that we cannot unlearn.’ The warm, fuzzy feeling provided by opioids is one of those unlearnable things, and the lesson comes at a steep price—especially in a person who is prone to episodes of depression that only respond to opioids!
I hope I wasn’t too rough, Edie—I do wish you the best.

Buprenorphine (Suboxone) treatment of Refractory Depression

I can’t remember– did I ever point out this article about the use of buprenorphine for depression? I stumbled across it today while looking for something else. The paper is from 1995, about a study done even earlier– well before Suboxone was around.
Here is the abstract:
Opiates were used to treat major depression until the mid-1950s. The advent of opioids with mixed agonist-antagonist or partial agonist activity, with reduced dependence and abuse liabilities, has made possible the reevaluation of opioids for this indication. This is of potential importance for the population of depressed patients who are unresponsive to or intolerant of conventional antidepressant agents. Ten subjects with treatment-refractory, unipolar, nonpsychotic, major depression were treated with the opioid partial agonist buprenorphine in an open-label study. Three subjects were unable
to tolerate more than two doses because of side effects including malaise, nausea, and dysphoria. The remaining seven completed 4 to 6 weeks of treatment and as a group showed clinically striking improvement in both subjective and objective measures of depression. Much of this improvement was observed by the end of 1 week of treatment and persisted throughout the trial. Four subjects achieved complete remission of symptoms by the end of the trial (Hamilton Rating Scale for Depression scores less or equal to 6), two were moderately improved, and one deteriorated. These
findings suggest a possible role for buprenorphine in treating refractory depression. (J Clin Psychopharmacol 1994;15:49-57).
Suboxone Talk Zone

A Controversial Topic

I am considering whether to go forward with this post even as I type this sentence– the comments on depression and Suboxone by Kimmie and ‘Bottlecappie’ are quite thought-provoking and I thank them for their contributions. I am going to post the one by Kimmie ‘up here’; I first want to say though before everyone gets too excited that this topic has several different sides to it, and Kimmie’s is a persuasive version of one side of the discussion. What discussion? The idea that ‘exogenous opiates’– opiates from outside of the body, like oxycodone– have value for treating depression.
It has been known for centuries that opium and related compounds have euphoric or mood-elevating properties. But it has been clear for not nearly as long that there is no way to harness this power for the ‘long run’– whatever benefit is gained short-term must be paid back, many times over, at some point in the future. Now we have Suboxone, and the possibility has been put forward that we can use the euphoric properties of opiates without the negative consequences. I have comments on that idea, and some other problems with the general theory– but I will first post what Kimmie had to say:
Hi. I just began treatment of Suboxone for depression. I also, tried just about every anti-depressant out there over the last 20 years, and have felt depression since I was a child. Although an occasional pot-smoker, I have never been an abuser of pain meds or marijuana, but whenever I had thought of them or had exposure to them (even on TV or films) my brain would light up with desire. Often the cravings were unbearable, out of nowhere, leading to impulsive, harmful and illegal marijuana purchases, folllowed by guilt, remorse, etc….

I did a ton of research and found some info about refractory (treatment-resistant depression) and how perhaps 10-15% of the med-resistant population may indeed have depression due to an inherent lack of natural opiates in the brain. I instinctively suspected this about myself for years with no legal recourse, and then a recent surgery provided more clues. I was on Dilaudid and Vicodin for 5 weeks post surgery and most of my depression symptoms went away…I actually felt “normal” with just one, or even a half a Vicodin a day. My appetite normalized, my mood was clear and even, my sleep was great for a change and my self esteem was strong. And….the withdrawal, even after just 1 pill/day for the last week, was AWFUL. My brain was very sad again. Of course, no one will prescribe pain pills for this purpose….and then I read about Sudoxone. I have just begun Sudoxone, and am still tinkering with dosage as I am very drug sensitive.

I find that if I take the 2mg. Suboxone, split in quarters (.5mg.) and then put it under my tongue for a precisely timed 60 seconds before spitting out -just once a day- I am great! I have since been exposed to marijuana and have forced myself to think about the pill-opiate “high” but for the life of me, I cannot get interested. Prior to last week, I would have been “salivating” in my brain and feeling anxious about calming the urges. That part of my brain that craved the opiates is now quiet and happy. I am hopeful I have found the answer at last! No side effects either. Just a feeling of being myself and being “complete”. Many people may turn to opiates out of natural instincts to find balance, just as a malnourished person seeks just the right nutrients instinctively. I hope this treatment loses its stigma and begins to make its way more into mainstream depression treatment, especially at these minute doses. There is a study here to support my low dosage theory and practice:

also, read here for a ton more info:

It turns out the dose I am approximately taking fits in with the Harvard study’s determination of the optimum dose for depression as well. I just wish they made smaller dose pills so I could have more accuracy.
Hope this can help others,


When I first presented for addiction treatment back in 1993, I was prepared. I had tried to treat myself through knowlege; I already had a PhD in Neuroscience, mainly neurochemistry, I had my ‘MD’, and I was an anesthesiologist. I also read everything I could find on addiction, including 12-step literature; I remember going to the bookstore and finding the ‘Big Book’ of AA, scanning through the steps, pausing for a minute and thinking… Nope– didn’t work. The 12 steps did eventually save my life– twice– but that’s a different story! I went to one of the addictionologists I was ‘screening’– something I now recognize for what it was– addicts (and other people) don’t want to change, so I was looking for a doctor who I would agree with. It is sort of silly, really– I obviously needed new information, as I was getting nowhere… yet I wanted it MY way. That is common– I see it all the time with addiction and with every condition. Patients come in saying they want change, they they do all they can, including lying to me as they pay me my fee, so that whatever I try to do won’t work. Anyway I remember telling this particular addiction doc that ‘I must have a deficiency of endogenous opiates– my endorphin level must be way too low’. He got a good laugh at that.

And he was right to laugh– but this is my concern over posting this info. Almost EVERY opiate addict comes to me and says the same thing– sometimes with big words, and sometimes with smaller words. We ALL think we need opiates! And yet I know from experience that if those people would get clean, either using Suboxone or more importantly to this discussion by using meetings and the 12 steps, they would no longer be depressed. In fact, almost all of the patients who felt they needed more opiates in their brains would be GREAT with recovery alone– much, much better than they were before they even got addicted!

Are there patients who have ‘low opiate levels’? Maybe– but maybe not. Thinking about how the brain works, it is not as if a person has more or less opiate content– just as they don’t have ‘levels’ of serotonin or other transmitters. Yes, you can meaure ‘levels’ in spinal fluid of various chemicals including endorphins, but those are just random molecules that have found their way from the synapse where they work to the spinal fluid– they have no correlation with FUNCTION. The proper dynamic isn’t the amount of a substance, it rather is the action of one neuron upon the other. To illustrate my point, in withdrawal, there are plenty of endorphins around– probably at much higher levels than normal. But the endorphins don’t have the usual effect at the next neuron in the chain, so the brain acts as if the endorphins were not there. Sort of like the old ‘if a tree falls and nobody hears it, did it really happen?’ argument for the old philosophy majors out there.

I have another problem with the ‘opiates for depression’ argument though– it often doesn’t work. There have been studies that look at the use of buprenorphine for depression and they have mixed results. I have at least two patients who wanted bupe for depression, who were also showing strong addictive thinking patterns… and both did poorly with bupe alone. I have one other patient who I ‘inherited’ from another doctor, who was taking bupe for depression– and she has done well on it for three years and counting. But she had no signs of addiction before being placed on buprenorphine.

Or did she? The features of addiction are very similar to features of some of the personality disorders– self-centeredness, a lack of humility, a tendency to rely on others for gratification instead of finding it in ones own abilities, a lack of confidence… a person could make a strong argument that the person who benefits from opiates, who is not an opiate user, is an ‘addict in the making’– and by ‘treating’ the person with opiates we have essentially ‘fed the beast’… and in the long run the beast will destroy the person.

Complicating things, when do we decide that a person is ‘doing well’? Should we rely on the person’s self-assessment? I will often have patients dragged in by a spouse who claims that the person is miserable, isolated, irritable, sick, boring, unsexy, smelly… all because of his/her addiction. The addicted person may say ‘hey, I’m FINE!’ We usually call that ‘denial’… admittedly this is an extreme scenario, but many using addicts will say that they are fine as long as they don’t run out of dope, while it is clear from the outside that the life they are leading is miserable by anyone’s definition. On the other hand I see many people who look like they should be very happy– they have friends, they do well at work, they have nice families… and yet they claim to be totally miserable.

If Kimmie comes to me and says ‘I have an opiate deficiency– off Suboxone I am miserable, and on it I am great– trust me’, and then I notice that on Suboxone she stays in all the time, is moody, can’t keep a job, etc– am I doing her a service by prescribing Suboxone?

Feel free to post your own thoughts or personal experiences on the issue. I have to approve the comments, and I will try to do that as soon as I can after you leave them.

Depression again

Hi, I wrote in this morning asking for your opinion on taking suboxone for depression and severe anxiety. I can not find my post or comment, although I had not signed up for the site until this recent comment. I’m just wondering where my comment went and if it was ever received. I am now registered under the name Larsy. I guess what I am really asking is if I should go off of the suboxone and go back to feeling hopeless, sick with headaches and aches and pains everyday, having no ambition, tired and sleeping all the time, feeling constant anxiety and having panic attacks everyday, overwhelmed and feeling like everyday chores were a tackle to face, getting by with doing just the things that “had to be done” and praying for the evening to come so I could just go to sleep, or if I should stay on the suboxone (2 mgs. per day) and feel like my old self, the girl who loves life and is filled with ambition. If anyone saw my first post from this morning Oct. 17, 2008 signed Laura, or if anyone can help me by sending me your comments, I would really appreciate it. Sincerly – Larsy (Laura)
Hi Larsy,
Given what you are saying, why would you want to stop the Suboxone? My comments about tolerance– the tolerance to buprenorphine develops quite quickly– over a few days. If you have been on it for awhile and you still benefit from it, I would probably keep taking it– especially if it has the dramatic effect that you describe, and nothing else is working. Your post leaves me wondering why you are even asking yourself the question!