Opioids to treat depression?

I’ve seen a couple of bare, obscure mentions of using opioids - specifically hydrocodone (aka Vicodin) - to treat mild to moderate depression, and it just seems counter-intuitive to me. While opioids initially give relief of pain and euphoria, over time, the brain becomes tolerant of and then dependent on it. Also, withdrawal from opioids can cause severe depression.

Then again, I never would have figured some pain relievers can cause rebound headaches. Or intestinal parasites could be useful in treating some auto-immune disorders.

I haven’t found anything on a couple of basic Google searches. Is there anything to this, or is it just wishful thinking?

There is no current generally accepted role for using opiates to treat depression in the US.

By taking opiates, one is substituting an artificial chemical bliss for the symptoms of depression, masking them briefly with a powerful, addicting substance which wears off rapidly with the result that the depressive symptoms come back the same or worse.

That hasn’t stopped some of my patients from asserting that their particular depressions only respond to oxys, or morphine, or similar.

Here is a place to start: Buprenorphine Treatment

Note that doctors must go through a training program to become certified to prescribe Buprenorphine. Some doctors who have not done the training program will prescribe hydrocodone instead.

Evidence indicates it can be helpful but the use of “narcotics” (intentional scare quotes) is one of those areas where the knee-jerk reactions of the powers that be stands in the way of research.

Personal anecdote: After years of trying everything else on the market for TRD (Treatment Resistant Depression) I stumbled upon this idea. My doctor had heard of it but was not certified; he said he would see about getting me an appointment with a colleague who was … meantime we tried hydrocodone. Prescription was to build up gradually to 3 a day but I found that just taking 1/2 twice a day did more for lifting the fog than all the other antidepressants I had tried. Took it for a bit over six months and decided I didn’t need it any more … no problem quitting at all … half a bottle sat in the medicine chest for a couple of years before I threw them out.

As a certified buprenorphine prescriber, I would not advocate its use for treatment of depression at this time, no matter how many testimonials are given in favor of that approach. Data is still insufficient to say it is of benefit. Styudies cited in the link above were small, and even the authors indicated only that buprenorphine might be a possible tool for treating depressive symptoms, and that more studies were needed. Thus far, further studies have not demonstrated any concrete benefit.

Buprenorphine is approved as a treatment for opiate addiction, one of whose symptoms is depression, not for the diagnosis of depressive disorder itself.

While maintenance therapy is an option for many opiate addicts, the goal is to get the patient off buprenorphine eventually, too.

ETA: I am querying one of the experts in the field of psychiatry that likewise uses buprenorphine for opiate addiction treatment, to see if any recent info has escaped my attention. Further updates as info is available.

Turble, I got a page load error when I clicked on your link.

Qadgop, thanks so much for asking around. I’m very interested to hear what you learn.

I just talked to by psychiatry expert, a board-certified pshrink who is also buprenorphine certified, who’s chief of staff at a major psychiatric hospital and specializes in inpatient care, including lots of depressed patients and lots of addicts.

He confirms that while some small studies well over a decade ago indicated that there may well be a very, very small subset of people with refractory primary endogenous depression AND no history of substance abuse who might be able to benefit from judicious use of opiates, there’d be no way that he would ever prescribe opiates for depression, as he’d end up inadvertently treating far, far more folks who would either not benefit from such treatment or be negatively affected by it, for every one person who might benefit.

He’d also have the regulators breathing down his neck.

The link is down for me too now … worked at the time I posted so maybe take a look later.

http://www.NAABT.org National Alliance of Advocates for Buprenorphine

I can only stand by my personal anecdote and the results claimed by the guy I heard it from on another forum board four or five years ago.

I will repeat this statement: “Evidence indicates it can be helpful but the use of “narcotics” (intentional scare quotes) is one of those areas where the knee-jerk reactions of the powers that be stands in the way of research.”

I don’t think that reaction to the word narcotics is a knee jerk reaction. That is the reasonable reaction until we see the science.

Qadgop, please don’t interpret this post as an argument against your or your colleague’s position. IANA doctor or psychiatrist, but I think I’ve found something interesting after reading this thread and doing a little Web searching (not that I imagine I’m the first to find this info).

After first being diagnosed and then backtracking from more than a dozen unsuccessful paths to treat my major depressive disorder, my psychiatrist and I turned to trazodone (Desyrel). For myself, at least, this turned out to be an almost miraculous drug! For most of two full decades, my symptoms vanished completely and my career rose and flourished to a simply astonishing degree.

Trazodone is an old drug but it’s pretty much in a category of it’s own since it’s not an SSRI, not an SNRI, not a NDRI, not a MAOI and not a tricyclic / tetracyclic antidepressant. (BTW: Nefazodone (Serzone), while chemically similar to trazodone, does not help me).

But after reading this very thread about pain-relieving opiates and whether they might help treat depression in certain special cases, I found the following in a PubMed entry on Trazodone

Interesting, no? I can’t help thinking that the hypothesis underlying the proposed mechanism of the drug – i.e., counteracting or treating the patient’s decreased pain threshold – is right on, at least in my case anyway.

Alas, after two decades, the trazodone lost most of its effectiveness for me. I, too, now suffer from TRD and have tried approximately 20 different meds or combinations since. But nothing has ever worked better than trazodone, which I still take today even though that drug’s not *nearly *as effective for me as it used to be.

But here’s the kicker: I occasionally suffer from severe back pain also, so my doctor prescribed Vicodin ES, which contains the opiate pain-killer hydrocodone that, in tandem with the other active ingredient, acetaminophen, is a very effective pain treatment. (For the record, he’s the same physician who is prescribing the trazodone, so he knows everything I’m taking.) I’m very careful to take it only as necessary and only as prescribed (not just to protect my health but to protect my doctor, too!), but that ends up being moderately often (2-3 times weekly).

But when I do, my depression largely melts away for most of a day or more!

I certainly don’t feel “high” for that period (i.e., I feel no drug high), especially since I’ve been taking it for such a long time that the effects are no longer euphoric. It seems to me that there might well be more than a coincidence involved.

On the other hand, I could never be comfortable at all with the idea of regular, daily doses of opiates! Yikes! Who’d want to take that much risk? But I’d imagine that one or two days a week of relief would make the lives of those of us suffering from major depression much less grim and much more tolerable, if not out-and-out enjoyable…

Good post, ambushed. Your experience was much like mine; years of trying to treat chronic major depression with various and sundry antidepressants that had either no effect or only negative side effects, then wham, one little white pill lifts the brain fog and changes everything.

Actually, for me it was only half a pill; I didn’t like the dopiness when I tried increasing the dose … but right there you negate the ‘creating drug addicts’ argument against trying it … it either works within an hour or so or it doesn’t … no need to take it for weeks or months to find out if it is going to work.

Zoe … my point is that without research there will be no science. This is one of those areas where research is being blocked, apparently by some sort of (perhaps faith-based) moral objection, much like the medical marijuana and stem cell issues.

Anyway, the website links are back up … and I have things to do now that I can put up my window shades and face the world again thanks to a little white pill and a doctor with an open mind.

I’ve seen Tramadol, an opioid agonist prescribed off-label for depression.

Someone remind me, please, what an agonist does?

Similar to what an antagonist does, but for non-ants everywhere.

(lame, but I can’t help myself sometimes)

An opiate agonist (morphine, oxycodone, buprenorphine, etc.) activates opiate receptors, causing euphoria, pain relief, cough suppression, sedation, and constipation.

An opiate antagonist (naltrexone, naloxone) blocks the receptors, and doesn’t allow the agonist to activate them.

Hmm… I’d always thought the term applied to say, William Shatner when singing, or anyone at Fox News saying anything at all. Live and learn…

Qadgop, I wish to follow up with you regarding my previous post. Do you happen to know the current status of the “mental pain hypothesis” in psychiatric circles, i.e., does it remain a viable hypothesis? Do you happen to know of any other medication devised under that hypothesis? Do you have any comment in general to my previous post?

Thanks.

Not sure what you mean precisely.

Pain is a broad topic. One of the chief things I have learned is that many (most?) folks tend to somatize all their pain into physical pain. That means any suffering, i.e. emotional (rejected by spouse), psychological (fear of the future), spiritual (not living up to personal morals) disturbances all tend to get identified as physical pain by many patients. They then present the complaint of physical pain to a physician and often get treated with opiates, which does indeed reduce not only the physical, but the other varieties of pain. For a bit.

I’ve written lengthy treatises here in the past regarding the appropriate treatment of chronic pain, feel free to search on my name for them. In them I’ve discussed using antidepressants to treat chronic pain, including using trazodone (it never lived up to early hopes for it in this regard, but it helps some folks, for a bit).

Treatment of chronic nonmalignant pain is usually most successfully done by a multidisciplinary approach which may include non-narcotic pain relievers such as NSAIDS like aspirin, motrin, etc., or Tylenol. But also stretching exercises, aerobic exercise, meditation, biofeedback, medications which change how nerves send pain signals (gabapentin, TCAs, trazodone), and antidepressants as appropriate.

Any underlying psychological disorders need to be addressed also, particularly depression or dysthymia. Getting the person to do meaningful work on a regular basis is important too, paid or unpaid.

Mutual help groups with other folks who are also coping with chronic pain are helpful too. Only rarely do I consider using opiates for chronic non-malignant pain, especially if there is a history of substance abuse.

So much of pain perception and behavior is about patient expectations and mindsets and emotional/psychological states. “Pain thresholds” vary widely not only between different people, but also between different events/circumstances for the same person.

Bottom line: Pain is a symptom, a very complicated one.

Hope that helps. :smiley:

Thanks for that.

But it seems I didn’t make myself clear. I’ve read of trazodone being developed in the context of a very specific interpretation of the phrase “mental pain” that doesn’t seem to fit the intuitive notion of what that means (such as those you’ve discussed). It seems to me that, in the special context I’ve seen it used, it relates to the hypothesis of depression arising from a lowered *threshold *of pain (as opposed to pain itself).

So what I was trying to ask is if you have any idea of whether the hypothesis that “one path to major depression is related to a lowered threshold of pain” is still considered viable. Consider my other questions in that light also, please.

Hi Folks,

I’ve recently been researching buprenorphine for treatment-resistant depression (TRD). My psychiatrist prescribed it yesterday. I’m in a temporary remission right now, but will begin to relapse (like clockwork) in a few days, at which point I’ll start the medication.

Since I will be taking buprenorphine solely for TRD, my doctor did not have to register or obtain a waiver. Under 21 U.S.C. § 823(g), practitioners must register or obtain a waiver from the Substance Abuse and Mental Health Services Administration only if dispensing narcotic drugs “to individuals for maintenance treatment or detoxification treatment.”

Here’s my own informal summary of the published studies/reports about buprenorphine for TRD. Many of them don’t have abstracts. If anyone wants the full studies, just send me an email: awmurawski(at sign)gmail(dot com).

Nyhuis PW, Gastpar M, Scherbaum N. Opiate treatment in depression refractory to antidepressants and electroconvulsive therapy. J Clin Psychopharmacol. 2008 Oct;28(5):593-5

Study included six patients – one week period.

Patients received sublingual buprenorphine as monotherapy in a final dosage of 0.8 to 2.0 mg once daily, beginning with 0.4 mg/d and with successive increases every 1 to 2 days.

Five of 6 patients reached complete remission according to the HAMD score (maximal score, 8 points; physician’s rating) and 4 of 6 according to the BDI (maximal score, 12 points; self-rating).

Nyhuis, P.W., Specka, M. & Gastpar, M. Does the antidepressive response to opiate treatment describe a subtype of depression? European Neuropsychopharmacology 16(suppl. 4), S309 (2006).

Eleven patients – one week period

Then the patients were administered buprenorphine as monotherapy in a final dosage
of 0.8−2.0 mg once daily.

Seven patients responded with a decrease in HAMD and BDI scores of at least 50%.

Callaway E. Buprenorphine for depression: the un-adoptable orphan. Biol Psychiatry. 1996 Jun 15;39(12):989-90.

The author has treated five patients with buprenorhine, with “impressive” results. All five patients were followed for several years, during which “good results were maintained.” No rating scale data is included to assess level of depression before and after initiating treatment.

“Buprenorphine [BPN] in low (circa 0.3 mg qid) transmucosally (under the tongue or by nose drops) can be dramatically effective in cases of treatment for refractory depression.”

Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57.

Ten patients – most over six weeks; some followed longer. Trial period was 6 weeks.

Buprenorphine was initiated at 0.15 mg every morning, intranasally or sublingually. We used the preparation of buprenorphine hydrochloride solution currently marketed in the United States for parenteral administration. This comes in small ampules containing 0.3 mg of the drug in 1 ml of aqueous solution. Dosage was titrated according to tolerance and clinical benefit, with a maximum daily dosage of 1.8 mg.

Three patients unable to tolerate more than two doses.

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.
Three of these remaining seven dropped out at 4 weeks due to side effects, despite dramatic improvement in depression. One of these four improved dramatically during week one, but then relapsed (patient #5)

Two of the remaining four contacted authors at two year point. Doing well. One of them was taking 0.3 mg 3 x daily plus 0.45 mg at bedtime (patient #1). The other was taking 3.3 mg daily (patient #2).

The third of the remaining four did well for six months taking 0.6 mg sublingually 3 x daily. But he relapsed when his outpatient assistance program tried to mobilize him back to full employment, and his father reduced financial assistance. (Patient #3).

The fourth of the remaining four did well for eight weeks, but then relapsed. Her buprenorphine dosage was systematically increased every few days up to a total of 3.6 mg/day, with no benefit.

Mongan L, Callaway E. Buprenorphine responders. Biol Psychiatry. 1990 Dec 15;28(12):1078-80.

Twelve subjects. Response measured on a short mood scale over 2½ hours, and in follow-up interviews the next day.

Subjects were given 1.5 mg buprenorphine sublingually. If no response was noted within 45 minutes, they were given another 1.5 mg.

Eleven were psychiatric inpatients, veterans and most had served in Vietnam. DSM-III-R diagnoses included major depression, schizophrenia, borderline personality, PTSD and bipolar-affective disorder. Most had multiple diagnoses combining one or more of the
above with adjustment, panic or impulse control disorder. The twelfth subject was a normal staff member.

Eight of the subjects had diagnoses including major depression. Six of these were responders. Responders reported increased ability and willingness to talk, (especially about painful topics), with relief of tension-anxiety, anger-hostility and depression. Response was not measured separately for each diagnosis.

Emrich HM, Vogt P, Herz A. Possible antidepressive effects of opioids: action of buprenorphine. Ann N Y Acad Sci. 1982;398:108-12.

Ten patients.

During the four day buprenorphine treatment phase, patients were give 0.2 mg sublingual tablets twice a day.

About 50% of patients responded “very strongly” to buprenorphine; about 50% were nonresponders.

Emrich HM, Vogt P, Herz A, Kissling W. Antidepressant effects of buprenorphine. Lancet. 1982 Sep 25;2(8300):709.

Thirteen patients.

During the four day buprenorphine treatment phase, patients were give 0.2 mg sublingually two times per day.

Four patients showed more than a 50% reduction in depression when they had been on buprenorphine for 203 days; two patients showed a moderate response and four a slight reduction.

For TRD, have you checked into TMS (trans-cranial magnetic stimulation)? This has been FDA approved and is becoming more widely available. The only issue is insurance coverage which is critical since daily sessions are required for several weeks and each one can cost hundreds of dollars.

Here is an article that might give you some useful information - http://www.scientificamerican.com/article.cfm?id=transcranial-magnetic-stimulation-rtms&sc=HLTH_20100831

Thanks, dzero, for the link to the TMS article. A few years ago, I didn’t think TMS looked very effective. Perhaps they’ve made advances? I’ll look at the link.

ECT didn’t do anything but wipe my memory for a few weeks.

I had about a 50% response for 18 months with an implanted vagus nerve stimulator.

I was accepted into a clinical trial for deep brain stimulation, but decided in light of the risks that DBS would be my last option.

IV ketamine worked like a miracle for me. Each 40 mg infusion (0.5 mg/kg) over 40 minutes produced six days of complete remission. But I developed tolerance with weekly infusions, and had to discontinue after four months of having my life back. I think ketamine is very promising if the dosing is managed properly; it should be possible to avoid developing tolerance with prolonged infusions/prolonged antidepressant effects. It should also be possible to get the same effect from oral ketamine. That will be a fall-back option in about six months, after my tolerance has waned – if nothing else is working.

I’ve been using low-level near infrared laser directed at the cerebral cortex for the past two months (per recent Harvard study), and have noticed about a 30% reduction in severity. But I’ve also been getting much better sleep for the past two months due to medication adjustments. Sleep loss causes fierce relapses for me. So it’s not clear whether the near-infrared light is really responsible for the 30% improvement.