Opioids May Cause Depression and Worsen Chronic Pain

“Converging lines of evidence now suggest that depression—a common comorbidity in the setting of chronic pain—may in some patients represent an unrecognized yet potentially reversible harm of opioid therapy.”


A recent article, published in the journal Pain, reviews the evidence that opioids may cause depression. The researchers were led by David N. Juurlink at the University of Toronto, who served on the steering committee of the 2017 Canadian Guideline for Opioid Therapy and Chronic Noncancer Pain. Juurlink writes:

“Converging lines of evidence now suggest that depression—a common comorbidity in the setting of chronic pain—may in some patients represent an unrecognized yet potentially reversible harm of opioid therapy.”

(U.S. Air Force photo illustration/Tech. Sgt. Mark R. W. Orders-Woempner)

Opioids have long been associated with adverse effects ranging from addiction, death due to respiratory problems, and increased risk of falls and accidents, as well as nightmares, hallucinations, and physiological effects such as sweating and nausea. People can experience intense withdrawal effects after even a single use, but withdrawal is typically worsened by long-term use and higher doses. However, the focus of this article is on an oft-overlooked side effect, depression.

Juurlink provides evidence from a number of studies that have linked opioid use, and a higher dose of opioids, to increased risk of depression. For instance, in one study of 1800 people with chronic opioid use, those taking a high dose were about twice as likely to be depressed. They were also more likely to say that opioids were responsible for their depression, while those on a low dose who had mental health concerns suggested that psychosocial factors were responsible for their emotional state.

Another study mentioned in the article found that even among those taking a low dose of opioids, a slightly higher dose was associated with significantly increased depressive symptoms. This was true even when controlling for severity of pain, functioning, and quality of life. Another study found that, independent of pain severity, patients taking opioids were three times as likely to be depressed than those not taking opioids.

Most of these studies controlled for pain severity, functioning, and quality of life, meaning that these factors can’t explain the increased depression in people on high doses of opioids. The researchers discuss previous studies that have suggested why opioids could have this effect.

A review article published in the journal Anesthesiology in 2016 provides thorough evidence that opioids may worsen chronic pain, rather than improving it. The researchers in that article review several mechanisms by which this paradoxical effect may occur.

For instance, according to the researchers, tolerance to opioids may develop very quickly, especially at high doses. As tolerance develops, the drug loses effectiveness, meaning that a higher and higher dose is required to soothe the pain.

Additionally, opioids have been associated with hyperalgesia—a phenomenon in which the body adapts to the presence of the chemical by becoming increasingly sensitive to pain. After an opioid-induced hyperalgesia reaction, painful stimuli become more and more painful. This can lead to increased opioid dosing in an attempt to soothe this pain, which then increases the response, creating intense pain sensitivity. Thus, not only does the opioid stop working in this situation, but it makes a person experience pain more intensely.

These findings have influenced treatment guidelines. For instance, the guidelines for patients at the US Veterans Health Administration provide detail on adverse effects, tolerance and withdrawal effects, and suggest that opioids are not a suitable long-term treatment for chronic pain.

These guidelines also acknowledge the potential that opioids can increase pain sensitivity and may cause depression. They offer a number of alternatives (or supplements) to long-term opioid use, including healthy lifestyle habits, psychotherapies such as ACT and CBT, meditation, and alternative pharmaceutical interventions.



Mazereeuw, G., Sullivan, M. D., & Juurlink, D. N. (2018). Depression in chronic pain: Might opioids be responsible? Pain, 159(11), 2142-2145. doi: 10.1097/j.pain.0000000000001305 (Link)


  1. “… opioids are not a suitable long-term treatment for chronic pain.” Someone educate the doctors, they believe the opioids are “safe pain meds.” And they’re passing them out like candy, under different names.

    I will say that you might want to rethink the title to this article because it might encourage doctors to prescribe the opioids in conjunction with antidepressants. Which is a really dumb idea, since combining the opioids with the antidepressants results in major-major drug interactions, according to drugs.com. And I know from personal experience that doctors are not intelligent enough to check for drug interactions, prior to prescribing drugs.

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  2. Forcing Pain Patients Off Their Meds Won’t End the Opioid Crisis

    A relentless focus on reducing the number and dosage of opioid prescriptions is wreaking hell on people in intractable pain—while failing to treat addiction or reduce overdose deaths

    In Oregon, a state Medicaid committee is now determining whether all existing chronic pain patients on opioids should be forcibly tapered starting in 2020 because of concerns about “overdose and death”— https://tonic.vice.com/en_us/article/7xqa44/forcing-pain-patients-off-their-meds-will-not-end-the-opioid-crisis

    And of course people on opiates are depressed cause chronic pain patients are treated the same as people on probation for criminal offences.

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    • littleturtle

      You said: “who knows what lurks in our brains…”

      This sound quite ominous and actually reminds me of biological psychiatry’s “genetic theories of original sin.”

      I would say that nothing “lurks” within the human brain.

      IT, just like the actual person the brain resides in, is basically innocent and a clean slate at birth. It is the subsequent human interaction with the surrounding environment over time that determines what takes place in the brain.

      Love and nurturance will create a good result. Trauma and high levels of stress, not so much.


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  3. Not only that but the combo of meds I was prescribed at my first visit to the doctor about my pain included the opioid Tramadol and the muscle relaxer Flexeril, which have a known interaction of causing depression and potentially psychosis. My *first* visit, no psych issues discussed, just pain, extreme fatigue, GI issues and trouble sleeping. What a difference a lyme diagnosis would have made in place of years of fibromyalgia labeling and prescribing of harmful pharmaceuticals making me sicker and sicker as my body succumbed to the ravages of the borellia spirochete.

    Man, can’t beat all this awesome medicine in the 21st century….

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  4. before the media declared the opioid deaths an “epidemic,” psychiatry was leaning towards bringing opioids back into use for “mood disorders.” I’ve read abostracts on suboxone for depression, bipolar, strong pain killers for add on treatment in psychosis…

    and now opioids are demonized, and so are those who need them, many of whom are already low status, suffering, etc. Psychiatry, Inc. is a-OK, though…have y’all seen the ads for Suboxone long acting injection? once a month shot, apparently keeps cravings at bay. The profiteers are profiting, will profit, no matter what “crisis” hits next…

    meanwhile, law enforcement and the medical establishment (as a whole) get more powerful, Mental Health, Inc. gets -even more- power and profit and funding from all over, and freedom and freedom of thought continue to die a slow, agonizing death.

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    • Yeah, low dose suboxone has been suggested as a treatment for Lyme Disease as well. It’s due to the off label prescribing that doctors are so strongly pressured (illegally) by their pharma reps to do.

      As for opioids and chronic pain, there’s little to suggest that the people who’ve fallen prey to their use are actually being helped. One of my sisters alternates between morphine and methadone for her severe disfiguring autoimmune arthritis. She’d likely get more relief from weed but until that becomes legal where she lives, she won’t touch the stuff, instead opting to sleep her life away on hard legal drugs.

      Of course, that current patients are being hurt by overzealous deprescribing practices isn’t really in contention. But just like the benzo debate, it would be better if the initial prescription could be prevented. Once you’ve got someone hooked on narcotic painkillers, it’s hard to convince them to try anything else. The withdrawal from these drugs is killer and worse than the initial pain they were prescribed for.

      Simply put, patients are being hurt all the way around, no matter how this issue is examined.

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      • Good comment, Kindredspirit.

        It is amazing how Big Pharma and psychiatry constantly develops strategies of “repurposing” (through “off label’ prescibing) their drugs when they need to further maximize their profit levels at the people’s expense.


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  5. CatNight

    You said:”A relentless focus on reducing the number and dosage of opioid prescriptions is wreaking hell on people in intractable pain—while failing to treat addiction or reduce overdose deaths”

    Yes, it is wrong to recklessly rip people off of pain drugs. Responsible medicine needs to develop a very comprehensive and long term plan to help these people. This is especially true since THEY are responsible for this crisis of irresponsible “treatment.”

    But their needs to be a DRAMATIC reduction in the prescription of pain drugs in the future, especially beyond a few weeks. Log term use not only does not work but makes people worse off.


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  6. Another reason why depression is a side effect (or main effect) of long term opiate use, is because people have expectations that they will feel better over the long run. These hopes are dashed on the rocks of reality.

    And then as people rely more and more on pain drugs (and don’t get better) their physical activity (basically no exercise) comes to a screeching halt. This lack of exercise becomes a major contributing factor to the onset of depression.


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    • How do you know this ? Seems to me if it hurts to move people are going to do less moving.

      This debate is for people with chronic pain to be having not for us as outside observers that’s why I always paste in links to their websites. They know whats best for them more then we do.

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      • I agree with Richard about the impact of exercise on feelings of emotional well-being and that chronic pain patients are losing out with the current method of drugging them beyond coherent functioning. As someone who has personally lived with chronic pain for decades and had my share of pain pills and surgical interventions, yes, it’s a shame that even low impact therapeutic movement is further limited for chronic pain patients. And yes, Richard is right that the opioids further reduce a person’s likelihood of getting any exercise at all.

        Structured physical therapy for people with limited mobility and chronic pain including things like massage, heated pool swimming, yoga, etc would be much more useful than just knocking people out with drugs, but insurance almost never pays for PT for longer than the time it takes to recover from an acute injury because pharmaceuticals are cheaper.

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  7. On the subject of 12 Step I believe there’s a basic rule (in life) that says that anything a person takes to relieve anxiety will make the anxiety worse in the long run.

    (I’m not good under physical pain, and if I was in real pain I would probably take anything to relieve it).

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  8. I’m finding myself agreeing more and more with Szasz, when it comes to the prescription drug system…eliminate it. If the prescription system was eliminated and -all- drugs were available, then costs would go down, the doctor-patient relationship would probably become more humane and ethical, and various “drug epidemics” would become a thing of the past. and yet…


    So, for now, it appears that the “solution” is to further terrorize the poor and working classes by cutting off pain killers and demonizing those who need them to get thru the day, while the “respectable” pain killer users can have their little bit of Lortab, etc., plus hands off Suboxone treatment if needed…

    and the well to do and rich opioid users will mostly continue finding “proper treatment,” perhaps with a small reduction in quantity and/or potency of the drug(s) in question. Nothing wrong with that, btw…I don’t have a problem with the upper classes, I just hate that one needs to be in the top 10-20% in the US (in particular…) to be treated with any basic decency, and not just in the realm of pain management.


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    • Been off thyroid medicine for 3 weeks. Couldn’t find a prescriber thanks to a Medicaid card glitch.

      Lucky my cancer doctor was nice enough to write one. (No cancer, but pernicious anemia and other deficiencies thanks to decades on my psych cocktail. Iatrogenic disease is real!)

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