Replacing Pain with Pain: Hazards of Antidepressant Use for Chronic Pain Relief

The paradox of relieving chronic pain with an antidepressant (and a new set of symptoms)


In a recent German study published this summer in Frontiers in Neurology, researchers report the adverse effects of using antidepressants to reduce chronic pain. Results point to several potential side effects associated with common antidepressants that merit consideration, particularly from a public health perspective.

According to researchers Carina Riediger, Tibor Schuster, Kristian Barlinn, Sarah Maier, Jßrgen Weitz, and Timo Siepmann, patient experiences of chronic pain stemming from a spectrum of conditions (some of mixed or unknown etiology) are commonly addressed through the prescription of antidepressants by medical professionals.

Through meta-analytic assessment of clinical trials of drugs including amitriptyline, nortriptyline, desipramine, milnacipran, venlafaxine, duloxetine, mirtazapine, and fluoxetine to combat chronic pain, researchers identified adverse effects compared to placebo for all antidepressants examined other than nortriptyline. These effects include, but are not limited to, dry mouth, dizziness, nausea, headache, and constipation.

“While multimodal treatment regimens including both pharmacological and non-pharmacological interventions are most effective in the treatment of chronic pain, pain medication is still the second most prescribed group of drugs in the US alone, accounting for 12% of all prescriptions.” write Riediger and colleagues.

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The number of adults, specifically older adults, living with chronic conditions has increased in recent years in tandem with the human lifespan. One explanation for this trend is that people are surviving illnesses and incidents that would have historically proven terminal. Unfortunately, prolonged survival may account for the widespread increase in the human experience of chronic pain.

The study authors report that chronic pain affects 36% of the US population and 19% of the population in Europe. Chronic conditions are often biologically, psychologically, and socially wearing, and represent a substantial financial burden to healthcare systems on an international scale.

Because antidepressants (prescribed in lower doses than when used to treat depression) have been found to relieve pain associated with migraines, fibromyalgia, osteoarthritis, and many other debilitating conditions, Riediger and team sought to examine the tolerability and demonstrated risks associated with this form of treatment.

Following a systematic literature review of clinical trials reporting the results of antidepressants in treating chronic pain, they extracted and cross-compared the sample number of patients, drug used as therapy, and the occurrence of side effects across 69 studies that satisfied inclusion criteria. Further, statistical analyses were conducted to examine factors including differences in incidences of adverse effects, withdrawal due to adverse effects, and differences in specific adverse effect profiles.

Findings from this study warn of higher adverse effects compared to placebo for all but one antidepressant studied, and potential withdrawal symptoms. Co-medication use may also serve to further complicate individual experiences with antidepressants to reduce chronic pain.

The conflict posed by these results is that efforts to manage one’s experience of a certain set of uncomfortable symptoms through the channel of antidepressants may mean substituting one form of suffering for another. As an example, the most prevalent adverse effects found to be associated with amitriptyline use were dry mouth, headache, body weight gain, thirst, and constipation. Although migraines and headaches are two distinct conditions, there is indisputable irony in using amitriptyline to combat one’s migraines and suffering headaches as a result.

Aptly summarized by Riediger and colleagues, “[t]hese findings might be useful in multimodal treatment which takes patient comorbidities and co-medication into consideration. Pathophysiology of the underlying disease, comorbidities, lifestyle, and co-medication should be taken into consideration when determining the use of an antidepressant in patients with chronic pain.”

Temporary solutions for subduing pain should not overshadow the exploration of holistic and non-pharmacological possibilities for relieving the experience of chronic pain for those suffering.



Riediger, C., Schuster, T., Barlinn, K., Maier, S., Weitz, J., & Siepmann, T. (2017). Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis. Frontiers in Neurology, 8. (Link)


  1. Very nicely written. A pleasure to read. Also documents an atrocity in progress. Notable among the unsurprising results were mentions of health statistics. More Americans with chronic health problems might be the demographic effect were told it is, but polypharmacy is as good an explanation. Until I can see that the change in the age distribution fully explains the chronic condition increase, I will stick with an explanation that is not in question. Support comes from the US/EU comparison. That is terrible! Our public health servants should lemming off a cliff for that. It is real suffering and early death in population that shares much of the same ancestral DNA with Europeans, including so-called hispanics whose roots are Spanish, French, and German in addition to Incan, Mayan and Aztec (among others). I don’t blame anyone for personal habits, but when dietary dictates, admonitions to “seek [harmful drug] treatment” for problems in living and use disabling drugs to prevent unlikely diseases, not to mention actual malnutritious food in schools, are handed down from on high, those up high have wronged the nation. (I know the lemming/cliff metaphor is based on a Disney distortion, but in the realm of health-related messaging, Disneyesque distortion is the standard. Transcending it serves one’s dignity but no other object.)

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  2. It really rakes my heart over the coals to see all of the media storm about “opioid crisis” when the dangerous epidemic of psych drugs is not addressed.

    It thrilled me to see this German study – I have made a note of it for when my own doctor tries again to inflict amitriptyline or duloxetine instead of the poppy.

    I’d love to see a similar study (including withdrawal effects) for gabapentin and pregabalin, which are the new “wonder drugs” that doctors seem to be fond of. After all, they can’t be bad since “they’re not opiates.”

    This study was conservative. What numbers I read and could understand did not seem to account for the suicides. Withdrawal effects were mentioned, but were skewed – possibly because of the short-term nature of these studies? (I have seen more trouble with Cymbalta and Effexor, for example, than any tri-cyclic.)

    At Surviving Antidepressants, we have people who were put on these drugs and left on them for 10-15 years. When the drugs stopped working, or the side effects become unbearable – coming off of them is incredibly difficult. While we do have people who struggle with tricyclic drugs – the suffering caused by Cymbalta (one of the most challenging) and Lexapro (escitalopram) are the worst.

    This is the first study I’ve seen that begins to address the problems which are out here in the real world.

    I was hoping to see escitalopram in this study, as it is being handed out left and right as the “best thing since sliced bread.”

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  3. I cold turkeyed off Cymbalta three years ago after my efforts to finally get trauma treatment at age 55 backfired terribly (due to empty promises and outright lies from people I never should have trusted) led to an especially horrendous psych ER visit.

    I had had enough, after 35 years of the systems’ drugs, labels and abuse. They put me through the ringer – ECT, borderline label, forced anti-psychotics. It was hard to get out because I was physically and mentally broken and had been abandoned by everyone.

    I’m still not okay. 3 years of no psych drugs and I still spend most days in bed. I have trouble getting my breath, it takes all the strength I have to shower. Whatever is wrong with me, it’s chronic, probably permanent, and there’s no help. I’m so alone and scared but I know what happens if I “ask for help” so I hide in my apartment, order groceries from Amazon and try not to bother anyone.

    I was probably on 30-35 psych drugs over the years (it began with an elavil prescription at age 17. Why it was prescribed to me is still a mystery. That psychiatrist dropped me the day the board of Ed stopped paying the bills. She gave me no instruction about the elavil.). Cymbalta is different somehow in the havoc it wreaks. It should be banned.

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