The Pain-Depression Link
Understanding the Pain-Depression Link
Can antidepressants be used to help manage your pain?
Some effective and commonly used treatments for the relief and management of chronic pain are medications that were developed to treat other conditions.
Although not specifically intended to treat chronic pain, antidepressants are a mainstay in the treatment of many chronic pain conditions, even when depression is not a factor.
People who are diagnosed with depression are more likely to also suffer from chronic pain. However, the mechanism that antidepressants relieve pain, although not yet completely clear, is thought to be separate to the mechanism in which they treat depression.
Therefore, do not be surprised if your doctor prescribes an antidepressant for your chronic pain.

What is the link between depression and pain?
The link between depression and pain works in both directions. If you suffer from a condition that causes chronic pain, like nerve damage, rheumatoid arthritis or fibromyalgia, you are more likely to develop depression.
In fact, studies estimate that people living with pain are 2-5 times more likely to develop depression than the general population, with studies across Europe and the United States indicating that some 85 % of people living with chronic pain experience depression too.
Depression also causes pain. In fact, people seeking help for depression are more likely to present with physical symptoms (including backpain, joint and limb pain, headaches and all-over body aches, as well as digestive problems and fatigue) than the emotional symptoms like apathy and hopelessness; although, the reasons for this are unclear.
Additionally, in general, it is found that the worse the physical symptoms reported, the more severe and longer the depressive episode. In fact, some studies point to chronic pain as one of the most reliable predictors of depression amongst people.
Researchers once thought that the relationship between pain and depression resulted mainly from emotional rather than biological factors. Chronic pain causes emotional suffering and lack of sleep, amongst other depressing symptoms, and likewise major depression can take a physical toll on the body and mind through an elevated and ongoing stress response.
But as researchers learn more about how the brain works, and how the nervous system interacts with other parts of the body, they are discovering that the reason for this close and reciprocal relationship is because pain shares biological mechanisms with depression.
One such reason may be that the sensations of pain and depression are generated and interpreted in similar regions of the brain. The experience of pain, both mental and physical, is generated by the interaction of the somatosensory cortex (the part of the brain that also interprets sensations such as touch) with the amygdala, hypothalamus and anterior cingulate gyrus (areas of the brain that regulate emotions and the stress response). The dysregulation of these same regions also contributes to the development of depression.
It is thought that the neurotransmitters that control mood and typically display abnormal levels in depression – serotonin, dopamine and norepinephrine – contribute to pain signalling in the nervous system in a manner that is not associated with the mechanisms used to control mood. As such, antidepressants that are used to balance these neurotransmitters, namely selective serotonin re-uptake inhibitors (SSRIs) and serotonin and norepinephrine re-uptake inhibitors (SNRIs), may be used to treat pain as well as depression.
Therefore, your doctor may recommend an antidepressant to manage your pain.

Depression hurts
As mentioned, depression and pain often co-exist.
A 2015 study showed a correlation between people who are depressed and impaired pain processing that results in decreased pain tolerance. Similarly, another study in 2010 supported this finding and showed that pain has a greater impact on people who are depressed.
While depression and chronic pain do not have one clearly established cause-and-effect relationship, it is still very important to evaluate them together, especially if your doctor recommends medication. This is because most research suggests that using antidepressants may not only help relieve depression but can also act as an analgesic, effectively combatting pain.
BACKPAIN
One form of pain that is often associated with depression is backpain. It is common to feel okay in the morning, but once at work or sitting at a desk, your back starts to hurt. Although backpain is often associated with bad posture, injuries or spondylosis, they can also be a symptom of psychological distress and depression.
A Canadian study in 2017 found a direct association between depression and backaches in university students. Additionally, previous studies show that, on the other side of the coin, the prevalence of major depression in patients with chronic low back pain is 3-4 times greater than in the general population.
It is also widely believed that depression can cause all-over body aches and pains, but the specifics are still being researched, such as the connection between depression and your body’s inflammatory response. Newer studies suggest that inflammation in the body may interrupt brain signals, and therefore may have a role in depression and how we treat it.
TENSION HEADACHE
Another type of pain strongly linked to depression is headaches. These type of headaches are referred to as “tension headaches,” which may feel like a mild throbbing sensation, especially around the eyebrows, and, unlike excruciating migraines, may not affect your daily functioning to an over-large extent.
However, while these headaches are helped by over-the-counter pain medication, they typically re-occur regularly and can be a symptom of major depressive disorder.

The use of antidepressants to manage pain
Treating both the emotional and physical symptoms of depression is essential to achieving proper management of the condition, and likewise, treating depression in people with chronic pain is needed to achieve maximum therapeutic benefits.
Antidepressants seem to work best for pain caused by:
- Arthritis
- Nerve damage from diabetes (diabetic neuropathy), other peripheral neuropathies, spinal cord injury or stroke
- Tension headache
- Migraine
- Facial pain, such as caused by trigeminal neuralgia
- Fibromyalgia
- Lower backpain
- Pelvic pain
- Pain due to multiple sclerosis
While antidepressants reduce pain signals, they do not work immediately.
You may feel some relief from an antidepressant after a week or so, but maximum relief may take only several weeks. People generally experience moderate pain relief from antidepressants.
Medications from other drug classes with distinct mechanisms of pain relief (such as anticonvulsants) may be used in combination with antidepressants if relief from just the latter is incomplete.
Antidepressants are classified based on their chemical structure and how they work. Along with tricyclic antidepressants, serotonin and norepinephrine re-uptake inhibitors (SNRIs) are the more commonly prescribed forms of antidepressants that you may be prescribed for the management of your pain.
As their name suggests, these medications work to increase the amount of serotonin and norepinephrine (otherwise known as adrenalin) in the brain.
Clinical studies suggest that this dual action is extremely effective at combating depression and preventing the persistence of depressive symptoms. SNRIs may provide be better than medications like selective serotonin re-uptake inhibitors (SSRIs), which only target one neurotransmitter, at achieving remission. Additionally, it has been shown that these medications can be used at the same dosages to effectively treat many types of chronic pain in addition to depressive symptoms, and may be more effective than SSRIs at treating pain as well.
Other types of antidepressants, such as tricyclics are also prescribed for the management of pain, especially neuropathic pain.
To reduce or prevent side effects, your doctor will likely start you at a low dose and slowly increase the dosage of the antidepressant you may be prescribed.
Common side effects associated with SNRIs can include nausea, vomiting and dyspepsia. It is important to note that antidepressant medications are associated with a slightly increased risk of suicidal thoughts or actions.
Talk to a doctor or counsellor promptly if you feel depressed or suicidal. You can also get help here.
You can find out more about depression here and access mental health resources on Let’s Talk.

Sources
- Sansone, R.A. and Sansone, L.A. (2008) Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 5(12):16-19.
- Sheng J, Liu S, Wang Y.; Cui, R.; Zhang, X. (2017) The link between depression and chronic pain: Neural mechanisms in the brain. Neural Plast. 2017:9724371. doi:10.1155/2017/9724371
- Trivedi, MH. (2004) The link between depression and physical symptoms. Prim Care Companion J Clin Psychiatry. 6(Suppl 1):12-16.
- Meerwijk, E.; Ford, J.; Weiss, J. (2013) Brain regions associated with psychological pain: implications for a neural network and its relationship to physical pain. Brain Imaging and Behavior. 7;(1):1–14.
- Zambito Marsala, S.; et al. (2015) Pain perception in major depressive disorder: a neurophysiological case-control study. J Neurol Sci. Oct 15;357(1-2):19-21. doi: 10.1016/j.jns.2015.06.051. Epub 2015 Jul 22. PMID: 26233807
- (2010, June 7) Why does feeling low hurt? Depressed mood increases the perception of pain. ScienceDaily. Retrieved January 12, 2021 from www.sciencedaily.com/releases/2010/06/100607111318.htm
- Kleiber, B.; Jain, S.; Trivedi, M.H. (2005) Depression and pain: implications for symptomatic presentation and pharmacological treatments. Psychiatry (Edgmont). 2(5):12-18.
- Robertson, D.; Kumbhare, D.; Nolet, P.; Srbely, J.; Newton, G. (2017) Associations between low back pain and depression and somatization in a Canadian emerging adult population. J Can Chiropr Assoc. 61(2):96-105.
- Clark, M. (n.d.) Managing chronic Pain and Depression in Arthritis. John Hopkins Arthritis Center. Retrieved January 12, 2021 from: https://www.hopkinsarthritis.org/patient-corner/disease-management/managing-chronic-pain-and-depression-in-arthritis/
- Miller A. (2018). Five things to know about inflammation and depression. Retrieved January 12, 2021 fromhttp://www.psychiatrictimes.com/special-reports/five-things-know-about-inflammation-and-depression
- Krishnadas, R. and Cavanagh, J. (2012) Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. May;83(5):495-502. doi: 10.1136/jnnp-2011-301779. Epub 2012 Mar 15. PMID: 22423117.
- Miller, A. H. and Raison, C. L. (2016). The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature reviews. Immunology, 16(1), 22–34. https://doi.org/10.1038/nri.2015.5
- Headache Foundation (n.d.) Depression and Headaches. Available from: https://headaches.org/2007/10/25/depression-and-headache/
- Robertson, S. (2018) Antidepressants in Pain Management. News Medicine.Net. Retrieved January 12, 2021 from https://www.news-medical.net/health/Antidepressants-in-Pain-Management.aspx
- Jain, R. & S. (2017) Antidepressants in the Treatment of Chronic Pain. PPM. 11,2. Available from: https://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/antidepressants-treatment-chronic-pain
- Marks, D. M.; et al. (2009). Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. Current neuropharmacology, 7(4), 331–336. https://doi.org/10.2174/157015909790031201
- Santarsieri, D. and Schwartz, T. L. (2015). Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs in context, 4, 212290. https://doi.org/10.7573/dic.212290
- Obata, H. (2017) Analgesic Mechanisms of Antidepressants for Neuropathic Pain. J. Mol. Sci.18,2483. https://doi.org/10.3390/ijms18112483
- Moultry, A. and Poon, I. The Use of Antidepressants for Chronic Pain. US Pharm.2009;34(5):26-34. Retrieved January 12, 2021 from https://www.uspharmacist.com/article/the-use-of-antidepressants-for-chronic-pain
- Sussman, N. (2003). SNRIs versus SSRIs: Mechanisms of action in treating depression and painful physical symptoms. Prim Care Companion J Clin Psychiatry. 5.
- Janakiraman R.; Hamilton, L.; Wan, A. (2016) Unravelling the efficacy of antidepressants as analgesics. Fam. Physician. Mar;45(3):113-7. PMID: 27052046.
- Leo, R.J. and Barkin, R.L. (2003) Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for Duloxetine? Prim Care Companion J Clin Psychiatry. 5(3):118-123. doi:10.4088/pcc.v05n0303
- Li, X. and Hu, L. (2016) The role of stress regulation on neural plasticity in pain chronification. Neural Plast. 2016:6402942. doi:10.1155/2016/6402942
- Gold, P.W.; Machado-Vieira, R.; Pavlatou, M.G. (2015) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast.2015:581976. doi:10.1155/2015/581976
- Andrews, L.W. (2010) The Relationship Between Pain, Depression and Mood: An Interview With Rollin Gallagher, MD, MPH. In: ABC-CLIO Encyclopedia of Depression. Santa Barbara, CA: Greenwood Publishing Group; 101.
- Baltenberger, E.P.; Buterbaugh, W.M.; Martin, B.S.; Thomas, C.J. (2015) Review of antidepressants in the treatment of neuropathic pain. Mental Health Clinician. 5(3):123-133.
- Cording, M.; Derry, S.; Phillips, T.; Moore, R.A.; Wiffen, P.J. (2015) Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev. (10):CD008244. doi:10.1002/14651858.CD008244.pub3
- Vadivelu, N.; et al. (2014) Practical guide to the management of acute and chronic pain in the presence of drug tolerance for the healthcare practitioner. Ochsner J. 14(3):426-33.
Sources
- Sansone, R.A. and Sansone, L.A. (2008) Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 5(12):16-19.
- Sheng J, Liu S, Wang Y.; Cui, R.; Zhang, X. (2017) The link between depression and chronic pain: Neural mechanisms in the brain. Neural Plast. 2017:9724371. doi:10.1155/2017/9724371
- Trivedi, MH. (2004) The link between depression and physical symptoms. Prim Care Companion J Clin Psychiatry. 6(Suppl 1):12-16.
- Meerwijk, E.; Ford, J.; Weiss, J. (2013) Brain regions associated with psychological pain: implications for a neural network and its relationship to physical pain. Brain Imaging and Behavior. 7;(1):1–14.
- Zambito Marsala, S.; et al. (2015) Pain perception in major depressive disorder: a neurophysiological case-control study. J Neurol Sci. Oct 15;357(1-2):19-21. doi: 10.1016/j.jns.2015.06.051. Epub 2015 Jul 22. PMID: 26233807
- (2010, June 7) Why does feeling low hurt? Depressed mood increases the perception of pain. ScienceDaily. Retrieved January 12, 2021 from www.sciencedaily.com/releases/2010/06/100607111318.htm
- Kleiber, B.; Jain, S.; Trivedi, M.H. (2005) Depression and pain: implications for symptomatic presentation and pharmacological treatments. Psychiatry (Edgmont). 2(5):12-18.
- Robertson, D.; Kumbhare, D.; Nolet, P.; Srbely, J.; Newton, G. (2017) Associations between low back pain and depression and somatization in a Canadian emerging adult population. J Can Chiropr Assoc. 61(2):96-105.
- Clark, M. (n.d.) Managing chronic Pain and Depression in Arthritis. John Hopkins Arthritis Center. Retrieved January 12, 2021 from: https://www.hopkinsarthritis.org/patient-corner/disease-management/managing-chronic-pain-and-depression-in-arthritis/
- Miller A. (2018). Five things to know about inflammation and depression. Retrieved January 12, 2021 fromhttp://www.psychiatrictimes.com/special-reports/five-things-know-about-inflammation-and-depression
- Krishnadas, R. and Cavanagh, J. (2012) Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. May;83(5):495-502. doi: 10.1136/jnnp-2011-301779. Epub 2012 Mar 15. PMID: 22423117.
- Miller, A. H. and Raison, C. L. (2016). The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature reviews. Immunology, 16(1), 22–34. https://doi.org/10.1038/nri.2015.5
- Headache Foundation (n.d.) Depression and Headaches. Available from: https://headaches.org/2007/10/25/depression-and-headache/
- Robertson, S. (2018) Antidepressants in Pain Management. News Medicine.Net. Retrieved January 12, 2021 from https://www.news-medical.net/health/Antidepressants-in-Pain-Management.aspx
- Jain, R. & S. (2017) Antidepressants in the Treatment of Chronic Pain. PPM. 11,2. Available from: https://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/antidepressants-treatment-chronic-pain
- Marks, D. M.; et al. (2009). Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. Current neuropharmacology, 7(4), 331–336. https://doi.org/10.2174/157015909790031201
- Santarsieri, D. and Schwartz, T. L. (2015). Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs in context, 4, 212290. https://doi.org/10.7573/dic.212290
- Obata, H. (2017) Analgesic Mechanisms of Antidepressants for Neuropathic Pain. J. Mol. Sci.18,2483. https://doi.org/10.3390/ijms18112483
- Moultry, A. and Poon, I. The Use of Antidepressants for Chronic Pain. US Pharm.2009;34(5):26-34. Retrieved January 12, 2021 from https://www.uspharmacist.com/article/the-use-of-antidepressants-for-chronic-pain
- Sussman, N. (2003). SNRIs versus SSRIs: Mechanisms of action in treating depression and painful physical symptoms. Prim Care Companion J Clin Psychiatry. 5.
- Janakiraman R.; Hamilton, L.; Wan, A. (2016) Unravelling the efficacy of antidepressants as analgesics. Fam. Physician. Mar;45(3):113-7. PMID: 27052046.
- Leo, R.J. and Barkin, R.L. (2003) Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for Duloxetine? Prim Care Companion J Clin Psychiatry. 5(3):118-123. doi:10.4088/pcc.v05n0303
- Li, X. and Hu, L. (2016) The role of stress regulation on neural plasticity in pain chronification. Neural Plast. 2016:6402942. doi:10.1155/2016/6402942
- Gold, P.W.; Machado-Vieira, R.; Pavlatou, M.G. (2015) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast.2015:581976. doi:10.1155/2015/581976
- Andrews, L.W. (2010) The Relationship Between Pain, Depression and Mood: An Interview With Rollin Gallagher, MD, MPH. In: ABC-CLIO Encyclopedia of Depression. Santa Barbara, CA: Greenwood Publishing Group; 101.
- Baltenberger, E.P.; Buterbaugh, W.M.; Martin, B.S.; Thomas, C.J. (2015) Review of antidepressants in the treatment of neuropathic pain. Mental Health Clinician. 5(3):123-133.
- Cording, M.; Derry, S.; Phillips, T.; Moore, R.A.; Wiffen, P.J. (2015) Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev. (10):CD008244. doi:10.1002/14651858.CD008244.pub3
- Vadivelu, N.; et al. (2014) Practical guide to the management of acute and chronic pain in the presence of drug tolerance for the healthcare practitioner. Ochsner J. 14(3):426-33.