Connect
MJA
MJA

Depression and chronic pain

Alex Holmes, Nicholas Christelis and Carolyn Arnold
Med J Aust 2013; 199 (6): S17-S20. || doi: 10.5694/mja12.10589
Published online: 29 October 2013

This is a republished version of an article previously published in MJA Open

Chronic pain and depression are frequently comorbid.1 The presence of depression in a patient with chronic pain is associated with decreased function,1 poorer treatment response2,3 and increased health care costs.4 An accurate diagnosis of major depression can be challenging in the setting of comorbid chronic pain. Antidepressants and psychological treatments can be effective and are best delivered as part of a coordinated, cohesive, multidisciplinary pain management plan. Here, we describe the current approach to the assessment and management of major depression in patients with chronic pain.

Biological basis of pain

The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.5 Pain can be considered chronic when it persists for more than 1 month after anticipated tissue healing, or if it has been present for at least 3 of the previous 6 months.6 A differentiation is made between neuropathic and nociceptive pain, reflecting different pathological mechanisms, clinical features and treatments. Neuropathic pain is caused by a lesion or disease involving the nervous system. It may have signs of an altered pain response (allodynia, hyperalgesia) and is treated with agents targeting the nervous system abnormality. Nociceptive pain occurs as a consequence of actual or threatened damage to non-neural tissue. It reflects a normally functioning somatosensory nervous system and responds to general analgesics and anti-inflammatory drugs.

Chronic pain is reported by 18.6% of Australian adults. It occurs more commonly in women and those who are poorly educated, unemployed, older, disabled or in compensation systems.6 Common causes are joint arthritis, degenerative disc disease, traumatic injuries and various types of headache.7 Chronic pain can also occur as part of a generalised pain syndrome, such as fibromyalgia.

The emergence of chronic pain has been associated with a range of physical, psychological and social risk factors. These factors interact in complex and dynamic ways, often conceptualised within a biopsychosocial framework.8 Biological research has identified potential mechanisms for chronic pain in nociception, nerve conduction, regulation of spinal cord neurones, neuronal plasticity and gene expression.9 For example, there is evidence that neuroplastic change arising from poorly treated persistent pain can lead to sensitisation, defined as an “increased responsiveness of neurons to their normal input or recruitment of a response to sub-threshold inputs”.10 Neuroplastic change is one possible explanation for the altered pain perception, persistence of pain beyond tissue healing, and resistance to commonly used analgesics that are frequently found in chronic pain.

Pain and depression

The range of pain experiences is wide and varied. An individual’s response to chronic pain reflects characteristics of the pain and the person’s thoughts and behaviour developed during the course of the illness, which are subject to positive and negative reinforcement.11 The daily challenges of chronic pain that are commonly described include decreased enjoyment of normal activities, loss of function, role change and relationship difficulties.8 Uncertainty about ever being pain-free or the possibility of worsening pain are accompanied by feelings of anxiety, sadness, grief and anger. For some people, the burden of pain is difficult to manage and may lead to the emergence of a mental disorder.

Maladaptive responses to pain can, in themselves, worsen the pain experience and further impair function. The presence of catastrophisation, with excessive rumination about the pain, magnification of distress and excessive helplessness, is associated with a poorer response to pain treatments and greater disability.12 For example, in patients with low back pain, a cycle of excessive fear of movement leading to deconditioning, further worsening pain and further fear — termed fear avoidance — has been found to be more predictive of disability than pain intensity.13 Behaviour such as grimacing or groaning, reduced levels of activity, guarding against movement, and the use of protective devices is often linked with negative pain cognitions, and may also hinder recovery.

Major depression is the most common mental illness associated with chronic pain. High rates of generalised anxiety disorder, post-traumatic stress disorder and substance misuse have also been described.14 The lifetime prevalence of major depression in Australia is 11.6%,15 but it is 1.6 times higher in those reporting arthritis.15 In Canada, the prevalence of depression is three times greater in those with chronic back pain.16 In patients with chronic pain presenting for treatment, the prevalence of major depression is 30%–40%.17

There are several ways pain and major depression may be associated, one or more of which may be present in a single patient. First, the psychological and physical distress of persistent pain interacting with individual and social vulnerability may precipitate an episode of major depression.18 Common markers of vulnerability to major depression are a past personal or family history of depression, developmental deprivation, early loss of a parent, and substance misuse.19 Second, depression may be a precursor to, and in some way contribute to, the pain. Pain tolerance is decreased in major depression, and somatic preoccupation can be a prominent symptom, especially in older people. Of note, more than half of the patients presenting with major depression in primary care report some pain.19 In these circumstances, there can be a delay in making the diagnosis, especially when anhedonia predominates over lowered mood. Another proposed mechanism is that chronic pain is a subtype of depression.20 Serotonergic and noradrenergic neurotransmitters have been implicated in both conditions, and they share a clinical pattern of persistence beyond the precipitant. However, there is little other evidence to support this notion. The final way in which chronic pain and major depression may be associated is when both arise out of a common underlying process. This may be a neurological illness, such as multiple sclerosis, or one where the mechanism is not well understood, like fibromyalgia.

Assessment

An assessment of major depression in a patient with chronic pain should be done in conjunction with a pain assessment. A pain assessment characterises the pain, identifies prominent cognitions and behaviour, differentiates nociceptive and neuropathic pain, and determines the impact of pain on function. A comprehensive assessment may include input from a range of disciplines, including pain medicine.

The diagnosis of depression in patients with chronic pain is made more complex by an overlap between depressive symptoms and those relating to the comorbid physical illness and pain (see also Olver and Hopwood, Depression and physical illness).21,22 According to the Diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR), a diagnosis of major depression requires depressed mood or diminished interest or pleasure over 2 weeks, with additional somatic symptoms (sleep disturbance, fatigue, diminished ability to think, weight disturbance) and cognitive symptoms (worthlessness, guilt, suicidality), all leading to significant distress or dysfunction.23 However, most patients with chronic pain describe decreased initiative,18 anhedonia,18 and sleep and appetite disturbance. Several approaches may be used to overcome this diagnostic overshadowing, each representing a different balance of sensitivity and specificity.24

First, the inclusive method allows for all symptoms to be included in making the diagnosis, even if they could be explained by physical illness or pain. This approach has the advantage of simplicity and reliability, but can result in overdiagnosis of major depression.

Second, the exclusive method requires that somatic symptoms are not used, leaving the cognitive symptoms from which to make the diagnosis. Patients with chronic pain and depression are more likely to describe increased sadness, reduced self-worth, lack of meaning and suicidality than those with pain alone,18 giving support to an exclusive approach. The exclusive method deals well with diagnostic overshadowing but at the cost that some cases, including in patients with more severe forms of depression manifest in somatic complaints, might be missed.

Third, using the substitutive method, somatic symptoms of depression are replaced with additional cognitive or affective symptoms. These may include hopelessness, pessimism, irritability, tearfulness, feeling punished, or social withdrawal. There is no consensus on which symptoms can be used as substitutes, nor the total number required.

Finally, the aetiological approach requires judgement by the clinician as to whether the symptoms are related to the physical illness or the depression. This method is supported by the DSM-IV-TR,23 but has the disadvantage of the reduced reliability implicit in making this judgement.

No one approach has a clear advantage over the others. In some cases, the same conclusion will be reached regardless of the method, as in a patient with clear mood change, rumination, pessimism, hopelessness, guilt, low self-worth, and a depressed affect on mental state examination. When the diagnosis is less clear, as in a patient with a fluctuating affect, less prominent cognitive symptoms or marked somatic symptoms, interviewing collateral historians, such as the patient’s family, to determine a clear and persistent change in mental state over time can be useful.

Management

The management of major depression in patients with chronic pain should occur as part of a coordinated approach to pain management, with attention to relevant psychological processes and social issues. In addition to specific interventions, pain management involves identifying and establishing shared treatment goals, collaborative multidisciplinary care and a mutual understanding of the different practitioner roles and responsibilities.

Pharmacological treatment

Research into the pharmacological treatment of major depression in patients with chronic pain has predominantly focused on tricyclic antidepressants (TCAs). TCAs have analgesic properties independent of their antidepressant effect.25 The presumed mode of analgesic action is through enhancing descending spinal noradrenergic and serotonergic inhibitory neurones.26 The doses used in analgesic studies27 and in pain medicine (10–50 mg) are lower than those used for depression (100–200 mg).28 Analgesic studies have demonstrated decreased depressive symptoms alongside reductions in pain, but the treatment of major depression has not been established at these doses. If TCAs are used to treat major depression, antidepressant doses are required.28 Higher doses lead to increased side effects, including sedation, blurred vision, orthostatic hypotension, falls and an increased risk of delirium. Concern about cardiac toxicity, especially in overdose, has led to caution around the use of TCAs as antidepressants. In patients without cardiovascular disease and in whom concerns about self-harm are low, TCAs still have a role, especially when other antidepressants have not been effective. The secondary amines nortriptyline and desipramine are better tolerated than imipramine and amitriptyline in medically ill patients29 and may also be preferable in patients with pain.

A smaller body of research exists in relation to the newer antidepressants and their analgesic properties. Of particular interest are the serotonin–noradrenaline reuptake inhibitors (SNRIs), given their similarities to TCAs. Duloxetine, an SNRI with balanced inhibition of serotonin and noradrenaline reuptake, is effective for both neuropathic30 and nociceptive pain31 — an effect independent of reductions in depression or anxiety. The United States Food and Drug Administration has approved duloxetine for the treatment of fibromyalgia and painful diabetic neuropathy at a dose of 60 mg daily.32 Common side effects of duloxetine are nausea, vomiting, constipation, dry mouth and insomnia, but these are often mild and transient. The evidence for venlafaxine, in which serotonin reuptake inhibition predominates, especially at low doses, is less robust. Case reports33 and some study evidence34 suggest potential for analgesic activity in neuropathic pain at doses of around 75 mg.

The management of comorbid major depression and chronic pain with antidepressants requires clarity around the aims of treatment. TCAs and venlafaxine at analgesic doses are subtherapeutic for major depression. Combining TCAs with selective serotonin reuptake inhibitors (SSRIs) has the potential to induce a serotonergic syndrome. Although there is evidence for response of major depression to duloxetine at doses of 60 mg, some patients require doses of 120 mg.35 To treat major depression effectively, antidepressants need to be used at therapeutic doses for at least 4 weeks, before increasing to higher doses or changing to another agent. SSRIs, which have limited analgesic effect, are often used as first-line treatment of major depression. Among these, escitalopram and sertraline are most efficacious and best tolerated,36 with escitalopram having a low propensity for drug interaction through induction of liver enzymes. Even with optimal treatment, however, antidepressants may not be effective in inducing remission of major depression, especially in the context of severe and prolonged pain.37

Psychological interventions

Psychological therapies are used to treat major depression and reduce depressive symptoms in patents with chronic pain. The most robust evidence for their use in the treatment of major depression is derived from randomised controlled trials involving the general population and patients with other medical comorbidities. In a landmark study, 12 sessions of standardised and adherent cognitive behaviour therapy (CBT) or interpersonal therapy were found to be equivalent to imipramine (200 mg) and more effective than placebo or supportive therapy in treating major depression.38 A study of CBT and antidepressant therapy in patients with multiple sclerosis showed lower rates of major depression in the two treatment groups, compared with the group receiving treatment as usual.39 The negative cognitions challenged in CBT for major depression relate to the world (pessimism), the future (hopelessness) and the self (low self-worth), and the focus of behaviour change is withdrawal and cessation of pleasurable activities. The aim of CBT for major depression is remission and recovery.

Psychological therapies are effective in reducing depressive symptoms in patients with a medical illness40 or chronic pain.41 CBT in patients with chronic pain challenges maladaptive pain cognitions and behaviour, such as catastrophisation and fear avoidance. The aim of CBT in regard to chronic pain is symptom reduction and functional improvement, rather than complete pain relief. Within a multidisciplinary pain program, these methods can increase perceived control and decrease catastrophising, leading to a decrease in pain and depressive symptoms and improved function.42 Techniques that address change, loss, relationship difficulties, acceptance and self-regulation may also be useful.43 Pharmacological and psychological treatments are commonly combined, an approach that has been shown to be effective in the management of depressive symptoms in patients with musculoskeletal pain in primary care.44


Provenance: Commissioned by supplement editors; externally peer reviewed.

  • Alex Holmes1
  • Nicholas Christelis2
  • Carolyn Arnold3

  • 1 University of Melbourne, Melbourne, VIC.
  • 2 Alfred Hospital, Melbourne, VIC.
  • 3 Caulfield Pain Management and Research Centre, Alfred Health, Melbourne, VIC.


Correspondence: acnh@unimelb.edu.au

Competing interests:

No relevant disclosures.

  • 1. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med 2003; 163: 2433-2445.
  • 2. Cherkin DC, Deyo RA, Street JH, Barlow W. Predicting poor outcomes for back pain seen in primary care using patients’ own criteria. Spine (Phila Pa 1976) 1996; 21: 2900-2907.
  • 3. Karp JF, Scott J, Houck P, et al. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry 2005; 66: 591-597.
  • 4. Engel CC, von Korff M, Katon WJ. Back pain in primary care: predictors of high health-care costs. Pain 1996; 65: 197-204.
  • 5. Merskey H, Bogduk N, editors; International Association for the Study of Pain. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. 2nd ed. Seattle, Wash: IASP, 1994.
  • 6. Blyth FM, March LM, Brnabic AJ, et al. Chronic pain in Australia: a prevalence study. Pain 2001; 89: 127-134.
  • 7. Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006; 10: 287-333.
  • 8. Levenson J, editor. Textbook of psychosomatic medicine. Washington, DC: American Psychiatric Publishing, 2005.
  • 9. Pace MC, Mazzariello L, Passavanti MB, et al. Neurobiology of pain. J Cell Physiol 2006; 209: 8-12.
  • 10. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000; 288: 1765-1769.
  • 11. Caltabiano M, Byrne D, Sarafino EP. Health psychology: biopsychosocial interactions. 2nd ed. Brisbane: John Wiley and Sons, 2008.
  • 12. Burns JW, Johnson BJ, Mahoney N, et al. Cognitive and physical capacity process variables predict long-term outcome after treatment of chronic pain. J Consult Clin Psychol 1998; 66: 434-439.
  • 13. Waddell G, Newton M, Henderson I, et al. A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain 1993; 52: 157-168.
  • 14. Demyttenaere K, Bruffaerts R, Lee S, et al. Mental disorders among persons with chronic back or neck pain: results from the World Mental Health Surveys. Pain 2007; 129: 332-342.
  • 15. Australian Bureau of Statistics. National Survey of Mental Health and Wellbeing: summary of results, 2007. Canberra: ABS, 2008. (ABS Cat. No. 4326.0.) http://www.abs.gov.au/AUSSTATS/abs@.nsf/Lookup/4326.0Main+Features12007?OpenDocument (accessed Aug 2012).
  • 16. Currie SR, Wang J. Chronic back pain and major depression in the general Canadian population. Pain 2004; 107: 54-60.
  • 17. Tyrer S. Psychiatric assessment of chronic pain. Br J Psychiatry 1992; 160: 733-741.
  • 18. Nicholas MK, Coulston CM, Asghari A, Malhi GS. Depressive symptoms in patients with chronic pain. Med J Aust 2009; 190 (7 Suppl): S66-S70. <MJA full text>
  • 19. O’Sullivan C. The psychosocial determinants of depression: a lifespan perspective. J Nerv Ment Dis 2004; 192: 585-594.
  • 20. Blumer D, Heilbronn M. Chronic pain as a variant of depressive disease: the pain-prone disorder. J Nerv Ment Dis 1982; 170: 381-406.
  • 21. Pincus T, Williams A. Models and measurements of depression in chronic pain. J Psychosom Res 1999; 47: 211-219.
  • 22. Olver JS, Hopwood MJ. Depression and physical illness. MJA Open 2012; 1 Suppl 4: 9-12.
  • 23. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Publishing, 2000.
  • 24. Cohen-Cole SA, Stoudemire A. Major depression and physical illness. Special considerations in diagnosis and biologic treatment. Psychiatr Clin North Am 1987; 10: 1-17.
  • 25. Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci 2001; 26: 30-36.
  • 26. Ollat H, Cesaro P. Pharmacology of neuropathic pain. Clin Neuropharmacol 1995; 18: 391-404.
  • 27. McQuay HJ, Tramèr M, Nye BA, et al. A systematic review of antidepressants in neuropathic pain. Pain 1996; 68: 217-227.
  • 28. Pilowsky I, Hallett EC, Bassett DL, et al. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982; 14: 169-179.
  • 29. Potter WZ, Rudorfer MV, Manji H. The pharmacologic treatment of depression. N Engl J Med 1991; 325: 633-642.
  • 30. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy or chronic pain. Cochrane Database Syst Rev 2009; (4): CD007115.
  • 31. Chappell AS, Desaiah D, Liu-Seifert H, et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract 2011; 11: 33-41.
  • 32. United States Food and Drug Administration. FDA clears Cymbalta to treat chronic musculoskeletal pain [media release]. 4 Nov 2010. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm232708.htm (accessed Sep 2012).
  • 33. Guldiken S, Guldiken B, Arikan E, et al. Complete relief of pain in acute painful diabetic neuropathy of rapid glycaemic control (insulin neuritis) with venlafaxine HCL. Diabetes Nutr Metab 2004; 17: 247-249.
  • 34. Sullivan M, Bentley S, Fan MY, Gardner G. A single-blind placebo run-in study of venlafaxine XR for activity-limiting osteoarthritis pain. Pain Med 2009; 10: 806-812.
  • 35. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 2002; 63: 225-231.
  • 36. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009; 373: 746-758.
  • 37. Bair MJ, Robinson RL, Eckert GJ, et al. Impact of pain on depression treatment response in primary care. Psychosom Med 2004; 66: 17-22.
  • 38. Roth A, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996.
  • 39. Mohr DC, Boudewyn AC, Goodkin DE, et al. Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. J Consult Clin Psychol 2001; 69: 942-949.
  • 40. Beltman MW, Voshaar RC, Speckens AE. Cognitive-behavioural therapy for depression in people with a somatic disease: meta-analysis of randomised controlled trials. Br J Psychiatry 2010; 197: 11-19.
  • 41. Hoffman B, Papas R, Chatkoff D, Kerns R. Meta-analysis of psychological interventions for chronic low back pain. Health Psychol 2007; 26: 1-9.
  • 42. Jensen MP, Turner JA, Romano JM. Changes in beliefs, catastrophizing, and coping are associated with improvement in multidisciplinary pain treatment. J Consult Clin Psychol 2001; 69: 655-662.
  • 43. Molton IR, Graham C, Stoelb BL, Jensen MP. Current psychological approaches to the management of chronic pain. Curr Opin Anaesthesiol 2007; 20: 485-489.
  • 44. Kroenke K, Bair MJ, Damush TM, et al. Optimized antidepressant therapy and pain self-management in primary care patients with depression and musculoskeletal pain: a randomized controlled trial. JAMA 2009; 301: 2099-2110.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.