Comorbidity between Depression and Pain: How Common?1

30-60% co-occurrence rate of major depressive disorder (MDD) and chronic pain reported.

Some subtypes of chronic pain, e.g., fibromyalgia (FM), are very commonly comorbid with psychiatric conditions – debated whether FM is a separate disease condition or a part of MDD symptomatology.

Cumulative evidence suggests that chronic pain and depression do not just co-occur; each one facilitates development of the other, such that chronic pain is a strong predictor of subsequent onset of MDD, and vice versa.





Pain and Depression: Closely Associated Conditions2

Links between acute pain, chronic pain, depression and anxiety2

Genetic predisposition Gender Feeling & beliefs Cultural

Social Education



Actual potential tissue damage

Acute Pain

Chronic Pain

Pain and Depression: Shared Pathophysiology1

Excessive hypothalamic-pituitary-adrenal (HPA) axis and sympathetic activation, combined with elevation of proinflammatory cytokine production and release, likely plays a role in the pathophysiology of MDD and chronic pain disorders.

Other associated factors common for both: Perturbed neuron-glia relationships

Altered glutamatergic, gamma-amino butyric acid (GABA), glycine, substance P, opioid, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) signaling

Dysfunction of intracellular signaling cascades and neurotrophic signaling

Major Depressive Disorder, Chronic Pain, and Risk of Suicide1

MDD and chronic pain each have a well-established association with suicide attempts and completion.

People who suffer chronic pain have a 2-3 fold increase in the risk of suicide compared with healthy controls.

20% lifetime prevalence of suicide attempts noted among chronic pain patients.

Pain and Depression Comorbidity: Implications for Management3

Convergent evidence indicates that MDD and chronic pain amplify each other, contributing to treatment resistance in both disorders.

Because pain and depression share common neurobiological pathways and clinical manifestations, one can use similar strategies and, often, the same agents to treat both conditions when they occur together.

Pain and Depression Comorbidity: Management Options3

Pharmacotherapy of psychiatric disorders in a setting of comorbid pain3

Comorbid state

Depression and pain

Depression, pain, and cognitive complaints

Depression, pain, and fatigue

Recommended agents


SNRIs (?)Vortioxetine

Milnacipran Adjunction bupropion Adjunction modafinil

Depression, pain, and Duloxetine anxiety Venlafaxine

Depression, pain, and TCAs

sleep disturbance Adjunctive gabapentin

Adjunctive pregabalin

SNRI: serotonin-norepinephrine reuptake inhibitor; TCA: tricyclic antidepressant

Antidepressants: Differential effectiveness in pain and depression comorbidity4

Sertraline, escitalopram, venlafaxine – less likely to produce functional benefits in patients with comorbid depression and chronic pain than those without chronic pain.

Amitriptyline – most commonly prescribed antidepressant to individuals with comorbid chronic pain.

Duloxetine – the 2nd most widely prescribed agent.

Amitriptyline, duloxetine, venlafaxine – showed positive association with treatment effectiveness.

Non-drug options for treating chronic pain and depression3

Mindfulness-based therapy

Established efficacy as monotherapy or adjunctive treatment of chronic pain, MDD, and anxiety disorder

Exercise and restorative therapies

Evidence supports adjunct use in treatment of MDD and chronic pain. Exercise improves pain control, mood, cognition, strength, functionally, and cardiometabolic and bone health

aThese are mostly helpful as components of a mind-body integrated treatment of chronic pain and depression

Clear Facts:

Chronic pain and depression are common causes of morbidity.

When the two conditions are comorbid, outcomes are worse.

Also, both are associated with increased suicidality.

Disturbed 5-HT, NE, and DA signaling in the CNS is likely involved.

Management can be difficult and a multi-disciplinary approach is often more effective.

Some select antidepressants (amitriptyline, duloxetine) are found more effective than certain others (sertraline, escitalopram).

Non-drug therapies can be useful adjuncts.

References: 1. Maletic V, DeMuri B. Chronic pain and depression: Treatment of 2 culprits in common – first of two parts. Current Psychiatry 2016 Feb; 15(2):40-52. 2. Michaelides A, Zis P. Depression, anxiety and acute pain: links and management challenges. Postgrad Med. 2019 Sep;131(7):438-444. 3. Maletic V, DeMuri B. Chronic pain and depression: Treatment of 2 culprits in common – second of two parts. Current Psychiatry 2016 March; 15(3):41-52. 4. Roughan WH, Campos AI, García-Marín LM, Cuéllar-Partida G, Lupton MK, Hickie IB, Medland SE, et al. Comorbid chronic pain and depression: shared risk factors and differential antidepressant effectiveness. Front. Psychiatry 2021; 12:643609. doi: 10.3389/fpsyt.2021.643609

Cognitive-behavioral therapy

Has established efficacy as stand-alone or adjunct treatment of chronic pain, MDD, anxiety disorders, and insomnia

Diminishes catastrophizing and ruminations Supports maintenance of improvement

Other behavioral and psychological approachesa



Deep diaphragmatic breathing and relaxation training Guided imagery


Supportive group therapy

Disclaimer: The matter published herein has been developed by clinicians & medical writers. It has also been validated by experts. Although great care has been taken in compiling & checking the information, the authors, shall not be responsible or in anyway, liable for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise however, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields.

For the use of Registered Medical Practitioner or a Hospital or a Laboratory only

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