Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness

Abstract

The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37–2.54]), recent suicide attempt (OR = 1.88 [1.14–3.09]), higher use of tobacco (OR = 1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68–0.83]), escitalopram (OR = 0.75 [0.67–0.85]) and venlafaxine (OR = 0.78 [0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30–0.67]), escitalopram (OR = 0.45 [0.27–0.74]) and citalopram (OR = 0.32 [0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.

Does Low Grade Systemic Inflammation Have a Role in Chronic Pain?

“…While depression and anxiety have been listed as predisposing risk factors for chronic pain, they are also the most frequent psychological comorbidities of chronic pain ( Kato et al, 2006 ; Tunks et al, 2008 ; Davis et al, 2011 ; Tegethoff et al, 2015 ; Desai et al, 2020 ). These comorbid symptoms of anxiety and depression are associated with decreased chances of recovery ( Nordstoga et al, 2017 ; Roughan et al, 2021 ). It has been reported that psychological interventions such as cognitive behavioral therapy for chronic pain provide small benefits in reducing pain, disability, and distress, or even with worse outcomes if a pro-inflammatory state is present ( Lasselin et al, 2016 ; Williams et al, 2020 ).…”

Impact of CYP2C19 metaboliser status on SSRI response: a retrospective study of 9500 participants of the Australian Genetics of Depression Study

“…Etiological heterogeneity might contribute to individual differences in treatment response [ 6 ] in depression. For instance, comorbid chronic pain, melancholic and anxious depression subtypes have been associated with lower antidepressant response as measured by efficacy and remission [ 7 – 9 ]. Genetic susceptibility also plays a role in antidepressant treatment response [ 10 ].…”

Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review

“…Available pharmacological treatments that target both pain and depression are costly and provide only modest benefits. Participants with comorbid chronic pain and depression specifically report fewer functional benefits from antidepressant use, lower benefits from sertraline, escitalopram and venlafaxine compared to participants without chronic pain, and lower benefits when taking sertraline, escitalopram and citalopram specifically for chronic pain [ 4 ]. The use of antidepressants in chronic pain is associated with moderate efficacy, e.g., ‘limited’ effect in fibromyalgia [ 5 ], ‘small and not clinically important’ effects for back pain [ 6 ], ‘low certainty evidence’ for an effect in osteoarthritis and sciatica [ 6 ].…”