Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine

Zhou, Yanling; Wang, Chengyu; Lan, Xiaofeng; Li, Hanqiu; Chao, Ziyuan; Ning, Yuping

doi:10.1186/s12974-021-02245-5

Cited by 34 publications

(44 citation statements)

References 47 publications

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“…Nearly a half of patients with depressive symptoms in our study reported pain symptoms, which was consistent with previous reports ( 6 , 27 ). This finding suggests a high proportion of patients may be resistant to antidepressant treatment, as pain symptoms could negatively impact insight of depression and adherence to medication, which may lead to adverse results ( 3 ).…”

Section: Discussionsupporting

confidence: 93%

“…Ketamine, a novel, rapid-acting antidepressant, has been reported to have therapeutic effects in both pain and depressive symptoms, and may be an ideal treatment option for individuals with depression and comorbid pain symptoms ( 26 , 27 ). For example, a double randomized controlled study showed that daily oral ketamine for 6 weeks is more effective in improving depressive symptoms in chronic pain patients comorbid with mild to moderate depression when compared to diclofenac ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, a double randomized controlled study showed that daily oral ketamine for 6 weeks is more effective in improving depressive symptoms in chronic pain patients comorbid with mild to moderate depression when compared to diclofenac ( 26 ). A separate study conducted by our group has shown that persons with TRD and comorbid pain symptoms are more likely to achieve response and remission than those without pain after receiving six ketamine infusions ( 27 ). The study herein extends the foregoing finding, with evidence of ketamine successfully reducing depressive symptoms in both patients with and without pain.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, peripheral increased cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 have been reported in individuals with the comorbidity of depression and pain ( 41 ). Our previous publication revealed that depressive patients with pain had higher plasma levels of IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) than those without pain, suggesting pain increases inflammatory response in patients affected by depression ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study reported that oral therapy of ketamine for 6 weeks can successfully alleviate depressive symptoms in chronic pain patients ( 26 ). Moreover, our recent publication reported that subanesthetic infusions of ketamine can both reduce depressive symptoms and pain symptoms in individuals with treatment resistant depression (TRD) ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

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Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients

et al. 2022

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BackgroundPain strongly coexists with depression. Ketamine has great analgesic and antidepressant effects, acting as a promising role in treating depression with pain. Few studies have evaluated impact of pain symptoms on antidepressant effect of ketamine infusions. Thus, present study investigated whether pain symptoms in individuals with depression moderate response to ketamine.MethodsOne hundred and four individuals with major depressive disorder and bipolar depression received six intravenous infusions of ketamine. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered at baseline, the next morning after each infusion and 2 weeks (Day 26) after the last infusion. Pain symptoms were collected at baseline using the short-form McGill Pain Questionnaire (SF-MPQ).ResultsThe prevalence of pain in patients with depression was 48.8%. Mix model analyses showed that pre-treatment pain symptoms assessed by each domain of SF-MPQ significantly moderated antidepressant response to six infusions of ketamine from baseline to day 26 (all p < 0.05). Then follow-up simple slopes analyses suggested that all patients across groups showed a significant symptomatic improvement after ketamine infusions (all p < 0.05), and patients with severe pain (across all domains of SF-MPQ) had greater improvement in depressive symptoms than those with mild pain or non-pain (all p < 0.05).ConclusionA significant and rapid improvement in depressive symptoms was observed in patients with depression and pain after ketamine treatment. Ketamine may be a novel and promising antidepressant preferentially for the therapy of depression with severe pain.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients

et al. 2022

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Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain

et al. 2023

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ImportanceRepeated ketamine administration is common in treatment-refractory chronic pain, but ketamine analgesic and antidepressant effects are poorly understood in patients with chronic pain with depression symptoms.ObjectiveTo determine clinical pain trajectories with repeated ketamine administrations, exploring whether ketamine dose and/or pretreatment depressive and/or anxiety symptoms may mediate pain relief.Design, Setting, and ParticipantsThis nationwide, multicenter, prospective cohort study included patients in France with treatment-refractory chronic pain who received repeated ketamine administration, over 1 year, according to ketamine use in their pain clinic. Data were collected from July 7, 2016, through September 21, 2017. Linear mixed models for repeated data, trajectory analysis, and mediation analysis were performed from November 15 to December 31, 2022.InterventionsKetamine administration in cumulative dose (milligrams) over 1 year.Main Outcomes and MeasuresPrimary outcome was mean pain intensity (0-10 on the Numerical Pain Rating Scale [NPRS]), assessed every month for 1 year by telephone, after inclusion in the hospital. Depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), quality of life (12-item Short Form Health Survey [SF-12]), cumulative ketamine dose, adverse effects, and concomitant treatments were secondary outcomes.ResultsA total of 329 patients (mean [SD] age, 51.4 [11.0] years; 249 women [75.7%] and 80 men [24.3%]) were enrolled. Repeated ketamine administration was associated with a decrease of NPRS (effect size = −0.52 [95% CI, −0.62 to −0.41]; P &lt; .001) and an increase of SF-12 mental health (39.7 [10.9] to 42.2 [11.1]; P &lt; .001) and physical health (28.5 [7.9] to 29.5 [9.2]; P = .02) dimension scores over 1 year. Adverse effects were in the normal range. There was a significant difference between patients without and with depressive symptoms in pain diminution (regression coefficient, −0.04 [95% CI, −0.06 to −0.01]; omnibus P = .002 for interaction of time × baseline depression [HADS score ≤7 or &gt;7]). The mediation model showed that ketamine dose was not associated with pain diminution (r = 0.01; P = .61) and not correlated with depression (r = −0.06; P = .32), and that depression was associated with pain diminution (regression coefficient, 0.03 [95% CI, 0.01-0.04]; P &lt; .001), whereas ketamine dose was not (regression coefficient, 0.00 [95% CI, −0.01 to 0.01]; P = .67). The proportion of reduction of pain mediated by baseline depression was 64.6%.Conclusions and RelevanceThe findings of this cohort study on chronic refractory pain suggest that depression (and not ketamine dose or anxiety) was the mediator of the association of ketamine with pain diminution. This finding provides radically new insights on how ketamine reduces pain primarily by dampening depression. This reinforces the need for systematic holistic assessment of patients with chronic pain to diagnose severe depressive symptoms where ketamine would be a very valuable therapeutic option.

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Electrochemical and biosensor techniques to monitor neurotransmitter changes with depression

Dunham,

Venton

2024

Anal Bioanal Chem

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Depression is a common mental illness. However, its current treatments, like selective serotonin reuptake inhibitors (SSRIs) and micro-dosing ketamine, are extremely variable between patients and not well understood. Three neurotransmitters: serotonin, histamine, and glutamate, have been proposed to be key mediators of depression. This review focuses on analytical methods to quantify these neurotransmitters to better understand neurological mechanisms of depression and how they are altered during treatment. To quantitatively measure serotonin and histamine, electrochemical techniques such as chronoamperometry and fast-scan cyclic voltammetry (FSCV) have been improved to study how specific molecular targets, like transporters and receptors, change with antidepressants and inflammation. Specifically, these studies show that different SSRIs have unique effects on serotonin reuptake and release. Histamine is normally elevated during stress, and a new inflammation hypothesis of depression links histamine and cytokine release. Electrochemical measurements revealed that stress increases histamine, decreases serotonin, and leads to changes in cytokines, like interleukin-6. Biosensors can also measure non-electroactive neurotransmitters, including glutamate and cytokines. In particular, new genetic sensors have shown how glutamate changes with chronic stress, as well as with ketamine treatment. These techniques have been used to characterize how ketamine changes glutamate and serotonin, and to understand how it is different from SSRIs. This review briefly outlines how these electrochemical techniques work, but primarily highlights how they have been used to understand the mechanisms of depression. Future studies should explore multiplexing techniques and personalized medicine using biomarkers in order to investigate multi-analyte changes to antidepressants. Graphical abstract

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Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine

Cited by 34 publications

References 47 publications

Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients

Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients

Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain

Electrochemical and biosensor techniques to monitor neurotransmitter changes with depression

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