Antidepressants for the Treatment of Chronic Pain

Department of Psychiatry, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Drugs (Impact Factor: 4.34). 02/2008; 68(18):2611-32. DOI: 10.2165/0003495-200868180-00007
Source: PubMed


Chronic pain represents one of the most important public health problems and, in addition to classical analgesics, antidepressants are an essential part of the therapeutic strategy. This article reviews available evidence on the efficacy and safety of antidepressants in major chronic pain conditions; namely, neuropathic pain, headaches, low back pain, fibromyalgia, irritable bowel syndrome (IBS) and cancer pain. Studies, reviews and meta-analyses published from 1991 to March 2008 were retrieved through MEDLINE, PsycINFO and the Cochrane database using numerous key words for pain and antidepressants. In summary, evidence supports the use of tricyclic antidepressants in neuropathic pain, headaches, low back pain, fibromyalgia and IBS. The efficacy of the newer serotonin and norepinephrine reuptake inhibitors is less supported by evidence, but can be recommended in neuropathic pain, migraines and fibromyalgia. To date, evidence does not support an analgesic effect of serotonin reuptake inhibitors, but beneficial effects on well-being were reported in several chronic pain conditions. These results are discussed in the light of current insights in the neurobiology of pain, the reciprocal relationship between pain and depression, and future developments in this field of research.

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    • "a primary analgesic effect (Max et al., 1992; Fishbain et al., 2000; Finnerup et al., 2005; Atkinson et al., 2007; Verdu et al., 2008; Arnold et al., 2012). SSRIs can augment the activity of a selective NE reuptake inhibitor (Fishbain et al., 2000; Iyengar et al., 2004; Finnerup et al., 2005; Hall et al., 2011), and we hypothesize that an inhibitor with modest selectivity for NET instead would offer the potential for robust pain relief while minimizing any putative serotonergic side effects such as nausea, somnolence, fatigue, and sexual dysfunction (Papakostas, 2008). "
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    ABSTRACT: Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of Central Nervous System (CNS) transporters. We used a translational strategy, including rodent PK/PD modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor (NSRI). TD-9855 was a potent inhibitor of NE and 5-HT uptake in vitro with an inhibitory selectivity of 4 to 10-fold for NE at human and rat transporters. TD-9855 engaged NET and SERT in rat spinal cord with a plasma EC50 of 11.7 ng/mL and 50.8 ng/mL, respectively, consistent with modest selectivity for NET in vivo. Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5 ng/mL and 23.9 ng/mL, respectively. A single dose, open-label PET study (4-20 mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [(11)C]-DASB for SERT and [(11)C] (S,S)-methylreboxetine (MRB) for NET. The long pharmacokinetic half-life (30 - 40h) of TD 9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21 ng/mL, and at doses of greater than 4 mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20 mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35 ng/mL. These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Dec 2014 · The International Journal of Neuropsychopharmacology
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    • "channels, (3) interactions with receptor systems known to participate in pain regulation (acetylcholine, histamine, opioid, α-adrenoceptors, β-adrenoceptors, γ-aminobutyric acid, adenosine, NMDA), (4) inhibition of release of inflammatory mediators; many of these mechanisms potentially may lead to antinociception following systemic administration of antidepressants (Micó et al., 2006; Verdu et al., 2008). In preclinical studies, peripheral administration of antidepressants produces antinociception in models of neuropathic pain (Esser and Sawynok, 1999; Ulugol et al., 2002), and many of the actions contributing to systemic analgesia also may contribute to peripheral activity. "
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    ABSTRACT: Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an overview of the potential for topical analgesics to contribute to improved management of neuropathic pain. Mechanistic and preclinical studies indicate much potential for development of novel topical analgesics for neuropathic pain. In humans, two topical analgesics are approved for use in post-herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8% patch), and there is evidence for efficacy in other neuropathic pain conditions. Comparative trials indicate similar efficacy between topical and oral analgesics. Not all individuals respond to topical analgesics, and there is interest in determining factors (patient factors, sensory characteristics) which might predict responsiveness to topical analgesics. There is a growing number of controlled trials and case reports of investigational agents (vasodilators, glutamate receptor antagonists, α2-adrenoreceptor agonists, antidepressants, centrally acting drugs), including combinations of several agents, indicating these produce pain relief in neuropathic pain. There is interest in compounding topical analgesics for neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of neuropathic pain.
    Full-text · Article · Apr 2014 · European journal of pain (London, England)
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    • "Although evidence supports the use of antidepressants for pain among individuals with major chronic pain conditions [24], an interesting finding in this study was the absence of a relationship between pain and antidepressants use in both bivariate and multivariate models. Absence of the relationship between pain and antidepressant use needs to be interpreted with caution because of a very small sample size of adults without pain. "
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    ABSTRACT: Background Arthritis and depression often co-occur; however, studies that describe patterns of depression treatment among individuals with arthritis are scant. The purpose of the study was to examine depression treatment patterns among individuals with osteoarthritis (OA) by predisposing, enabling, need factors, personal health practices and external health environment. Methods Retrospective cross-sectional design was used. Data were obtained from 2008 and 2010 Medical Expenditure Panel Survey (MEPS). The sample consisted of 647adults aged over 21 years with depression and OA. Depression treatment was categorized as: 1) No treatment;2) antidepressant use only and 3) both antidepressants and psychotherapy (combination therapy). Chi- square tests and multinomial logistic regressions were used to describe patterns of depression treatment. All analysis was performed using Statistical Analysis Software (SAS) version 9.3. Results Overall, 13.0% of the study sample reported no depression treatment, 67.8% used antidepressants only and 19.2% used combination therapy. Among individuals with OA significant subgroup differences in depression treatment were observed. For example, African Americans were less likely to report depression treatment compared to whites [antidepressants: AOR=0.33, 95% CI=0.21,0.51; combination therapy: AOR=0.39, 95% CI=0.23, 0.65]. Elderly adults were more likely to receive antidepressants and less likely to receive psychotherapy as compared to younger adults [AOR=0.53, 95% CI= 0.28,0.98]. Adults with anxiety were more likely to report depression treatment compared to those without anxiety [antidepressants: AOR=1.53, 95% CI=1.06, 2.22; combination therapy: AOR=3.52, 95% CI=2.40, 5.15]. Conclusion Future research needs to examine the reason for low rates of combination therapy as well as subgroup differences in combination therapy among individuals with OA.
    Full-text · Article · Apr 2013 · BMC Psychiatry
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