Efficacy of Antidepressants as Analgesics: A Review

Dharmshaktu, Pinky; Tayal, Vandana; Kalra, Bhupinder Singh

doi:10.1177/0091270010394852

Cited by 274 publications

(213 citation statements)

References 114 publications

(83 reference statements)

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“…Paclitaxel or vehicle (saline) was administered to serotonin (5-HT)/noradrenaline (NA) reuptake inhibitors (SNRI) and selective serotonin reuptake inhibitors (SSRI), have become available and are used clinically as neuropathic pain modalities (5). Newer antidepressants such as those in the SNRI and SSRI classes have been introduced, and their antidepressant function is better understood than that of TCAs.…”

Section: Time Course and Dose-response Of Paclitaxel-induced Mechanicmentioning

confidence: 99%

Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model

et al. 2013

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Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it frequently causes peripheral neuropathy. Milnacipran, a serotonin/noradrenaline reuptake inhibitor and fluvoxamine, a selective serotonin reuptake inhibitor, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of paclitaxel-induced mechanical allodynia in mice by milnacipran and fluvoxamine. Paclitaxel was administered once per day (2 mg/kg, intraperitoneally (i.p.)) for 5 days to mice. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In paclitaxel-treated mice, mechanical allodynia was observed on days 3-15 of paclitaxel administration. A single administration of milnacipran (20 mg/kg, i.p.) or fluvoxamine (40 mg/kg, i.p.) had no effect on paclitaxel-induced mechanical allodynia. However, repeated administration of milnacipran (10, 20 mg/kg, once per day, i.p.) for 5 days significantly reduced paclitaxel-induced mechanical allodynia. In contrast, repeated fluvoxamine administration (40 mg/kg, once per day, i.p.) for 5 days resulted in a weak attenuation of paclitaxel-induced mechanical allodynia. These results suggest that chronic paclitaxel administration induces mechanical allodynia, and that repeated milnacipran administration may be an effective therapeutic approach for the treatment of neuropathic pain caused by paclitaxel treatment for cancer.Peripheral neurotoxicity induced by antineoplastic drugs (taxanes, vinca-alkaloids and platin-based compounds) is a clinically significant complication that can be dose-limiting and can substantially diminish quality of life. Paclitaxel is commonly used for the treatment of solid tumors and ovarian and breast cancers. Paclitaxel induces antimitotic actions by impeding the cell cycle in the late phases of mitosis, stabilizing microtubule formation, and ultimately inducing apoptosis (26). However, paclitaxelinduced peripheral neuropathy is a side-effect of chemotherapeutic treatment which often manifests as bilateral pain in the extremities in a stocking and glove-type distribution (6), sometimes greatly impairing the patients' quality of life and their ability to perform normal activities of daily living. To date, therapeutic drugs have been evaluated using various animal models of paclitaxel-induced allodynia. Ethosuximide (7), gabapentin (14), thalidomide and minocycline (3), neurotropin (11) and acetyl-L-carnitine (8) have been examined against the paclitaxelinduced neuropathic pain model, although studies regarding their efficacy have not been conclusive. Supplementary analgesics (antidepressants and anticonvulsants) have suppressive effects on opioid-resistant neuropathic pain (16,24), and antidepressants are widely used for the treatment of neuropathic pain. Antidepressants, especially tricyclic antidepressants (TCAs), are regarded as first-line drugs for the treatment of neuropathic pain (16). Recently, more selective monoamine reuptake inhibitors...

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Section: Time Course and Dose-response Of Paclitaxel-induced Mechanicmentioning

confidence: 99%

Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model

et al. 2013

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“…Pain is often associated with depression of behavior and mood, and relief from pain-related depression is a common goal of treatment with analgesic drugs (Bair et al, 2003;Cleeland and Ryan, 1994;Dharmshaktu et al, 2012). The mechanisms of pain-related depression are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Pain-Related Depression of the Mesolimbic Dopamine System in Rats: Expression, Blockade by Analgesics, and Role of Endogenous κ-opioids

Leitl

Onvani

Bowers

et al. 2013

Neuropsychopharmacol

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Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. This study tested the hypothesis that pain-related behavioral depression is mediated by activation of endogenous k-opioid systems and subsequent depression of mesolimbic dopamine release. Adult male Sprague-Dawley rats were implanted with electrodes targeting the medial forebrain bundle (for behavior studies of intracranial self-stimulation (ICSS)) or with cannulae for microdialysis measures of nucleus accumbens dopamine (NAc DA). Changes in ICSS and NAc DA were examined after treatment with a visceral noxious stimulus (intraperitoneal injection of dilute lactic acid) or an exogenous k-agonist (U69593). Additional studies examined the sensitivity of acid and U69593 effects to blockade by two analgesics (the nonsteroidal antiinflammatory drug ketoprofen and the m-opioid agonist morphine) or by the k-antagonist norbinaltorphimine (norBNI). The effects of acid were also examined on mRNA expression for prodynorphin (PDYN) and k-opioid receptors (KORs) in mesocorticolimbic brain regions. Both acid and U69593 depressed ICSS and extracellular levels of NAc DA. Pain-related acid effects were blocked by ketoprofen and morphine but not by norBNI. The U69593 effects were blocked by norBNI but not by ketoprofen, and were only attenuated by morphine. Acid did not significantly alter PDYN or KOR in NAc, but it produced a delayed increase in PDYN in prefrontal cortex. These results support a key role for the mesolimbic DA system, but a more nuanced role for endogenous k-opioid systems, in mediating acute pain-related behavioral depression in rats.

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“…Thus, one would expect a better efficacy of dual-or triple-acting agents over selective 5-HT or NE reuptake inhibitors in analgesia (Hache et al, 2011). Several open-label randomized controlled clinical trials, meta-analyses, and systematic reviews have confirmed the clinical efficacy of selected antidepressants in persistent pain conditions (Dharmshaktu et al, 2011). Clinical studies have corroborated that bicifadine is an effective analgesic in the treatment of postoperative pain (Krieter et al, 2008).…”

Section: Clinical Properties Of Trismentioning

confidence: 95%