A Study on Electrocardiographic Changes Secondary to the Use of Tricyclic Antidepressants in Patients with Chronic Pain

Cunha, Ricardo Joaquim da; Barrucand, Louis; Verçosa, Núbia

doi:10.1590/s0034-70942009000100007

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…Recently, the first antidepressant (Duloxetine), administered as a capsule comprising enteric coated pellets, has been approved for the management of diabetic peripheral neuropathic pain [6]. Amitriptyline, doxepin and imipramine (drugs that nonselectively block the reuptake of monoamines) appear to express the most potent analgesic effect [4], and its chronic use seems to be safe and effective [7], even more that other local anesthetics like bupivacaine or lidocaine [1,[8][9][10]. Intrathecal amitriptyline reverses thermal hyperalgesia induced by carrageenan in a dose-dependent manner [11] and given systemically, the drug is effective in alleviating thermal hyperalgesia induced by spinal nerve ligation [12].…”

Section: Introductionmentioning

confidence: 99%

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

García¹,

Escribano²,

Colom³

et al. 2011

CNANO

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Tricyclic antidepressants (TCAs) have potent local pain blockade properties that could be of interest in relieving chronic pain states as neuropathic pain. The aim of this work was to reach a persistent control of nociceptive and neuropathic pain by means of an injectable controlled release system using lower than usual doses of TCAs. To address this issue, amitriptyline, doxepin and imipramine were encapsulated with poly (lactic-co-glycolic) acid (PLGA) as polymer. Nanoparticles were characterized. The in vitro drug release profile and mechanism was evaluated, and the in vivo analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury, respectively, was tested. The mean±SD particle size and drug loadings (%) of the nanoparticles obtained were 420±13, 480±73 and 373±25nm, and 40.46±4.11, 31.09±3.02 and 32.20±3.20 % for amitriptyline, doxepin and imipramine, respectively. According to the Korsmeyer-Peppas model, the release mechanism of doxepin was diffusion controlled, while a combination of Fickian diffusion and polymer relaxation/erosion of the PLGA matrix was involved for amitriptyline and imipramine. After local infiltration of nanoparticles in rats, the antinociceptive and anti-allodynic activity of the encapsulated drugs were long-lasting and higher than that observed from the solutions. Amitriptyline elicited the lower analgesic effect. Doxepin showed the most outstanding results and its encapsulation led to a 62% and 229% increase in antinociceptive and anti-allodynic activity, respectively. So, this drug could be considered as a therapeutical alternative in pain relieving treatments.

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Section: Introductionmentioning

confidence: 99%

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

García¹,

Escribano²,

Colom³

et al. 2011

CNANO

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“…The CHMP 2017 assessment report [28] [18] included mixed studies conducted in neuropathic pain in which no significant impact on QTc was seen [21] or amitriptyline was reported to have significantly prolonged the QTc interval [22], although to a lesser extent than observed with doses used in depression. Caution is recommended in generalizing data, with practical distinction between studies on QT prolongation in overdose or toxicity, as opposed to standard clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…Bazett's prevails as the most popular route for obtaining QTc, despite Fridericia's correction possibly being more precise at the extremes of physiological heart rate [13], as may be the case in patients receiving TCA therapy [17,18]. A number of published studies evaluating QTc prolongation and amitriptyline use, either specify the use of Bazett's formula in their methods, or lack details on which formula was used for QT interval correction [14,[19][20][21][22][23][24][25]. Such array of data emerging in the literature and adverse events reported during the post-marketing period, as collated in the EU database of suspected adverse drug reactions (ADRs)-Eudravigiliance, serve to update the official sources of product information.…”

Section: Introductionmentioning

confidence: 99%

Safety Implications of Low-Dose Amitriptyline in Neuropathic Pain

2019

Pharm Front

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Background: Treatment guidelines in neuropathic pain list amitriptyline as a first-line option. Modest evidence on efficacy and safety concerns possibly shape the rationale behind dosing recommendations. An observational study was carried out to understand the usefulness of safety monitoring for this established medicine. Methods: Twenty-six (26) subjects were categorized into 2 groups: 13 patients under pain management receiving 10 mg amitriptyline daily for less than 12 months, and 13 patients under psychiatric care receiving a daily dose of 25-75 mg for over 12 months. Dose-related reference ranges were calculated and blood levels were assessed for the case examples presented. Adverse events and ECGs were collated. QT intervals were corrected using Bazett's and Fridericia's formulae. Side-effect frequencies were evaluated both within the research groups, and in the broader perspective of spontaneous ADR reporting through EudraVigilance. Results: The applicability of dose-related reference ranges, considering confounding factors such as drug interactions and metabolizer status, is discussed. Patients in both groups reported on average three side-effects, with drowsiness being reported more significantly in the 10 mg group and possibly attenuating with time; an observation not replicated for dry mouth. ADR reports with non-granulated information limit the usefulness of the data retrieved. Comparison of QT corrected with Bazett's and Fridericia's formulae suggests that Bazett's may overestimate the number of patients on amitriptyline with QTc prolongation. Conclusions: This research supports the adoption of evolving research observations to understand the implications of dosing recommendations

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“…Antidepressants are a mainstay of the treatment of many chronic pain conditions, even when depression is not a factor [38] and its chronic use seems safe and effective [39] . Their potential value as analgesics has recently been confirmed by the approval of the first antidepressant (duloxetine) for the management of diabetic peripheral neuropathic pain [40] .…”

Section: Discussionmentioning

confidence: 99%

Analgesic and Antiallodynic Effects of Antidepressants after Infiltration into the Rat

García

Valle²,

Escribano³

et al. 2010

Pharmacology

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Tricyclic antidepressants (TCA) have potent local anesthetic properties and may produce a long-lasting pain blockade that could be of interest in relieving chronic pain states such as neuropathic pain, but there are only few data comparing their dose-response curves of analgesic activity under the same experimental conditions. This study examines the time course of pain-relieving properties of 7 TCA in heat-induced paw withdrawal after subcutaneous administration. Mixed inhibitors of norepinephrine and serotonin uptake (amitriptyline, nortriptyline, imipramine, desipramine, doxepin) and selective inhibitors of serotonin uptake (fluoxetine and fluvoxamine) were assayed. The TCA with the longest analgesic activity were selected to test its antiallodynic effect in the neuropathic pain model of chronic sciatic nerve constriction injury. Bupivacaine was used as a reference drug in both experiments. A dose versus time of maximal analgesic effect curve was constructed for each drug. The longest analgesic effect was obtained for doxepin and imipramine. Although low doses of amitriptyline showed the same activity than doxepin, higher doses failed to reach the same effect. Selective inhibitors of serotonin showed no action at all doses tested. In the chronic sciatic nerve constriction injury model, doxepin and, to a smaller degree, amitriptyline and imipramine protected from allodynia; bupivacaine was ineffective. The antiallodynic effect always lasted less long than the analgesic effect. These observations provide support for the potential use of TCA as durable analgesics. Doxepin overall showed the most outstanding results in pain relief.

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A Study on Electrocardiographic Changes Secondary to the Use of Tricyclic Antidepressants in Patients with Chronic Pain

Abstract: The chronic use of TACs proved to be safe and effective, and it did not show changes in cardiac conduction with clinical repercussion.

Cited by 9 publications

References 17 publications

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

Safety Implications of Low-Dose Amitriptyline in Neuropathic Pain

Analgesic and Antiallodynic Effects of Antidepressants after Infiltration into the Rat

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