Preoperative Anxiolytic Effect of Melatonin and Clonidine on Postoperative Pain and Morphine Consumption in Patients Undergoing Abdominal Hysterectomy: A Double-Blind, Randomized, Placebo-Controlled Study

Anesthesia Service and Perioperative Medicine, Hospital de CLíNICAS DE Porto Alegre/Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The journal of pain: official journal of the American Pain Society (Impact Factor: 4.01). 12/2008; 10(1):100-8. DOI: 10.1016/j.jpain.2008.08.007
Source: PubMed


Recent evidence has demonstrated analgesic, anti-inflammatory, and anxiolytic properties of melatonin. Taking into account that higher anxiety makes the control of postoperative pain more difficult, one can hypothesize that melatonin anxiolytic and analgesic effects improve the control of postoperative pain. Thus, we conducted a randomized, double-blind, placebo-controlled study with 59 patients undergoing abdominal hysterectomy to test the hypothesis that melatonin is as effective as clonidine and that both are more effective than placebo in reducing postoperative pain. Additionally, we compared their anxiolytic effects on postoperative pain. Patients were randomly assigned to receive oral melatonin (5 mg) (n = 20), clonidine (100 microg) (n = 19), or placebo (n = 20) orally. In addition to primary outcomes of pain intensity and analgesic consumption, secondary outcome measures included postoperative state anxiety. In anxious patients 6 hours after surgery, the number of patients needed to be to prevent moderate to intense pain during the first 24 hours after surgery was 1.52 (95% CI, 1.14 to 6.02) and 1.64 (95% CI, 1.29 to 5.93), respectively, in the melatonin and clonidine groups compared with placebo. Also, the anxiolytic effect of melatonin and clonidine resulted in reduced postoperative morphine consumption by more than 30%. However, in the mildly anxious, it was not observed the treatment effect on pain. PERSPECTIVES: The preoperative anxiolysis with melatonin or clonidine reduced postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy. The effects these 2 drugs were equivalent and greater than with placebo.

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Available from: Rosa Levandovski, Jun 24, 2014
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    • "Melatonin’s effect on pain has been demonstrated in animals for inflammatory [8] and neuropathic pain [11-13], as well in acute [10,14] and chronic pain in humans [15,16]. In addition, there is some clinical evidence of melatonin’s effect on FM [5,6]. "
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    ABSTRACT: Central disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality. Sixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment. Melatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P < 0.01). The delta values on the VAS scores were-12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin and melatonin+amitriptyline groups, respectively. Melatonin alone and in combination increased the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,-2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin + amitriptyline treated displayed better results than melatonin and amitriptyline alone in terms of FIQ and PPT improvement (P < 0.05, fort both). Melatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT. Trial registration Current controlled trail is registered at clinical upon under number NCT02041455. Registered January 16, 2014.
    BMC pharmacology & toxicology 07/2014; 15(1):40. DOI:10.1186/2050-6511-15-40
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    • "As an anxiolytic agent, MT has proven to be effective in preclinical studies as well as in humans (Caumo et al., 2009; Crupi et al., 2010; Papp et al., 2006; Srinivasan et al., 2006; Tian et al., 2010). Clinically, it has been successfully used to facilitate the discontinuation of benzodiazepine therapy in patients with insomnia (Garfinkel et al., 1999) and to reduce the anxiety scores in cataract surgery patients (Khezri and Merate, 2013). "
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    ABSTRACT: In spite the wide variety of drugs available for treating anxiety, this disorder continues to represent a worldwide health problem that is classified within the first 10 causes of disability. Therefore, the search continues for new antianxiety agents, particularly those not related to benzodiazepines. Even though melatonin has been prescribed as an anxiolytic drug, its use is currently limited due to its short half-life and photo-sensitivity, among other disadvantages. The present study explores the antianxiety properties of a new 1-N substituted melatonin analogue, M3C, in pinealectomized rats submitted to two behavioral tests (the cumulative burying behavior paradigm and the elevated plus-maze). Results from both tests show that M3C is effective as an anxiolytic-like agent, at doses lower than any other melatonin analogue previously reported. The blocking of these actions by luzindole together with the available data suggests that the anxiolytic properties of M3C are mediated by MT1 and MT2 receptors.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2014; 51. DOI:10.1016/j.pnpbp.2014.01.015 · 3.69 Impact Factor
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    • "? + + + Caumo et al. 2009 [5] + + + + + ? + + + Evagelidis et al. 2009 [30] + + + + ? "
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    ABSTRACT: We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction; and safety. Compared with placebo, melatonin reduced the standardised mean difference (95% CI) pre-operative anxiety score by 0.88 (0.44-1.33) and postoperative pain score by 1.06 (0.23-1.88). The magnitude of effect was unreliable due to substantial statistical heterogeneity, with I(2) 87% and 94%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements.
    Anaesthesia 05/2014; 69(10). DOI:10.1111/anae.12717 · 3.38 Impact Factor
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