Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial.
Study Goal
The researchers aimed to determine whether melatonin alone or combined with amitriptyline improves the endogenous pain-modulating system and clinical symptoms (pain, pain threshold, sleep quality) in fibromyalgia patients compared to amitriptyline alone.
Results Summary
Melatonin alone or combined with amitriptyline significantly reduced pain (VAS scores) and improved the inhibitory pain-modulating system (NPS reduction during CPM-TASK) compared to amitriptyline alone. The combination showed marginal additional benefits in Fibromyalgia Impact Questionnaire (FIQ) and pressure pain threshold (PPT) improvements.
Population
63 females aged 18-65 with fibromyalgia.
Effective Dosage
10 mg melatonin at bedtime, alone or with 25 mg amitriptyline.
Duration
6 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin alone or in combination with amitriptyline | decrease | pain on the VAS | sixty-three females, aged 18 to 65 | 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 | reduced significantly | #1 |
melatonin alone | increase | the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK | sixty-three females, aged 18 to 65 | -2.65 (1.68) | increased | #2 |
melatonin in combination with amitriptyline | increase | the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK | sixty-three females, aged 18 to 65 | -2.4 (2.04) | increased | #3 |
amitriptyline alone | increase | the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK | sixty-three females, aged 18 to 65 | -1.04 (2.06) | - | #4 |
melatonin + amitriptyline | increase | FIQ and PPT improvement | sixty-three females, aged 18 to 65 | - | displayed better results | #5 |
melatonin | increase | the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK | sixty-three females, aged 18 to 65 | - | increased | #6 |
melatonin alone or associated with amitriptyline | decrease | pain on the VAS | sixty-three females, aged 18 to 65 | - | was better than amitriptyline alone in improving | #7 |
melatonin association with amitriptyline | increase | FIQ and PPT | sixty-three females, aged 18 to 65 | - | produced only marginal additional clinical effects | #8 |
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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 trials.gov upon under number NCT02041455. Registered January 16, 2014.