Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia : A 13-week Randomized, Placebo Controlled Cross Over Trial

Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia: A 13-week Randomized, Placebo Controlled Cross Over Trial

This study was designed to investigate whether milnacipran is safe and effective in improving cognitive function in fibromyalgia. In addition, this study was aimed to investigate whether improvement in neurocognitive status due to milnacipran correlates with improvements in pain, to investigate whether improvement in neurocognitive status due to milnacipran correlates with improvements in fatigue, and to determine whether treatment with improvement in neurocognitive status, pain and fatigue correlates with functional improvement.

Cognitive dysfunction is observed in fibromyalgia, especially for episodic memory, learning, and working memory.There is evidence for dysregulation of the attention system from low-level sensory processes up to emotional processes, and increased sensitivity to distraction.Milnacipran's balance of norepinephrine (NE) to serotonin (5-HT) of 3:1, similar to amitriptyline, a tricyclic that has demonstrated efficacy in fibromyalgia, as compared to venlafaxine which is 1:30, or duloxetine which is 1:10.7 In addition, because of milnacipran's effect on 5-HT, it should also be effective in treating other symptoms such as sleep disturbances and mood changes, which are associated to fibromyalgia, as well as other functional somatic syndromes. It is worth noting that several medications to treat fibromyalgia are sedating (e.g pregabalin, opioids, muscle relaxants) and impair neurocognition.

Inclusion Criteria:

• Age 18 to 65 years.
• Specific diagnosis of FM by the participant's rheumatologist or physician, including written confirmation, from a physician, of the FM diagnosis.
• Confirmation of the FM diagnosis by American College of Rheumatology Criteria and a physical tender point examination.
• Ability to give informed consent.
• If female, nonpregnant/nonlactating.
• If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation) during the trial.

Exclusion Criteria:

• Bipolar disorders, any psychotic disorder.
• the existence of concomitant rheumatological disorders, including rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's disease, Sjogren's syndrome or scleroderma.
• Substance dependence (except nicotine dependence) in the previous 3 months.
• Currently suicidal or high suicide risk.
• Serious or unstable medical disorders.
• Any psychotropic drug treatment in the previous 2 weeks before screening.
• A positive urine pregnancy test.
• Screening laboratory values three times the limits of normal or judged clinically significant by the investigator.
• History of hypersensitivity to milnacipran.
• Seizure disorder, traumatic brain injury, any CNS disorder that affects cognitive status.
• Concomitant meds: A minimum of 30 days on stable dose of analgesics and a minimum of 4 week washout from antidepressants and fibromyalgia specific medication ( e.g. pregabalin, neurontin) and supplements ( St John's wort, SAM-E).
• Narrow angle glaucoma.