Milnacipran

Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia.

Probable Serotonin Syndrome and Withdrawal Symptoms Caused by Milnacipran.[Pubmed:27904101]

Yakugaku Zasshi. 2016;136(12):1675-1679.

A 70-year-old woman, residing in a nursing home, was admitted to our hospital because of cerebral hemorrhage. She had excessive sweating, a temperature above 37 degrees C, and intermittent muscle spasm such as myoclonus, since the time of admission. We suspected that these symptoms were related to side effects caused by the Milnacipran she was taking for depression, prior to hospitalization. After we discontinued Milnacipran, the patient began exhibiting withdrawal symptoms such as excitement and insomnia. When we substituted Milnacipran with mianserin, the withdrawal symptoms diminished and the excessive sweating and involuntary movement disappeared. Serotonin-norepinephrine reuptake inhibitor (SNRI) and selective serotonin reuptake inhibitor (SSRI) have been widely utilized in the clinic to treat depression; serious side effects such as serotonin syndrome and withdrawal syndrome associated with their discontinuation, have been reported. However, it is unlikely that serotonin syndrome and withdrawal syndrome due to a precedent use of Milnacipran would have been reported. This case was suspected to be related to serotonin syndrome and withdrawal syndrome from the course of treatment. This case provides valuable information for addressing new similar cases caused by Milnacipran.

Influence of the selective antagonist of the NR2B subunit of the NMDA receptor, traxoprodil, on the antidepressant-like activity of desipramine, paroxetine, milnacipran, and bupropion in mice.[Pubmed:27900470]

J Neural Transm (Vienna). 2017 Mar;124(3):387-396.

Pre-clinical and clinical studies indicated that a blockade of the NMDA receptor complex creates new opportunities for the treatment of affective disorders, including depression. The aim of the present study was to assess the influence of traxoprodil (10 mg/kg) on the activity of desipramine (10 mg/kg), paroxetine (0.5 mg/kg), Milnacipran (1.25 mg/kg), and bupropion (10 mg/kg), each at sub-therapeutic doses. Moreover, brain levels of traxoprodil and tested agents were determined using HPLC. The obtained results were used to ascertain the nature of occurring interaction between traxoprodil and studied antidepressants. The experiment was carried out on naive adult male Albino Swiss mice. Traxoprodil and other tested drugs were administered intraperitoneally. The influence of traxoprodil on the activity of selected antidepressants was evaluated in forced swim test (FST). Locomotor activity was estimated to exclude false positive/negative data. To assess the influence of traxoprodil on the concentration of used antidepressants, their levels were determined in murine brains using HPLC. Results indicated that traxoprodil potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity. Only in the case of co-administration of traxoprodil and bupropion, increased bupropion concentrations in brain tissue were observed. All tested agents increased the traxoprodil levels in the brain. Administration of a sub-active dose of traxoprodil with antidepressants from different chemical groups, which act via enhancing monoaminergic transduction, caused the antidepressant-like effect in FST in mice. The interactions of traxoprodil with desipramine, paroxetine, Milnacipran, and bupropion occur, at least partially, in the pharmacokinetic phase.

No evidence of potentiation of buprenorphine by milnacipran in healthy subjects using a nociceptive test battery.[Pubmed:27651026]

Eur J Pain. 2017 Mar;21(3):494-506.

BACKGROUND: Serotonin-norepinephrine reuptake inhibitors inhibit the reuptake of serotonin and noradrenalin and are used in the treatment of neuropathic pain. Animal studies suggest that Milnacipran co-administered with opioids may potentiate the analgesic effect of mu-opioid receptor agonists. This study hypothesized that co-administration of Milnacipran and buprenorphine would have a synergistic effect in evoked pain models in healthy subjects. METHODS: This was a randomized double-blinded, placebo-controlled, four-way cross-over, multiple dose clinical trial to investigate the analgesic effects of buprenorphine (placebo, 0.5, 1 and 3 mug/kg) in combination with Milnacipran (placebo, 25 and 50 mg) in healthy subjects. RESULTS: 11 healthy men were enrolled in the study. Buprenorphine alone showed a dose-response relationship indicative of anti-nociception in the pain tests. Following Milnacipran administration, no changes were seen in the pharmacodynamic measurements for pain, psychomotor function, body stability or eye movements. For the electrical tests, cold pressor test and pressure pain test, buprenorphine alone was superior when compared with buprenorphine plus Milnacipran. No differences in pharmacodynamic variables, besides an increase in pupil/iris ratio, were observed after repeated administration of Milnacipran 50 mg. Single and multiple doses of 25 or 50 mg Milnacipran did not further potentiate the anti-nociceptive effects of buprenorphine. CONCLUSIONS: Buprenorphine showed dose-dependent effects consistent with its pharmacological profile. Milnacipran alone did not affect any of the pain variables. The combination of both buprenorphine and Milnacipran did not potentiate or show a synergistic effect on the pain models used in this study. SIGNIFICANCE: Buprenorphine is known to be a potent opioid agonist. Animal studies suggest that Milnacipran co-administered with opioids may potentiate the analgesic effect of mu-opioid receptor agonists. Here, we found that buprenorphine showed a dose-dependent analgesic effect, but that no potentiation or synergy on a battery of evoked pain tasks could be observed after co-administration of both Milnacipran and buprenorphine.

Psychiatric comorbidities and use of milnacipran in patients with chronic dizziness.[Pubmed:27392838]

J Vestib Res. 2016 Jul 2;26(3):335-40.

BACKGROUND: Psychiatric comorbidities are an important issue in the treatment of chronic dizziness patients. OBJECTIVE: To test the correlation between psychiatric status and subjective handicaps and to examine the effects of Milnacipran on handicaps. METHODS: Hospital anxiety and depression scale (HADS) and handicaps were assessed by a questionnaire before and eight weeks after Milnacipran treatment (50 mg/day) in 29 consecutive patients with chronic dizziness. Effects of milnaciplan were compared with fluvoxamine (200 mg/day). RESULTS: A significant correlation was found between anxious and depressive scale scores and also between HADS and handicaps. Duration of symptoms was longer in the anxious/depressive group (HADS>==13) than in the non-anxious/depressive group. Handicaps and HADS were significantly decreased after treatment only in the anxious/depressive group. There were no overall differences in drug effects between milnaciplan and fluvoxamine. However, the rate of patients with a post/pre ratio of handicaps <80% was higher in milnaciplan group compared with the fluvoxamine group. CONCLUSIONS: Not only anxiety disorders but also depression should be considered as comorbid psychiatric disorders in patients with chronic dizziness. Dizzy patients with psychiatric comorbidities have a longer duration of symptoms and more handicaps than those without psychiatric disorders. Milnacipran may be chosen as a treatment for patients with chronic dizziness with comorbid psychiatric disorders in case of and insufficient response to SSRIs.