Levomilnacipran (brand name Fetzima) is an antidepressant which was approved in the United States in 2013 for the treatment of major depressive disorder (MDD) in adults. It is the levorotatory enantiomer of milnacipran, and has similar effects and pharmacology, acting as a serotonin–norepinephrine reuptake inhibitor (SNRI). Medical uses
Depression
The FDA approved levomilnacipran for the treatment of major depressive disorder based on the results of one 10-week phase II and four 8-week phase III clinical trials. Four of the five trials demonstrated a statistically significant superiority to placebo as measured by the Montgomery–Åsberg Depression Rating Scale. Superiority to placebo was also demonstrated by improvement in the Sheehan Disability Scale. Side effects
Side effects seen more often with levomilnacipran than with placebo in clinical trials included nausea, dizziness, sweating, constipation, insomnia, increased heart rate and blood pressure, urinary hesitancy, erectile dysfunction and delayed ejaculation in males, vomiting, tachycardia, and palpitations. Pharmacology
Pharmacodynamics
Relative to other SNRIs, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine. To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 14:1, milnacipran = 1.6:1, and levomilnacipran = 1:2. The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear, but may include improved effectiveness, though also increased side effects.Levomilnacipran is selective for the serotonin and norepinephrine transporters, lacking significant affinity for over 23 off-target sites.
Hypertrophic osteoarthropathy is a medical condition combining clubbing and periostitis of the small hand joints, especially the distal interphalangeal joints and the metacarpophalangeal joints. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen. The condition may occur alone (primary), or it may be secondary to diseases like lung cancer. Among patients with lung cancer, it is most associated with adenocarcinoma and least associated with small cell lung cancer. These patients often get clubbing and increased bone deposition on long bones. Their presenting signs and symptoms are sometimes only clubbing and painful ankles. Cause
Hypertrophic osteoarthropathy is one of many distant effect disorders due to cancer, with lung cancer being the most common cause but also occurring with ovarian or adrenal malignancies. A distant effect disorder, or a paraneoplastic syndrome, affects distant areas and thus is not related to local compression or obstruction effects from the tumor. Other paraneoplastic syndromes include hypercalcemia, SIADH, Cushings syndrome and a variety of neurological disorders. Thought to be due to fibrovascular proliferation caused by accumulation of megakaryocytes in the digital vessels which are normally filtered by the lungs. Diagnosis
People with hypertrophic osteoarthropathy may have bone scans showing parallel lines of activity along the cortex of the shafts and ends of tibiae, femurs and radii; especially around the knees, ankles and wrists. This activity may decrease after treatment of the underlying cause. Treatment
Non-steroidal anti-inflammatory drugs (NSAIDs) can give significant relief of the symptoms.