The incidence of cardiovascular and anticholinergic side effects was significantly lower compared to TCAs as a controlled study with over 3,300 patients revealed. Elevation of liver enzymes without signs of symptomatic liver disease has been infrequent. Mood swing to mania has also been seen and dictates termination of treatment. In psychotic patients emergence of delirium has been noticed. Milnacipran has a low incidence of sedation but improves sleep (both duration and quality) in depressed patients. In agitated patients or those with suicidal thoughts additive sedative/anxiolytic treatment is usually indicated. Interactions
MAOIs — hyperserotonergia (serotonin syndrome), potentially lethal hypertensive crisis
5-HT1 receptor agonists — coronary vasoconstriction with risk of angina pectoris and myocardial infarction
Epinephrine, norepinephrine (also in local anesthesia) — hypertensive crisis and/or possible cardiac arrhythmia
Clonidine — antihypertensive action of clonidine may be antagonized
Digitalis — hemodynamic actions increased
Triptans — there have been rare postmarketing reports of hyperserotonergia (serotonin syndrome). If concomitant treatment of milnacipran with a triptan is clinically warranted, careful observation of patient is advised when starting or increasing dosages. Alcohol — no interactions known; however, because milnacipran can cause mild elevation of liver enzymes, caution is recommended; the FDA advises against the concomitant use of alcohol and milnacipran

Pharmacology
Pharmacodynamics
Milnacipran inhibits the reuptake of serotonin and norepinephrine in an approximately 1:3 ratio, respectively.
Milnacipran was associated with increased adverse events when discontinuing use of the drug. Social anxiety
There is some evidence that milnacipran may be effective for social anxiety. Contraindications
Administration of milnacipran should be avoided in individuals with the following:

Known hypersensitivity to milnacipran (absolute contraindication)
Patients under 15 years of age (no sufficient clinical data)
Concomitant treatment with irreversible MAO inhibitors (e.g. tranylcypromine (Parnate), phenelzine (Nardil), >10 mg selegiline) or digitalis glycosides is an absolute contraindication.Administration of milnacipran should be done with caution in individuals with the following:

Concomitant treatment with parenteral epinephrine, norepinephrine, with clonidine, reversible MAO-A Inhibitors (such as moclobemide, toloxatone) or 5-HT1D-agonists (e.g. triptan migraine drugs)
Advanced renal disease (decreased dosage required)
Hypertrophy of the prostate gland (possibly urination hesitancy induced), with hypertension and heart disease (tachycardia may be a problem) as well as with open angle glaucoma.Milnacipran should not be used during pregnancy because it may cross the placenta barrier and no clinical data exists on harmful effects in humans and animal studies. Milnacipran is contraindicated during lactation because it is excreted in the milk, and it is not known if it is harmful to the newborn. Side effects
The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhydrosis, vomiting, palpitations, heart rate increase, dry mouth, and hypertension [FDA Savella prescribing information]. Milnacipran can have a significant impact on sexual functions, including both a decrease in sexual desire and ability. Milnacipran can cause pain of the testicles in men.