Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders (worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy)(monotherapy in patients with bipolar disorder should be avoided). Milnacipran is not FDA approved for the treatment of major depressive disorder, bipolar disorder or for use in children. May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin or NSAIDs due to ulcerogenic potential. May increase blood pressure and heart rate (consider dose reduction or gradual discontinuation of therapy in individuals with sustained hypertension or tachycardia during therapy). Cases of increased liver enzymes and severe liver injury including fulminant hepatitis have been reported (avoid use in patients with substantial ethanol intake, evidence of chronic liver disease or hepatic impairment; discontinue therapy with the presentation of jaundice or other signs of hepatic dysfunction and do not reinitiate therapy unless another source or cause is identified). Serotonin Syndrome (SS)/Neuroleptic Malignant Syndrome (NMS)-like reactions have occurred with Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) and Selective Serotonin Reuptake Inhibitors (SSRIs) when used alone, and particularly when used in combination with serotonergic agents (e.g. triptans) or antidopaminergic agents (e.g. antipsychotics)(discontinue treatment and any concomitant serotonergic and/or antidopaminergic agents immediately if signs/symptoms arise). SIADH and hyponatremia have been reported predominantly in the elderly. Milnacipran may cause increased urinary resistance and increased risk of mydriasis in patients with controlled narrow-angle glaucoma. Use caution with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism. May cause withdrawal syndrome (to discontinue therapy with milnacipran, gradually taper dose). It has been suggested that vasoconstrictors should be administered with caution and vital signs monitored in dental patients taking antidepressants that affect norepinephrine. Male patients with a history of obstructive uropathies may experience higher rates of genitourinary adverse events.