Text Size :
A A A

Milnacipran

Brands and Forms

  • Savella
    • tablet: 12.5mg, 25mg, 50mg, 100mg.
  • Toledomin
  • Ixel

Uses of Milnacipran

Milnacipran is used for treating Depressive Disorders, chronic pain, neuropathic pain, and Fibromyalgia.

How Milnacipran Works

Milnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI). It boosts the actions of serotonin and norepinephrine in the central nervous system, and has similar effects on dopamine. At high doses it is also a weak noncompetitive NMDA-receptor antagonist.

Cautions when Using Milnacipran

Milnacipran can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Children and adolescents who use antidepressants like Milnacipran may develop self-injurious or suicidal behaviors (for more information, see here).

Use with caution in people with a known seizure disorder, glaucoma, and in those who are taking anticoagulant (blood thinning) medication.

Long-term use of Milnacipran may be associated with increased risk of osteoporosis and bone fractures in individuals over age 50.

Milnacipran should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.

Dosing of Milnacipran

Start on day 1 with a single 12.5mg dose. On days 2 and 3 give 12.5mg twice daily. On days 4-7 give 25mg twice daily. After day 7, give 50mg twice daily. At that point, it is recommended to wait about 4 weeks for a therapeutic effect to occur before deciding to increase the dose further. Usually, the maximum recommended dose is 100mg twice a day, but in some cases doses of up to 150mg twice a day can be used.

When wanting to stop this medication, the dose should be decreased gradually over a period of 6-8 weeks. A sudden cessation of the medication can result in a discontinuation syndrome.

Onset of action

Therapeutic effects are not expected before 2-4 weeks at a dose of 50mg twice a day. If no significant effects are seen after 6-8 weeks of use, including at least 2 weeks at a dose above 50mg twice a day, then the medication may not work at all.

Kidney impairment

No dose adjustment is required for people with mild kidney function impairment. Use with caution in moderate kidney function impairment. For patients with severe kidney function impairment (CrCl 5-29mL/min), reduce dose by 50% of usual. Use is not recommended for patients with end-stage renal disease.

Liver impairment

Use with caution in individuals with liver impairment.

Side-effects of Milnacipran

Below is a list of most of the reported side-effects of Milnacipran. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: hot flushes; palpitations; elevated blood pressure.

Central Nervous System: headache; dizziness; insomnia; paresthesia; decreased libido (see below on managing sexual side-effects); tremor; fatigue; extrapyramidal symptoms (rare); seizures (rare); serotonin syndrome (rare).

Dermatologic: excessive sweating; itchiness; rash; hair loss (rare).

Endocrine/Metabolism: elevated prolactin (rare), SIADH (rare).

Eyes, Ears, Nose and Throat: blurred vision; accommodation difficulties.

Gastrointestinal: nausea; dry mouth; constipation; diarrhea; vomiting; dyspepsia; loose stools; flatulence; appetite loss; weight loss or gain; esophageal reflux.

Genitourinary: decreased urine flow in men; ejaculation disorder (see below on managing sexual side-effects); erectile dysfunction; abnormal orgasm; impotence; testicular pain; urinary retention; prostatitis.

Hematologic: increases bleeding time (thins the blood); easy bruising; thrombocytopenia.

Muskuloskeletal: joint and muscle pain; risk of osteoporosis and bone fractures with long-term use.

Psychiatric: anxiety; agitation; apathy; worsening depression; suicidal thoughts (overall, Milnacipran use helps to lower risk of suicide); self-injurious behaviors among children and adolescents; can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder; can induce psychosis in people with Psychotic Disorders or Bipolar Disorder.

Respiratory: upper respiratory tract infection; shortness of breath.

Common side-effects of Milnacipran

Nausea, constipation, headache, insomnia, dizziness, hot flushes, excessive sweating, sexual dysfunction (about 5%, see below on managing sexual side-effects).

Rare but serious side-effects of note of Milnacipran

  • Children and adolescents who use antidepressants like Milnacipran may develop self-injurious or suicidal behaviors (for more information, see here).
  • Seizures

Milnacipran discontinuation syndrome

Individuals who suddenly stop using Milnacipran after taking the medication at moderate or high doses over a significant period of time are at risk of developing a discontinuation syndrome, which can include the following symptoms: dizziness, electric shock-like sensations, sweating, nausea, insomnia, tremor, anxiety, restlessness, agitation, depressed mood, irritability, confusion, lethargy, and vertigo. These symptoms usually start anywhere from one day to one week after the medication was stopped, and can persists for days or even weeks.

This syndrome can be treated by restarting the medication at its prior dose. It can be prevented by decreasing the dose gradually over a period of 6-8 weeks when wanting to stop the medication. In rare cases, individuals may experience the discontinuation syndrome even when the medication is being tapered gradually; in such cases, an extremely slow and gradual taper will be necessary.

Managing sexual side-effects of Milnacipran

The first step to manage this is to try to lower the dose of the Milnacipran. If this is not possible, or is not an effective solution, then either Bupropion, or Sildenafil (Viagra) or Vardenafil (Levitra), can be added [ref]. (Sildenafil and Vardenafil can be effective for female sexual side-effects as well, including difficulty achieving orgasm [ref, ref]). Caution should be used when combining Milnacipran with Bupropion, as elevations in blood pressure could result.

Bupropion and Mirtazepine are two antidepressants that tend to have very low rates of sexual side-effects.

Milnacipran overdose

Vomiting, dizziness, increased blood pressure, increased hepatic enzymes, confusion, changes in levels of consciousness (ranging from somnolence to coma), serotonin syndrome, cardiorespiratory arrest.

Milnacipran and pregnancy

Category C: some animal studies show adverse effects at very high doses, but no controlled human studies have been done; should only be used in pregnancy if clearly needed and if benefits outweigh potential risks. For further information, see the section on treating Depression in pregnancy.

Medical Monitoring for Milnacipran

Blood pressure should be measured a few weeks after starting the medication and after dose increases.

Drug Interactions with Milnacipran

  • Caution should be used when combining Milnacipran with other medications that can increase bleeding time and reduce blood clotting, including Aspirin, NSAIDs, anti-platelet agents, Heparin and Coumadin.
  • Using caution when combining Milnacipran with adrenergic medications like stimulants, because it inhibits norepinephrine reuptake and significant hypertension or cardiac arrhythmias could occur.
  • Combination with other serotonergic medications, including SSRI antidepressants, could potentially precipitate a serotonin syndrome.
  • Individuals who consume large amounts of alcohol regularly can experience hepatotoxicity when using Milnacipran.
  • Because Milnacipran inhibits norepinephrine reuptake, the antihypertensive effect of Clonidine may be decreased.
  • Avoid combining Milnacipran with IV Digoxin, as hemodynamic effects may be potentiated, resulting in hypotension and tachycardia.
  • Milnacipran should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.