brands

Class

• Neuroscience-based Nomenclature: serotonin, norepinephrine reuptake inhibitor (SN-RI)
• SNRI (dual serotonin and norepinephrine reuptake inhibitor); antidepressant; chronic pain treatment

MILNACIPRAN commonly prescribed for

(Bold for FDA approved)

How MILNACIPRAN works

• Boosts neurotransmitters serotonin, norepinephrine, and dopamine

• Blocks serotonin reuptake pump (serotonin transporter), presumably increasing serotonergic neurotransmission

• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission

• Presumably desensitizes both serotonin 1A receptors and beta adrenergic receptors

• Weak noncompetitive NMDA receptor antagonist (high doses), which may contribute to actions in chronic pain

• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, milnacipran can increase dopamine neurotransmission in this part of the brain

How long until MILNACIPRAN works

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

• If it is not working within 6–8 weeks, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of symptoms in depression

Notable Side Effects

• Most side effects increase with higher doses, at least transiently

• Headache, nervousness, insomnia, sedation

• Nausea, diarrhea, decreased appetite

• Sexual dysfunction (abnormal ejaculation/ orgasm, impotence)

• Asthenia, sweating

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• Dose-dependent increased blood pressure

• Dry mouth, constipation

• Dysuria, urological complaints, urinary hesitancy, urinary retention

• Increase in heart rate

• Palpitations

Life Threatening Side Effects

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

• Rare seizures

weight gain

unusual

sedation

not usual

What to do about MILNACIPRAN side effects

Wait

• Wait

• Wait

• Lower the dose

• In a few weeks, switch or add other drugs

usual dosage range

• 30–200 mg/day in 2 doses

Dosage Forms

• Capsule 25 mg, 50 mg (France, other European countries, and worldwide markets)

• Capsule 15 mg, 25 mg, 50 mg (Japan)

• Tablet 12.5 mg, 25 mg, 50 mg, 100 mg

long term use

• Safe

habit forming

• No

Renal Impairment

• Use caution for moderate impairment

• For severe impairment, 50 mg/day; can increase to 100 mg/day if needed

• Not recommended for patients with endstage renal disease

Hepatic Impairment

• No dose adjustment necessary

• Not recommended for use in chronic liver disease

Cardiac Impairment

• Drug should be used with caution

Elderly

• Some patients may tolerate lower doses better

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/ or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Not well studied

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Not generally recommended for use during pregnancy, especially during first trimester

• Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding