LEVOMILNACIPRAN

brands

Class

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

LEVOMILNACIPRAN commonly prescribed for

(Bold for FDA approved)

How LEVOMILNACIPRAN works

• Boosts neurotransmitters serotonin, norepinephrine, and dopamine

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

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

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

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

How long until LEVOMILNACIPRAN works

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

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

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

Notable Side Effects

• Nausea, vomiting, constipation

• Hyperhidrosis

• Tachycardia, heart rate increase, palpitations

• Erectile dysfunction

• Urinary hesitancy or retention

Life Threatening Side Effects

• Rare seizures

• Rare induction of mania and activation of suicidal ideation

weight gain

unusual

sedation

not usual

What to do about LEVOMILNACIPRAN side effects

• Wait

• Wait

• Wait

• Lower the dose

• In a few weeks, switch to another agent or add other drugs

usual dosage range

• 40–120 mg once daily

Dosage Forms

• Extended-release capsule 20 mg, 40 mg, 80 mg, 120 mg

long term use

• Has not been evaluated in controlled studies, but long-term treatment of major depressive disorder is generally necessary

habit forming

• No

Renal Impairment

• Maximum dose 80 mg once daily for moderate impairment

• Maximum dose 40 mg once daily for severe impairment

Hepatic Impairment

• Dose adjustment not necessary

Cardiac Impairment

• Not systematically evaluated in patients with cardiac impairment

• Drug should be used with caution

Elderly

• Some patients may tolerate lower doses better

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

Children and Adolescents

• Safety and efficacy have not been established

• 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 strongly consider informing parents or guardian of this risk so they can help observe child or adolescent patients

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

• At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn

• 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

• Exposure to serotonin reuptake inhibitors early in pregnancy may be associated with increased risk of septal heart defects (absolute risk is small)

• Use of serotonin reuptake inhibitors beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven

• Exposure to serotonin reuptake inhibitors late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia

• 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

• Unknown if levomilnacipran is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• 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