VORTIOXETINE

brands

Class

• Neuroscience-based Nomenclature: serotonin multimodal (S-MM)
• Multimodal antidepressant

VORTIOXETINE commonly prescribed for

(Bold for FDA approved)

How VORTIOXETINE works

• Increases release of several different neurotransmitters (serotonin, norepinephrine, dopamine, glutamate, acetylcholine, and histamine) and reduces the release of GABA through 3 different modes of action

• Mode 1: blocks serotonin reuptake pump (serotonin transporter)

• Mode 2: binds to G-protein-linked receptors (full agonist at serotonin 1A receptors; partial agonist at serotonin 1B receptors, antagonist at serotonin 1D and serotonin 7 receptors)

• Mode 3: binds to ion-channel-linked receptors (antagonist at serotonin 3 receptors)

• Full agonist actions at presynaptic somatodendritic serotonin 1A autoreceptors may theoretically enhance serotonergic activity and contribute to antidepressant actions

• Full agonist actions at postsynaptic serotonin 1A receptors may theoretically diminish sexual dysfunction caused by serotonin reuptake inhibition

• Antagonist actions at serotonin 3 receptors may theoretically enhance noradrenergic, acetylcholinergic, and glutamatergic activity and contribute to antidepressant and procognitive actions

• Antagonist actions at serotonin 3 receptors may theoretically reduce nausea and vomiting caused by serotonin reuptake inhibition

• Antagonist actions at serotonin 7 receptors may theoretically contribute to antidepressant and pro-cognitive actions as well as reduce insomnia caused by serotonin reuptake inhibition

• Partial agonist actions at serotonin 1B receptors may enhance not only serotonin release, but also acetylcholine and histamine release

• Antagonist actions at serotonin 1D receptors may enhance serotonin release

How long until VORTIOXETINE 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 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

• Sexual dysfunction

Life Threatening Side Effects

• Rare seizures

• Rare induction of mania and activation of suicidal ideation

weight gain

unusual

sedation

unusual

What to do about VORTIOXETINE side effects

• Wait

• Wait

• Wait

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

usual dosage range

• 5–20 mg/day

Dosage Forms

• Tablet 5 mg, 10 mg, 20 mg

long term use

• Long-term treatment of major depressive disorder is generally necessary

habit forming

• No

Renal Impairment

• No dose adjustment necessary

Hepatic Impairment

• No dose adjustment necessary for mild to moderate impairment

• Has not been studied in patien

Cardiac Impairment

• Not systematically evaluated in patients with cardiac impairment

• Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood

Elderly

• No dose adjustment necessary

• Some patients may tolerate lower doses better

• Risk of SIADH with SSRIs is higher in the elderly

• Reduction in the 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

• 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

• National Pregnancy Registry for Antidepressants: 1–844–405–6185

Breast Feeding

• Unknown if vortioxetine 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 non-treatment to both the infant and the mother

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