Use Alternate Drug. Strong CYP3A4 inhibitors may increase vilazodone plasma levels by 50% - Reduce daily dose to 20 mg.tramadolSerious - Use Alternative (1)tramadol, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated.tranylcypromineContraindicated (1)tranylcypromine, vilazodone. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration with MAO-A inhibitors are contraindicated. Do not prescribe vilazodone within 14 days of discontinuing or starting an MAO inhibitor.trazodoneSerious - Use Alternative (1)trazodone, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated.trifluoperazineMonitor Closely (1)vilazodone, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.venlafaxineSerious - Use Alternative (1)venlafaxine, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .verapamilSerious - Use Alternative (1)verapamil increases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If intolerable adverse effects occur when coadministered with moderate CYP3A4 inhibitors, reduce daily dose to 20 mg.voriconazoleSerious - Use Alternative (1)voriconazole increases toxicity of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase vilazodone plasma levels by 50% - Reduce daily dose to 20 mg.vortioxetineSerious - Use Alternative (1)vilazodone, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.warfarinMonitor Closely (1)vilazodone, warfarin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serotonin release by platelets plays an important role in hemostasis. SSRIs and SNRIs may increase anticoagulation effect of warfarin. .zafirlukastMonitor Closely (1)vilazodone increases levels of zafirlukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dose adjustment needed with mild CYP3A4 inhibitors.ziprasidoneMonitor Closely (1)vilazodone, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zolmitriptanSerious - Use Alternative (1)zolmitriptan, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. . >10% Diarrhea (28%) Nausea (23%) 1-10% Dizziness (9%) Xerostomia (8%) Insomnia (6%) Vomiting (5%) Fatigue (4%) Abnormal dreams (4%) Libido decreased (4%) Abnormal orgasm (3%) Dyspepsia (3%) Flatulence (3%) Gastroenteritis (3%) Somnolence (3%) Paresthesia (3%) Arthralgia (3%) Restlessness/akathisia (3%) Jittery sensation (2%) Tremor (2%) Delayed ejaculation (2%) Erectile dysfunction (2%) Increased appetite (2%) Postmarketing Reports General disorders and administrative site conditions: Irritability Psychiatric disorders: Hallucinations, suicide attempt, suicidal ideation Gastrointestinal disorders: Acute pancreatitis Nervous system disorders: Sleep paralysis Black Box Warnings Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders In children and young adults, the risks must be weighed against the benefits of taking antidepressants Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy, as well as during dosage adjustments The patient’s family should communicate any abrupt changes in behavior to the healthcare provider Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy May worsen psychosis in some patients or cause a shift to mania or hypomania in bipolar disorder; patients should be screened for bipolar disorder prior to the initiation of therapy Not approved for use in pediatric patientsContraindications Hypersensitivity Coadministration with serotonergic drugs Do not use MAOIs concomitantly or within 14 days before initiating vilazodone or within 14 days after discontinuing vilazodone Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma Starting vilazodone in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome If linezolid or IV methylene blue must be administered, discontinue vilazodone immediately and monitor for CNS toxicity; may resume vilazodone 2 weeks after last linezolid or methylene blue dose Cautions May precipitate mixed/manic episode if initiated for bipolar disorder May cause serotonin syndrome or neuroleptic malignant syndrome-like reactions, including agitation, hallucinations, coma, autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) Use with caution in patients with history of seizures; has not been systematically evaluated in patients with seizure disorders (caution advised) Serotonin reuptake inhibition may increase risk of bleeding (caution with drugs that inhibit platelets or coagulation) Decrease dose gradually when discontinuing, to avoid dysphoric mood, irritability, insomnia, agitation, and confusion CYP3A4 (major substrate); CYP2C19 (minor substrate, minor inhibitor, minor inducer); CYP2D6 (minor substrate, minor inhibitor); CYP2C8 (moderate inhibitor); increased plasma concentration (by 50%) observed when coadministered with strong CYP3A4 inhibitors (eg, ketoconazole) Highly bound to plasma proteins (administration to patient taking another drug that is highly protein bound may increase free concentrations of the other drug) Hyponatremia has been reported with other SSRIs, and SNRIs; common adverse effects include diarrhea, nausea, xerostomia, dizziness, and insomnia; can occur in association with syndrome of inappropriate antidiuretic hormone secretion (SIADH) Bone fractures reported with antidepressant treatment; consider possibility of fragility fracture if antidepressant treated patient presents with unexplained bone pain, swelling, point tenderness, or bruising; May cause sexual dysfunction MAOIs (see Contraindications) Coadministration with 5HT receptor agonist (ie, triptan), other serotonergic drugs (eg, SSRIs, SNRIs, buspirone, tramadol), or antidopaminergic drugs may increase risk for serotonin syndrome Concomitant use with serotonin precursors (eg, tryptophan) not recommended Serotonin reuptake inhibition may increase risk of bleeding (caution when coadministered with aspirin, NSAIDs, warfarin, and other anticoagulants) Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy There is conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (PPHN; see Pregnancy) Write prescription for smallest quantity consistent with good patient care Abrupt discontinuation or interruption of therapy associated with discontinuation syndrome; antidepressants with shorter half-lives, prolonged treatment, or abrupt discontinuation, associated with increased risk of developing discontinuation syndrome; for antidepressants of short of intermediate hslf-lives, symptoms may emerge within 2-5 days after treatment discontinuation; may last 7-14 days Sexual dysfunction Use of may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder Discuss potential management strategies to support patients in making informed decisions about treatment Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ There are no adequate and well-controlled studies in pregnant women; a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at beginning of pregnancy; women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants; consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum Exposure in late pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN); monitor neonates who were exposed to therapy in third trimester of pregnancy for PPHN and drug discontinuation syndrome Persistent pulmonary hypertension of the newborn Potential risk of PPHN when used during pregnancy Initial public health advisory in 2006 was based on a single published study; since then, there have been conflicting findings from new studies, making it unclear whether use of SSRIs during pregnancy can cause PPHN FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN FDA recommendation: FDA advises health-care professionals not to alter their current clinical practice of treating depression during pregnancy and to report any adverse events to the FDA MedWatch program Lactation There are no data on presence in human milk, effects on breastfed infant, or on milk production; however, drug is excreted in rat milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Mechanism of antidepressant effect is not fully understood, but may be related to serotonergic activity in the CNS through selective inhibition of serotonin reuptake; no effect on norepinephrine or dopamine reuptake Partial agonist of serotonergic 5-HT1A receptor whose activity may be altered in depression and anxiety Absorption Bioavailability: 72% (with food) Peak plasma time: 4-5 hr Peak plasma concentration: 156 ng/mL AUC: 1645 ng•h/mL Distribution Protein bound: 96-99% Metabolism Extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase); CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6 Elimination Half-life: 25 hr Excretion: Feces (2% unchanged), urine (1% unchanged) Instructions Take with food Administration in fasted state (without food) may decrease blood concentration (AUC) by up to 50% and may result in decreased effectiveness Discontinuing Gradually reduce dose rather than discontinue abruptly Taper from 40 mg/day to 20 mg/day for 4 days, followed by 10 mg/day7 for 3 days Patients taking 20 mg/day should be tapered to 10 mg/day for 7 days