selective serotonin reuptake inhibitors ssris
Treatment of major depressive disorder.
Selectively inhibits the reuptake of serotonin in the CNS. May also act as a 5–HT1Aagonist and as a 5–HT3 antagonist
Absorption: Well absorbed (75%) following oral administration.
Distribution: Extensive extravascular distribution
Protein Binding: 98%.
Metabolism and Excretion: Extensively metabolized, primarily by the CYP2D6 enzyme system, 59% excreted in urine as metabolites, 26% in feces as metabolites, minimal renal excretion of unchanged drug.
Half-life: 66 hr.
TIME/ACTION PROFILE (antidepressant effect)
|PO||1–2 wk||4–8 wk||unknown|
- Concurrent or recent MAOIs for psychiatric use, linezolid or IV methylene blue;
- OB: May cause fetal harm (third trimester use may result in respiratory distress, cyanosis, apnea, seizures, temperature instability feeding difficulties and behavioral issues infants, may also be associated with persistent pulmonary hypertension of the newborn [PPHN]).
Use Cautiously in:
- History of bipolar disorder (may activate mania/hypomania);
- History of suicide attempt/ideation
- Poor CYP2D6 metabolizers will have ↑ blood levels;
- Angle-closure glaucoma;
- Geri: ↑ risk of hyponatremia;
- Lactation: Use while breast feeding only if potential benefit justifies potential risk to the fetus;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
GI: constipation, nausea
F and E: hyponatremia
GU: sexual dysfunction
Misc: allergic reactions including angioedema, SEROTONIN SYNDROME
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent use of MAOIs for psychiatric conditions or within 21 days of discontinuing vorioxetine is contraindicated; do not use vorioxetine within 14 days of discontinuing MAOIs used for psychiatric conditions, nor should vorioxetine be started in patients receiving linezolid or intravenous methylene blue due to risk of serious adverse reactions including serotonin syndrome.
- ↑ risk of serotonin syndrome with other SSRIs, SNRIs, buspirone, fentanyl, lithium, tramadol, tricyclic antidepressants, triptans and tryptophan.
- Strong inhibitors of CYP2D6 bupropion, fluoxetine, paroxetine, or quinidine ↑ blood levels and effects (decrease dose by 50%).
- Strong inducers of CYP2D6 carbamazepine, phenytoin, rifampin ↓ blood levels and effectiveness, consider larger doses of vorioxetine if used for longer than 14 days (not to exceed three times original dose).
- ↑ risk of bleeding with aspirin, NSAIDs, anticoagulants, thrombolytics, antiplatelet agents and other drugs affecting coagulation.
↑ risk of serotonin syndrome with St. John's wort.
PO: (Adults) 10 mg once daily initially, may be ↑ to 20 mg once daily; some patients may only tolerate daily doses of 5 mg; CYP2D6 poor metabolizers–daily dose should not exceed 10 mg; Concurrent use of inhibitors of CYP2D6–↓ dose by 50%; Concurrent use of strong inducers of CYP2D6 for more than 14 days–consider ↑ dose (not to exceed three times original dose). If daily dose 15–20 mg/day, do not discontinue abruptly; taper to 10 mg/day for one wk before discontinuing.
Tablets: 5 mg, 10 mg, 20 mg
- Monitor mood changes. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
- Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care professional thereafter.
- Monitor for signs and symptoms of hypersensitivity reactions (rash, hives, swelling, difficulty breathing). Stop vortioxetine and treat symptomatically.
- Assess for sexual side effects (erectile dysfunction; decreased libido).
- Monitor for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Lab Test Considerations:
May cause hyponatremia.
- To avoid serotonin syndrome, allow at least 14 days between discontinuation of an MAO inhibitor and starting vortioxetine. Allow at least 21 days after stopping vortioxetine before starting an MAO inhibitor.
- PO: Administer once daily at the same time each day without regard to meals.
- Instruct patient to take vortioxetine at the same time each day as directed. Advise patient taking 15 mg/day or 20 mg/day of vortioxetine not to stop abruptly; may cause headache, muscle tension, mood swings, sudden outburst of anger, dizziness, and runny nose. Instruct patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Inform patient that nausea is common in first wk of therapy and is dose related. Usually decreases in frequency after first wk, but may persist.
- Caution patient to report signs and symptoms of hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness, and may worsen to hallucinations, syncope, seizures, coma, respiratory arrest, death) to health care professional promptly.
- Advise patient, family and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
- Caution patient and caregiver to look for signs of activation of mania/hypomania (greatly increased energy, severe sleeping problems, racing thoughts, reckless behavior, unusually grand ideas, excessive happiness or irritability, talking more or faster than usual), especially in patients with a history or family history of bipolar disorder, mania, or hypomania.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort. Advise patient to avoid taking other CNS depressants or alcohol. Also taking aspirin, NSAIDs, warfarin, or other anticoagulants may increase risk of bleeding.
- Inform patient that medication may cause decreased libido.
- Advise patient to notify health care professional if symptoms of hypersensitivity reaction or serotonin syndrome occur or if nausea persists.
- Instruct female patients to inform health care professional if pregnancy is planned or suspected, or if breastfeeding.
- Emphasize the importance of follow-up exams to monitor progress.
Evaluation/Desired OutcomesIncreased sense of well-being.
- Renewed interest in surroundings. May require 1–4 wk of therapy to obtain antidepressant effects.
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