nefazodone (Serzone, Nefazodone 5HT2, Serzone 5HT2)
Classes: Antidepressants, Other; Antidepressants, SSRI/Antagonist
Dosing and uses of Serzone, Nefazodone 5HT2 (nefazodone)
Adult dosage forms and strengths
tablet
- 50mg
- 100mg
- 150mg
- 200mg
- 250mg
Depression
Initial: 100 mg PO q12hr
Increase by 50-100 mg/dose at 1 week intervals
Geriatric
Initial: 50 mg PO q12hr (reduced clearance, increased side effects)
Increase by 50-100 mg/dose at 1 week intervals
Maintenance: 200-400 mg/day divided q12hr
Pediatric dosage forms and strengths
Safety & efficacy not established
Serzone, Nefazodone 5HT2 (nefazodone) adverse (side) effects
>10%
Headache (31-35%)
Somnolence (21-25%)
Nausea (21-25%)
Xerostomia (21-25%)
Dizziness (15-20%)
Asthenia (11-15%)
Constipation (11-15%)
Insomnia (11-15%)
1-10%
Infection (6-10%)
Dyspepsia (6-10%)
Lightheadedness (6-10%)
Confusion (6-10%)
Blurred vision (6-10%)
Abnormal vision (6-10%)
Increased appetite (1-5%)
Memory loss (1-5%)
Paresthesia (1-5%)
Vasodilation (1-5%)
Decreased concentration (1-5%)
Ataxia (1-5%)
Decreased libido (1-5%)
Breast pain (1-5%)
Decreased hematocrit (1-5%)
Agitation with discontinuation (1-5%)
Orthostatic hypotension (2.6%)
Bradycardia (1.5%)
Frequency not defined
Hypomania
Mania
Seizure
Suicidal thoughts
Suicide
Worsening depression
Liver failure (rare, 1 in 250,000-300,000)
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years
In children and young adults, 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 initial 1-2 months of therapy and 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
This drug is not approved for use in pediatric patients
Contraindications
Co-administration with terfenadine (discontinued), astemizole (discontinued), cisapride, pimozide, carbamazepine
Concurrent administration with alprazolam or triazolam (reduce dose by 50% and 75%, respectively)
Hypersensitivity to nefazadone or other phenylpiperazine antidepressants
Co-administration with MAO inhibitors or within 14 days of administration
Avoid during breast-feeding
Cautions
Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 yo)
May take several weeks to achieve full response
May cause anticholinergic effects
Use caution in patients experiencing xerostomia, visual problems, paralytic ileus, BPH, urinary retention, or decreased motility
Hepatic failure associated with nefazodone use
Sedation may occur; may impair physical or mental abilities
Orthostatic hypotension may occur
Discontinue MAOI 14 d before nefazodone
Discontinue nefazodone 7 d before starting an MAOI
Discontinued in Canada following severe adverse hepatic events
Pregnancy and lactation
Pregnancy category: C
Lactation: unknown; use with caution
Pregnancy 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.
Pharmacology of Serzone, Nefazodone 5HT2 (nefazodone)
Mechanism of action
Antidepressant structurally unrelated to SSRI, tricyclics, tetracyclics, or MAO inhibitors but inhibits neuronal reuptake of serotonin & norepinephrine; it is also a 5-HT2 and alpha1 receptor antagonist
Pharmacokinetics
Half-life elimination: 2-4 hrs
Peak Plasma Time: 1 hr
Bioavailability: 20% (decreased by food)
Protein Bound: >99%
Vd: 0.22-0.87 L/kg
Metabolism: hepatic P450 enzyme CYP3A4
Metabolites: hydroxynefazodone (HO-NEF), metachlorphenylpiperazine (mCPP)
Excretion: Urine (55%); feces (20-30%)
Dialyzable: No
Enzymes inhibited: CYP3A4