NEFAZODONE

Class

• Neuroscience-based Nomenclature: serotonin receptor antagonist
• SARI (serotonin 2 antagonist/reuptake inhibitor); antidepressant

NEFAZODONE commonly prescribed for

(Bold for FDA approved)

How NEFAZODONE works

• Blocks serotonin 2A receptors potently

• Blocks serotonin reuptake pump (serotonin transporter) and norepinephrine reuptake pump (norepinephrine transporter) less potently

How long until NEFAZODONE works

• Can improve insomnia and anxiety early after initiating dosing

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

• If it is not working within 6–8 weeks for depression, 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, dry mouth, constipation, dyspepsia, increased appetite

• Headache, dizziness, vision changes, sedation, insomnia, agitation, confusion, memory impairment

• Ataxia, paresthesia, asthenia

• Cough increased

• Rare postural hypotension

Life Threatening Side Effects

• Rare seizures

• Rare induction of mania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

• Rare priapism (no causal relationship established)

• Hepatic failure requiring liver transplant and/or fatal

weight gain

unusual

sedation

common

What to do about NEFAZODONE side effects

• Wait

• Wait

• Wait

• Take once daily at night to reduce daytime sedation

• Lower the dose and try titrating again more slowly as tolerated

• Switch to another agent

usual dosage range

• 300–600 mg/day

Dosage Forms

• Tablet 50 mg, 100 mg scored, 150 mg scored, 200 mg, 250 mg

long term use

• Safe

habit forming

• No

Renal Impairment

• No dose adjustment necessary

Hepatic Impairment

• Contraindicated in patients with known hepatic impairment

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension

Elderly

• Recommended to initiate treatment at half the usual adult dose, but to follow the same titration schedule as with younger patients, including same ultimate dose

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

Children and Adolescents

• 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 inform parents or guardians of this risk so they can help observe child or adolescent patients

• Safety and efficacy have not been established

• Preliminary research indicates efficacy and tolerability of nefazodone in children and adolescents with depression

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

• 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

Breast Feeding

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

• Trace amounts may be present in nursing children whose mothers are on nefazodone

• 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