Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• 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 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

NEFAZODONE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Depressed patients with anxiety or insomnia who do not respond to other antidepressants

• Patients with SSRI-induced sexual dysfunction

Potential Disadvantages

• Patients who have difficulty with a long titration period or twice daily dosing

• Patients with hepatic impairment

Primary Target Symptoms

• Depressed mood

• Sleep disturbance

• Anxiety

Pearls

• Preliminary data for efficacy in panic disorder and PTSD

• Fluoxetine and paroxetine may not be tolerated when switching or augmenting

• For elderly patients with early dementia and agitated depression, consider nefazodone in the morning and additional trazodone at night

• Anecdotal reports suggest that nefazodone may be effective in treating PMDD

✽ Studies suggest that cognitive-behavioral psychotherapy enhances the efficacy of nefazodone in chronic depression

✽ Risk of hepatotoxicity makes this agent a second-line choice and has led to its withdrawal from some markets, including the withdrawal of Serzone from the U.S. market

• Rarely, patients may complain of visual “trails” or after-images on nefazodone

Suggested Reading

DeVane CL, Grothe DR, Smith SL. Pharmacology of antidepressants: focus on nefazodone. J Clin Psychiatry 2002;63(1):10–17.

Dunner DL, Laird LK, Zajecka J, Bailey L, Sussman N, Seabolt JL. Six-year perspectives on the safety and tolerability of nefazodone. J Clin Psychiatry 2002;63(1):32–41.

Khouzam HR. The antidepressant nefazodone. A review of its pharmacology, clinical efficacy, adverse effects, dosage, and administration. J Psychosocial Nursing Ment Health Serv 2000;38:20–25.

Masand PS, Gupta S. Long-term side effects of newer-generation antidepressants: SSRIs, venlafaxine, nefazodone, bupropion, and mirtazapine. Ann Clin Psychiatry 2002;14:175–82.

Schatzberg AF, Prather MR, Keller MB, Rush AJ, Laird LK, Wright CW. Clinical use of nefazodone in major depression: a 6-year perspective. J Clin Psychiatry 2002;63(1):18–31.

NORTRIPTYLINE

NORTRIPTYLINE: THERAPEUTICS

Brands

• Pamelor

see index for additional brand names

Generic?

Yes

Class

• Tricyclic antidepressant (TCA)

• Predominantly a norepinephrine/noradrenaline reuptake inhibitor

Commonly Prescribed for

(bold for FDA approved)

• Major depressive disorder

• Anxiety

• Insomnia

• Neuropathic pain/chronic pain

• Treatment-resistant depression

How the Drug Works

• Boosts neurotransmitter norepinephrine/noradrenaline

• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission

• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, nortriptyline can increase dopamine neurotransmission in this part of the brain

• A more potent inhibitor of norepinephrine reuptake pump than serotonin reuptake pump (serotonin transporter)

• At high doses may also boost neurotransmitter serotonin and presumably increase serotonergic neurotransmission