In Collaboration With

THERAPEUTICS

Brands

• Dutonin
• see index for additional brand names

Generic?

• Yes

Class

• SARI (serotonin 2 antagonist/reuptake inhibitor); antidepressant

Commonly Prescribed For

• (bold for FDA approved)
• Depression
• Relapse prevention in MDD
• Panic disorder
• Posttraumatic stress disorder

How The Drug Works

• Blocks serotonin 2A receptors potently
• Blocks serotonin reuptake pump (serotonin transporter) and norepinephrine reuptake pump (norepinephrine transporter) less potently

How Long Until It Works

• Can improve insomnia and anxiety early after initiating dosing
• Onset of therapeutic actions usually not immediate, but often delayed 2 to 4 weeks
• If it is not working within 6 to 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

If It Works

• The goal of treatment is complete remission of current symptoms as well as prevention of future relapses
• Treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped
• Continue treatment until all symptoms are gone (remission)
• Once symptoms gone, continue treating for 1 year for the first episode of depression
• For second and subsequent episodes of depression, treatment may need to be indefinite
• Use in anxiety disorders may also need to be indefinite

If It Doesn’t Work

• Many patients only have a partial response where some symptoms are improved but others persist (especially insomnia, fatigue, and problems concentrating)
• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
• Some patients who have an initial response may relapse even though they continue treatment, sometimes called “poop-out”
• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent
• Consider psychotherapy, especially cognitive-behavioral psychotherapies, which have been specifically shown to enhance nefazodone’s antidepressant actions
• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)
• Some patients may experience apparent lack of consistent efficacy due to activation of latent or underlying bipolar disorder, and require antidepressant discontinuation and a switch to a mood stabilizer

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Venlafaxine and escitalopram may be the best tolerated when switching or augmenting with a serotonin reuptake inhibitor, as neither is a potent CYP450 2D6 inhibitor (use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation)
• Modafinil, especially for fatigue, sleepiness, and lack of concentration
• Mood stabilizers or atypical antipsychotics for bipolar depression, psychotic depression or treatment-resistant depression
• Benzodiazepines for anxiety, but give alprazolam cautiously with nefazodone as alprazolam levels can be much higher in the presence of nefazodone
• Classically, lithium, buspirone, or thyroid hormone

Tests

• Liver function testing is not required but is often prudent given the small but finite risk of serious hepatoxicity
• However, to date no clinical strategy, including routine liver function tests, has been identified to reduce the risk of irreversible liver failure