THERAPEUTICS

Brands

• Marplan
• see index for additional brand names

Generic?

• Not in U.S.

Class

• Monoamine oxidase inhibitor (MAOI)

Commonly Prescribed For

• (bold for FDA approved)
• Depression
• Treatment-resistant depression
• Treatment-resistant panic disorder
• Treatment-resistant social anxiety disorder

How The Drug Works

• Irreversibly blocks monoamine oxidase (MAO) from breaking down norepinephrine, serotonin, and dopamine
• This presumably boosts noradrenergic, serotonergic, and dopaminergic neurotransmission

How Long Until It Works

• Onset of therapeutic actions usually not immediate, but often delayed 2-4 weeks
• If it is not working within 6-8 weeks, 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
• 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

• Augmentation of MAOIs has not been systematically studied, and this is something for the expert, to be done with caution and with careful monitoring
• A stimulant such as d-amphetamine or methylphenidate (with caution; may activate bipolar disorder and suicidal ideation; may elevate blood pressure)
• Lithium
• Mood stabilizing anticonvulsants
• Atypical antipsychotics (with special caution for those agents with monoamine reuptake blocking properties, such as ziprasidone and zotepine)

Tests

• Patients should be monitored for changes in blood pressure
• Patients receiving high doses or long-term treatment should have hepatic function evaluated periodically
• Since MAO inhibitors are frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0–29.9) or obese (BMI ≥30)
• Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100–125 mg/dL), diabetes (fasting plasma glucose >126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management
• Monitor weight and BMI during treatment
• While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different antidepressant