Usual Adult Dose for Depression

Initial dose: 200 mg orally per day in two divided doses
Maintenance dose: 300 to 600 mg orally per day

Comments:

• Dose increases should occur in increments of 100 mg per day to 200 mg per day, on a 2 times a day schedule, and at intervals of no less than 1 week.
• Several weeks may be required for full effect.
• Patients in long-term studies were followed for up to 52 weeks; patients receiving prolonged treatment should be periodically assessed for usefulness.

Use: Treatment of depression, including major depressive disorder

Usual Geriatric Dose for Depression

Elderly or debilitated patients:

• Initial dose: 100 mg orally per day administered in two divided doses
• Maintenance dose: Up to 300 to 600 mg orally per day

Comments:

• Since these patients often have reduced drug clearance and/or increased sensitivity to the side effects, it may be appropriate to modify the rate of subsequent dose titration.
• Several weeks may be required for full effect.
• Patients in long-term studies were followed for up to 52 weeks; patients receiving prolonged treatment should be periodically assessed for usefulness.

Use: Treatment of depression, including major depressive disorder

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Patients with evidence of liver injury: Contraindicated

This drug should be discontinued and not restarted if patients develop signs of liver dysfunction (AST or ALT greater than or equal to 3 times the upper limit of normal [3x ULN]).

Dose Adjustments

Use with an MAOI:

• Starting this drug: Allow at least 14 days after stopping an MAOI to start this drug.
• Stopping this drug: Allow at least 7 days after stopping this drug to start an MAOI.

Dose adjustments may be required on the basis of clinical response when this drug is coadministered with buspirone, propanolol, and desipramine.

Use with Triazolam:

• Coadministration should be avoided for most patients.
• If use is deemed necessary AND if the dosage form of triazolam permits sufficient dosage reduction, providers should consider reducing the initial triazolam dose by 75%.

Precautions

US BOXED WARNINGS:
Hepatotoxicity:

• Cases of life-threatening hepatic failure have been reported in patients treated with this drug. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,00 patient-years of treatment. The total patient-years is a summation of each patient's duration of exposure expressed in years. For example, 1 patient-year is equal to 2 patients each treated for 6 months, 3 patients each treated for 4 months, etc.
• Ordinarily, treatment with this drug should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. There is no evidence that pre-existing liver disease increases the likelihood of developing liver failure; however, baseline abnormalities can complicate patient monitoring.
• Patients should be advised to be alert for signs/symptoms of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they occur.
• This drug should be discontinued if clinical signs/symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels at least 3 times the upper limit of normal, while on this drug should be withdrawn from treatment. These patients should be presumed to be at increased risk for liver injury if this drug is reintroduced. Accordingly, such patients should not be considered for re-treatment.

Suicidality and Antidepressant Drugs:

• Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of this drug or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
• Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.
• Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide.
• Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changed in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Families and caregivers should be advised of the need for close observation and communication with the prescriber.
• This drug is not approved for use in pediatric patients.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Dialysis is not expected to remove this drug.

Other Comments

Storage requirements:

• Protect from light.

General:

• Prescribers should consider the risk of hepatic failure associated with this drug prior to starting treatment.
• Major depressive disorder includes a prominent and relatively persistent depressed/dysphoric mood that typically interferes with daily functioning nearly every day for at least 2 weeks AND at least 5 of the following: depressed mood, loss of interest in usual activities, significant weight/appetite changes, insomnia/hypersomnia, psychomotor agitation/retardation, increased fatigue, feelings of guilt/worthlessness, slowed thinking/impaired concentration, a suicide attempt, or suicidal ideation.

Monitoring:

• Hepatic: Serum transaminases, signs/symptoms of liver dysfunction
• Psychiatric: Suicidal thoughts and behaviors

Patient advice:

• Patients should be cautioned accordingly since this drug may impair the mental and/or physical abilities required for the performance of operating an automobile or machinery.
• Patients should be instructed to avoid abrupt discontinuation of treatment.
• Patients should be advised to immediately report any signs/symptoms of liver dysfunction, allergic reactions, visual disturbances, or new/worsening depression or suicidality.
• Patients and caregivers should be told to avoid alcohol during treatment. A healthcare provider should be consulted prior to talking or planning on taking additional medications concomitantly.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.