If It Doesn’t Work

• Many patients have only 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

• 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.)

Best Augmenting Combos for Partial Response or Treatment Resistance

• Augmentation has not been systematically studied with tianeptine

Tests

• Baseline ECG is recommended for patients over age 50

TIANEPTINE: SIDE EFFECTS

How Drug Causes Side Effects

✽ Mild anticholinergic activity (less than some tricyclic antidepressants) could possibly lead to sedative effects, dry mouth, constipation, and blurred vision

• Most side effects are immediate but often go away with time

✽ Pharmacologic studies do not indicate tianeptine to be a potent alpha 1 antagonist or H1 antihistamine

Notable Side Effects

• Headache, dizziness, insomnia, sedation

• Nausea, constipation, abdominal pain, dry mouth

• Abnormal dreams

• Rare hepatotoxicity

• Tachycardia

Life-Threatening or Dangerous Side Effects

• Theoretically, lowered seizure threshold and rare seizures

• Theoretically, rare induction of mania and activation of suicidal ideation or behavior

• Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24

Weight Gain

• Not well studied

Sedation

• Occurs in significant minority

What to Do About Side Effects

• Wait

• Wait

• Wait

• Lower the dose

• In a few weeks, switch or add other drugs

Best Augmenting Agents for Side Effects

• Augmentation for side effects of tianeptine has not been systematically studied

TIANEPTINE: DOSING AND USE

Usual Dosage Range

• 37.5 mg/day

Dosage Forms

• Tablet 12.5 mg

How to Dose

• 12.5 mg 3 times/day

Dosing Tips

• Tianeptine’s rapid elimination necessitates strict adherence to the dosing schedule

✽ Short half-life means multiple daily doses

Overdose

• Effects are generally mild and nonfatal; unlikely to cause cardiovascular effects

Long-Term Use

• Safe

Habit Forming

• Abuse and dependence may occur, in particular in patients under 50 years of age with a history of drug or alcohol dependence

How to Stop

• Many patients tolerate 50% dose reduction for 3 days, then another 50% reduction for 3 days, then discontinuation

• If withdrawal symptoms emerge during discontinuation, raise dose to stop symptoms and then restart withdrawal much more slowly

Pharmacokinetics

• Not primarily metabolized by CYP 450 enzyme system

• Tianeptine is rapidly eliminated

• Half-life approximately 2.5 hours

Drug Interactions

• Activation and agitation, especially following switching or adding antidepressants, may represent the induction of a bipolar state, especially a mixed dysphoric bipolar II condition sometimes associated with suicidal ideation, and require the addition of lithium, a mood stabilizer or an atypical antipsychotic, and/or discontinuation of tianeptine

• Other drug interactions not well studied

Other Warnings/Precautions

• For elective surgery, tianeptine should be stopped 24–48 hours before general anesthesia is administered

• Generally, use only with extreme caution with MAO inhibitors; do not use until 14 days after MAOIs are stopped; do not start an MAOI for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing tianeptine

• When treating children, 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

• Warn patients and their caregivers about the possibility of activating side effects and advise them to report such symptoms immediately

• Monitor patients for activation of suicidal ideation, especially children and adolescents

Do Not Use

• If patient is taking an MAO inhibitor

• If patient is pregnant or nursing

• If there is a proven allergy to tianeptine

TIANEPTINE: SPECIAL POPULATIONS

Renal Impairment

• Dose should be reduced for severe impairment to 25 mg/day

Hepatic Impairment

• No dose adjustment necessary

Cardiac Impairment

• Baseline ECG is recommended

Elderly

• Baseline ECG is recommended for patients over age 50

• Dose should be reduced to 25 mg/day

• 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

• Not recommended for use in children under age 15