How to manage tianeptine withdrawal in a patient with adrenal insufficiency on high-dose steroids (hydrocortisone 100 mg twice daily) and midodrine (5 mg three times daily)?

Managing Tianeptine Withdrawal in a Patient with Adrenal Insufficiency

Continue the current high-dose hydrocortisone 100 mg twice daily without tapering during tianeptine withdrawal, as this represents appropriate stress-dose coverage for a major physiological stressor, and maintain midodrine for blood pressure support while managing withdrawal symptoms with buprenorphine/naloxone or supportive care. 1, 2

Maintain Stress-Dose Glucocorticoid Coverage

The current hydrocortisone regimen of 100 mg twice daily (200 mg total daily) is appropriate and should be continued throughout the withdrawal period without reduction. 1

• Tianeptine withdrawal constitutes a major physiological stress comparable to severe illness or surgery, which requires stress-dose glucocorticoid coverage in patients with adrenal insufficiency 1, 2, 3
• The consensus guidelines for primary adrenal insufficiency recommend 100 mg hydrocortisone every 6 hours (400 mg daily) for major surgery or severe stress, continuing until the patient is stable 1
• Your patient's current dose of 200 mg daily represents an intermediate stress dose that is reasonable for managing withdrawal 1, 4
• Do not taper the hydrocortisone until withdrawal symptoms have completely resolved and the patient is clinically stable for at least 24-48 hours 1, 4

Critical Monitoring for Adrenal Crisis

Remain vigilant for signs of adrenal crisis, as withdrawal symptoms can mask or mimic crisis symptoms, and nausea/vomiting during withdrawal poses particular risk. 1

• Nausea and vomiting occur in tianeptine withdrawal and are also precipitating events for adrenal crisis in 6-8 per 100 patient-years 1, 5, 3
• If the patient develops persistent vomiting and cannot absorb oral hydrocortisone, immediately switch to IV hydrocortisone 100 mg bolus followed by 100 mg every 6 hours 1
• Monitor for confusion, severe weakness, hypotension, or altered mental status—these require immediate IV hydrocortisone and aggressive fluid resuscitation with 0.9% saline at 1 L/hour 1
• Never delay treatment of suspected adrenal crisis for diagnostic procedures—the mortality is high if untreated 1

Tianeptine Withdrawal Management Protocol

Treat tianeptine withdrawal with buprenorphine/naloxone as first-line therapy, as tianeptine has opioid agonist activity and withdrawal resembles opioid withdrawal. 2, 3

• The most recent case report (2025) successfully managed severe tianeptine withdrawal (8-20 g daily use) with buprenorphine/naloxone, with symptom improvement within 3 days 2
• Start buprenorphine/naloxone once the patient is in moderate withdrawal (typically 12-24 hours after last tianeptine dose) to avoid precipitated withdrawal 2
• Alternative supportive management includes phenothiazines (cyamemazine) for sedation and benzodiazepines (tetrazepam) for myalgia and muscle relaxation if buprenorphine is contraindicated 5
• Withdrawal symptoms include myalgia, cold feeling, nausea, vomiting, abdominal pain, and anxiety—these typically resolve over 4-7 days with appropriate treatment 5, 3

Midodrine Management During Withdrawal

Continue midodrine 5 mg three times daily for blood pressure support, as both adrenal insufficiency and tianeptine withdrawal can cause hypotension. 1

• Midodrine provides alpha-agonist support for orthostatic hypotension, which is common in adrenal insufficiency even with adequate glucocorticoid replacement 1
• Monitor blood pressure in supine and standing positions to assess for orthostatic changes 4
• Once withdrawal is complete and the patient is stable on maintenance hydrocortisone, reassess the need for midodrine by checking for orthostatic hypotension and considering fludrocortisone optimization 4

Tapering Strategy After Withdrawal Resolution

Once tianeptine withdrawal symptoms have completely resolved and the patient is clinically stable for 48 hours, begin tapering hydrocortisone to maintenance dosing over 3-5 days. 1, 4

• Taper from 100 mg twice daily to double the maintenance dose (40-50 mg daily in divided doses) for 24-48 hours 1
• Then reduce to standard maintenance dosing of 15-25 mg daily, typically given as 10 mg upon awakening and 5 mg in early afternoon 4, 6
• If the patient has primary adrenal insufficiency, ensure fludrocortisone 0.05-0.1 mg daily is prescribed for mineralocorticoid replacement 4, 6
• Monitor for signs of under-replacement (fatigue, nausea, orthostatic hypotension) or over-replacement (weight gain, hypertension, hyperglycemia) during the taper 4, 6

Critical Pitfalls to Avoid

• Do not prematurely taper steroids while withdrawal symptoms are active—this risks precipitating adrenal crisis during a period of high physiological stress 1
• Do not assume the patient can absorb oral medications if vomiting occurs—switch to parenteral hydrocortisone immediately 1
• Do not rely on electrolyte abnormalities to diagnose adrenal crisis—hyperkalemia is present in only 50% of cases and hyponatremia may be mild 1, 7
• Do not discharge the patient without ensuring they have emergency injectable hydrocortisone, medical alert identification, and education on stress dosing 1, 4, 6