What is the safest way to taper an adult woman who is taking low‑dose paroxetine 12.5 mg for hot flushes, chlordiazepoxide, and amitriptyline for depression and anxiety?

Tapering Strategy for Paroxetine, Chlordiazepoxide, and Amitriptyline in an Adult Woman

Direct Recommendation

Taper paroxetine first over 4–6 weeks, then taper chlordiazepoxide over 4–8 weeks, and finally taper amitriptyline over 2–4 weeks, using the smallest dose decrements possible at each step to minimize withdrawal symptoms. 1

---

Evidence-Based Tapering Sequence and Rationale

Step 1: Taper Paroxetine First (Weeks 1–6)

Paroxetine carries the highest risk of discontinuation syndrome among these three medications and must be tapered most gradually. 1, 2, 3

Paroxetine Tapering Protocol

• Week 1–2: Reduce from 12.5 mg to 10 mg daily 1
• Week 3–4: Reduce from 10 mg to 7.5 mg daily 1
• Week 5–6: Reduce from 7.5 mg to 5 mg daily 1
• Week 7–8: Reduce from 5 mg to 2.5 mg daily 1
• Week 9–10: Consider frequency reduction—take 2.5 mg every other day before complete cessation 1

Critical Paroxetine Discontinuation Considerations

• Paroxetine discontinuation syndrome includes dizziness, fatigue, myalgias, chills, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, paresthesias, anxiety, irritability, agitation, and abnormal dreams 1, 3
• Abrupt discontinuation dramatically increases withdrawal risk—patients who stopped paroxetine abruptly experienced significantly higher rates of discontinuation syndrome compared to those who tapered 2
• Patients who experienced adverse reactions during early paroxetine treatment are at significantly higher risk for discontinuation syndrome and require extra vigilance during tapering 2
• Withdrawal symptoms typically appear within 1–3 days of dose reduction 1
• If withdrawal symptoms emerge, immediately return to the previous dose and slow the taper rate, extending the interval between reductions to 2–3 weeks instead of 1–2 weeks 1, 3

---

Step 2: Taper Chlordiazepoxide Second (Weeks 7–14 or Weeks 7–22)

Begin tapering chlordiazepoxide only after paroxetine has been completely discontinued for at least 1–2 weeks to avoid compounding withdrawal syndromes. 4

Chlordiazepoxide Tapering Protocol

• Reduce the daily dose by 25% every 1–2 weeks 4
• For patients on long-term benzodiazepines or higher doses, extend the taper to 4–8 weeks or longer 4
• The EMPOWER trial demonstrated that gradual reduction over many weeks achieved 27% cessation rates versus 5% in controls 4

Critical Benzodiazepine Discontinuation Considerations

• Abrupt benzodiazepine withdrawal can cause rebound anxiety, hallucinations, seizures, delirium tremens, and rarely death 4
• Benzodiazepines are associated with cognitive impairment, reduced mobility, falls, fractures, and addiction, making discontinuation medically necessary 4
• Current consensus guidelines advise benzodiazepine use solely on a short-term basis 4
• Cognitive-behavioral therapy increases benzodiazepine tapering success rates and should be offered during the taper 4
• If withdrawal symptoms persist despite dose restoration, consider adjunctive pharmacological interventions such as carbamazepine, pregabalin, or paroxetine (though paroxetine has already been discontinued in this case), though evidence for these agents is limited 4

---

Step 3: Taper Amitriptyline Last (Weeks 15–18 or Weeks 23–26)

Begin tapering amitriptyline only after chlordiazepoxide has been completely discontinued for at least 1–2 weeks. 4

Amitriptyline Tapering Protocol

• Reduce the dose by 25% every 1–2 weeks 4
• For patients on low-dose amitriptyline (as in this case), a 2–4 week taper is typically sufficient 4
• Gradual withdrawal over more than 1 month is recommended for sedating antidepressants to prevent discontinuation syndromes 4

Critical Tricyclic Antidepressant Discontinuation Considerations

• Tricyclic antidepressants like amitriptyline require gradual tapering to minimize withdrawal effects 4
• Withdrawal symptoms can include rebound anxiety, insomnia, and autonomic instability 3
• If withdrawal symptoms emerge, return to the previous dose and extend the taper duration 1

---

Alternative Non-Pharmacological Interventions During Tapering

• Cognitive-behavioral therapy should be initiated during the benzodiazepine taper to increase success rates and address underlying anxiety and depression 4
• Psychological treatments including problem-solving, interpersonal therapy, and supportive psychotherapy should be pursued as alternatives to pharmacotherapy 4
• Integrative strategies including prayer, massage, aromatherapy, music therapy, and art therapy can support the tapering process 4

---

Monitoring and Management During Tapering

• Assess for withdrawal symptoms at each dose reduction step, including physical symptoms (dizziness, nausea, fatigue, myalgias, sensory disturbances) and psychological symptoms (anxiety, irritability, agitation, insomnia) 1, 3
• Schedule follow-up visits every 1–2 weeks during the paroxetine and chlordiazepoxide tapers to monitor for withdrawal symptoms and provide reassurance 1
• If mild withdrawal symptoms occur, reassure the patient that they are usually transient and self-limiting 3
• For more severe withdrawal symptoms, reinstitute the previous dose and slow the rate of taper 3
• Never mistake withdrawal symptoms for relapse of depression or anxiety—misdiagnosis may lead to unnecessary reinstitution of medications or costly medical workups 3

---

Common Pitfalls to Avoid

• Never taper multiple medications simultaneously—this compounds withdrawal syndromes and makes it impossible to identify which medication is causing symptoms 4, 1
• Never taper paroxetine faster than 2.5 mg every 1–2 weeks—rapid discontinuation dramatically increases withdrawal risk 1, 2
• Never abruptly discontinue chlordiazepoxide—this can precipitate life-threatening seizures and delirium 4
• Do not confuse withdrawal symptoms with relapse—withdrawal symptoms typically emerge within 1–3 days of dose reduction and resolve with dose restoration, whereas relapse develops more gradually over weeks 1, 3
• Avoid "cold referrals" to other clinicians—the prescribing clinician is obligated to either offer a comfortable tapering regimen or obtain agreement from another physician to provide care 1

---

Expected Timeline for Complete Discontinuation

• Total tapering duration: 13–26 weeks (approximately 3–6 months) depending on individual tolerance and withdrawal symptom severity 4, 1
• Paroxetine taper: 6–10 weeks 1
• Chlordiazepoxide taper: 4–8 weeks 4
• Amitriptyline taper: 2–4 weeks 4
• Allow 1–2 weeks between completing one medication taper and starting the next 4, 1