Restarting Medications After a One-Month Interruption
Restart asenapine (Saphris) 5 mg and bupropion XL 300 mg at their previous full doses immediately, but titrate lorazepam (Ativan) gradually from a lower starting dose to minimize rebound anxiety and withdrawal risk.
Asenapine (Saphris) 5 mg – Restart Protocol
Resume asenapine 5 mg sublingually twice daily immediately without titration. 1, 2
Rationale
- Asenapine has a short half-life and no significant withdrawal syndrome after one month of discontinuation 2, 3
- The 5 mg twice-daily dose is within the standard therapeutic range for both schizophrenia and bipolar disorder 1, 4
- No dose adjustment is required after a one-month gap because asenapine does not require gradual titration for safety 2, 5
Critical Administration Requirements
- Administer sublingually twice daily; do not swallow the tablet (bioavailability drops to <2% if swallowed) 1, 5
- Avoid all food and liquids for 10 minutes after each dose to ensure adequate absorption 1, 5
- Place the tablet under the tongue and allow complete dissolution without chewing or swallowing 5
Monitoring in the First Week
- Assess for somnolence, akathisia, and oral hypoesthesia (numbness), which are the most common adverse effects 4, 5
- Monitor for extrapyramidal symptoms, though asenapine has relatively low rates compared to typical antipsychotics 4
- Check for dysgeusia (altered taste), which may affect adherence 5
Bupropion XL 300 mg – Restart Protocol
Restart bupropion XL 300 mg once daily in the morning immediately without titration. 6, 7
Rationale
- After a one-month discontinuation, bupropion has been fully eliminated (half-life ≈21 hours for the parent compound) 6
- The FDA-approved dosing for bupropion XL allows direct initiation at 150 mg with escalation to 300 mg after only 4 days, so restarting at 300 mg after a brief interruption is safe 7
- Gradual titration is primarily recommended to minimize seizure risk during initial exposure, not after prior tolerance has been established 6, 7
Alternative Conservative Approach (If Seizure History or High Risk)
- If the patient has new seizure risk factors (e.g., head trauma, alcohol withdrawal, concurrent medications that lower seizure threshold), restart at 150 mg once daily for 4 days, then increase to 300 mg 6, 7
- Maximum dose must not exceed 450 mg/day to maintain seizure risk at 0.1% 6
Administration Instructions
- Take once daily in the morning to minimize insomnia risk 6
- Swallow the tablet whole; do not crush, divide, or chew (this would destroy the extended-release mechanism) 7
- May be taken with or without food 7
Monitoring in the First Two Weeks
- Assess for neuropsychiatric adverse effects, including agitation, restlessness, and behavioral changes 6
- Monitor blood pressure and heart rate, especially in the first 12 weeks, as bupropion can cause elevations 6
- Screen for suicidal ideation, particularly if the patient is under 24 years old (FDA black-box warning) 6
Lorazepam (Ativan) 1 mg – Restart Protocol
Do NOT restart lorazepam at the full 1 mg dose immediately; instead, begin with 0.25–0.5 mg and titrate gradually over 1–2 weeks to minimize rebound anxiety and dependence risk.
Rationale
- After one month without benzodiazepines, the patient's GABA-A receptor sensitivity has partially normalized 8
- Abrupt reinitiation at the full dose can cause excessive sedation, cognitive impairment, and rapid re-development of tolerance 8
- Benzodiazepines should be used at the lowest effective dose and for the shortest duration to avoid dependence 8
Recommended Titration Schedule
- Week 1: Start lorazepam 0.25–0.5 mg once or twice daily as needed for anxiety 8
- Week 2: If tolerated and clinically necessary, increase to 0.5–1 mg once or twice daily 8
- Maximum daily dose: Do not exceed 2 mg total per day without clear clinical justification 8
Critical Safety Considerations
- Avoid concurrent use with opioids (increases overdose death risk nearly four-fold) 8
- Limit duration to days-to-weeks, not months, to prevent tolerance and dependence 8
- Never discontinue abruptly if used for more than 2–4 weeks (risk of rebound anxiety, seizures, delirium tremens) 8
Alternative Non-Benzodiazepine Options
- Consider buspirone 5 mg twice daily (maximum 20 mg three times daily) for chronic anxiety management, though it takes 2–4 weeks to become effective 6
- Cognitive-behavioral therapy (CBT) should be offered alongside pharmacotherapy to reduce long-term benzodiazepine dependence 8
Common Pitfalls to Avoid
Asenapine-Specific Errors
- Swallowing the tablet instead of sublingual administration (reduces bioavailability to <2%) 1, 5
- Eating or drinking within 10 minutes of dosing (impairs absorption) 1, 5
- Underdosing due to fear of adverse effects (5 mg twice daily is the standard therapeutic dose) 2, 4
Bupropion-Specific Errors
- Exceeding 450 mg/day (dramatically increases seizure risk above 0.1%) 6
- Combining with MAOIs or starting within 14 days of MAOI discontinuation (risk of hypertensive crisis) 7
- Crushing or splitting the XL tablet (destroys extended-release properties and increases seizure risk) 7
Lorazepam-Specific Errors
- Restarting at the full 1 mg dose immediately (increases sedation and re-establishes tolerance rapidly) 8
- Using benzodiazepines as chronic standing medication (leads to dependence and withdrawal complications) 8
- Abrupt discontinuation after prolonged use (can precipitate seizures and delirium) 8
Expected Timeline for Therapeutic Effect
Asenapine
- Acute symptom control: 1–2 weeks for reduction in agitation or psychotic symptoms 2, 4
- Full therapeutic response: 4–6 weeks at therapeutic doses 4
Bupropion
- Initial energy improvement: 1–2 weeks (faster than most antidepressants) 6
- Full antidepressant response: 6–8 weeks at therapeutic doses 6, 7
Lorazepam
- Immediate anxiolytic effect: 30–60 minutes after sublingual or oral administration 8
- Peak plasma concentration: 2 hours after oral dosing 8
When to Seek Urgent Medical Attention
Asenapine
- Severe extrapyramidal symptoms (muscle rigidity, tremor, dystonia) 4
- Signs of neuroleptic malignant syndrome (fever, confusion, muscle rigidity, autonomic instability) 4
Bupropion
- Seizure activity (even a single seizure warrants immediate discontinuation) 6, 7
- Severe hypertension (systolic >180 mm Hg or diastolic >120 mm Hg) 6
- Acute suicidal ideation or behavioral changes 6