What is the best approach to restart medications for a patient who stopped taking Wellbutrin (bupropion) XL, Lexapro (escitalopram) 25mg, clonidine 0.1mg, trazodone 50mg, and hydroxyzine tid over a year ago due to non-adherence?

Restarting Medications After Year-Long Non-Adherence in Inpatient Setting

Immediate Assessment and Prioritization

Begin by restarting the most critical medication for psychiatric stability—the antidepressant—while simultaneously addressing the polypharmacy that likely contributed to non-adherence. 1

Step 1: Restart Core Antidepressant Therapy

• Start with escitalopram (Lexapro) at 10mg daily, which is 50% of the previous dose, as this is the primary treatment for both depression and anxiety 1
• Alternatively, restart bupropion XL at 150mg daily (50% of typical maintenance dose), particularly if the patient has concerns about sexual side effects or weight gain 2, 3
• Do not restart both antidepressants simultaneously—choose one based on the patient's primary symptoms and previous response 3
• Monitor closely for the first 1-2 weeks for emergence of suicidal ideation, agitation, anxiety, panic attacks, insomnia, irritability, hostility, or unusual behavioral changes 4, 2

Step 2: Simplify Sleep Medication Regimen

The patient was on two sedating medications (clonidine and trazodone) for sleep, which represents unnecessary polypharmacy. 5

• Restart only trazodone 50mg at bedtime for sleep, as it provides both sleep improvement and additional antidepressant effects 3, 6, 7
• Do not restart clonidine unless there is documented hypertension requiring treatment, as abrupt discontinuation over a year ago means no rebound hypertension risk remains 1
• Trazodone is particularly appropriate if restarting bupropion, as bupropion may not improve sleep parameters as effectively as SSRIs 6, 7

Step 3: Address Anxiety Management

• Restart hydroxyzine 25-50mg three times daily as needed for acute anxiety symptoms, as this provides non-addictive anxiolytic effects 1
• Reassess need for scheduled dosing versus PRN use after 2-4 weeks once the SSRI reaches therapeutic effect 4

Titration Schedule and Monitoring

Week 1-2: Initial Restart Phase

• Schedule face-to-face or telephone contact within 1 week of medication initiation to assess for adverse effects, suicidal ideation, and adherence 4
• Monitor specifically for: ongoing depressive symptoms, suicide risk, medication side effects, adherence barriers, and environmental stressors 4
• If using bupropion, watch for seizure risk factors including alcohol use, benzodiazepine use, or metabolic disorders 2

Week 3-4: Dose Optimization

• If escitalopram was chosen and patient tolerates 10mg well, increase to 15mg daily, then to previous dose of 25mg if needed (note: maximum FDA-approved dose is 20mg; 25mg is off-label) 4
• If bupropion was chosen, increase from 150mg to 300mg XL daily after 3-4 weeks if tolerated 2, 3
• Allow 14-21 days at each dose level before determining inadequate response 8

Months 2-3: Response Assessment

• Expect onset of antidepressant action at 2 weeks with full efficacy at 4-6 weeks 3
• Continue monthly monitoring for 6-12 months after full symptom resolution 4
• If trazodone was used for sleep during initial treatment, discontinue after 6 weeks to determine if primary antidepressant has improved sleep 6

Critical Monitoring Parameters

Suicide Risk Assessment

• The greatest risk of relapse occurs in the first 8-12 weeks after restarting antidepressants 4
• Prescribe the smallest quantity of tablets consistent with good management to reduce overdose risk 2
• Instruct patient and family to report immediately: suicidal thoughts, worsening depression, severe agitation, panic attacks, or aggressive behavior 2

Drug Interaction Considerations

• Both bupropion and escitalopram can interact through CYP2D6 metabolism 9
• Bupropion inhibits CYP2D6, which can increase SSRI levels and potentially cause serotonin syndrome when combined 9
• If unusual side effects occur at low doses, consider pharmacogenetic testing for CYP2D6 status 8

Maintenance and Relapse Prevention

• Continue antidepressant therapy for 6-12 months after complete symptom resolution 4
• If this represents a recurrent depressive episode, consider maintenance treatment for up to 2 years 4
• Monthly monitoring should continue throughout the maintenance phase 4

Common Pitfalls to Avoid

Do Not:

• Restart all five medications simultaneously—this recreates the polypharmacy that contributed to non-adherence 1, 5
• Assume the patient needs the same doses as before—start at 50% of previous maintenance doses to minimize side effects 1
• Misinterpret early symptoms of serotonin syndrome or activation as worsening depression—this can lead to inappropriate dose increases 9
• Discontinue medications prematurely if symptoms improve—this significantly increases relapse risk 4, 2
• Ignore adherence barriers—address cost, complexity, side effects, and patient understanding before discharge 1, 5

Critical Safety Consideration:

If combining bupropion with trazodone or any SSRI, monitor closely for serotonin syndrome (myoclonus, confusion, agitation, dysautonomia, altered consciousness), as bupropion's CYP2D6 inhibition can increase serotonergic medication levels 9