Medication Regimen Optimization for MDD, GAD, and Alcohol Use Disorder
Primary Recommendation
Continue Wellbutrin XL 300 mg daily and Acamprosate 333 mg (2 tablets TID) as the foundation of treatment, convert Hydroxyzine to scheduled dosing at 75 mg TID, increase Clonidine to 0.2 mg BID PRN as requested, maintain Gabapentin 800 mg TID, and discontinue Seroquel 50 mg TID PRN and nicotine gum. 1, 2
Rationale for Current Medications
Alcohol Use Disorder Management
Acamprosate is the only intervention with sufficient evidence demonstrating superiority over placebo for maintaining abstinence in detoxified alcohol-dependent patients in primary care settings for up to 12 months (odds ratio 1.86,95% CI 1.49 to 2.33). 2
The patient correctly declined adding naltrexone at this visit, as combination therapy (acamprosate + naltrexone) showed an odds ratio of 3.68 (95% CI 1.50 to 9.02) for abstinence, but this comes with increased risk of side effects and dropout rates. 2
Continue Acamprosate 333 mg (2 tablets TID) as monotherapy given his current stability and effectiveness. Reassess combination therapy only if relapse occurs or cravings intensify. 2
Depression Management
Wellbutrin XL 300 mg daily is appropriately dosed and well-tolerated. The FDA-approved dosing for MDD is 150 mg daily initially, increased to 300 mg after 4 days, which matches his current regimen. 1
Bupropion is particularly advantageous in this patient because it avoids sexual side effects that led to discontinuation of prior SSRIs/SNRIs, and it has demonstrated equivalent efficacy to SSRIs in treating MDD. 3, 2
His PHQ-9 score of 6 (mild depression) with functional impairment justifies continuing antidepressant therapy. Treatment should continue for at least 16-24 weeks after achieving response to prevent recurrence, and given his history of multiple episodes, even longer duration is beneficial. 2, 4
Anxiety Management
Gabapentin 800 mg TID should be continued as the patient reports benefit for both anxiety and mood. While gabapentin is not FDA-approved for GAD, it has been studied in anxiety disorders and requires careful titration with dosage reduction in renal insufficiency. 2
Converting Hydroxyzine 75 mg TID from PRN to scheduled dosing is appropriate given consistent use. Hydroxyzine demonstrated superiority over placebo for GAD (OR 0.30,95% CI 0.15 to 0.58) with acceptable tolerability (OR 1.00,95% CI 0.63 to 1.58). 5
Increasing Clonidine from 0.1 mg to 0.2 mg BID PRN is reasonable per patient request, with monitoring for sedation and hypotension. Clonidine can be effective for anxiety symptoms, particularly in patients with substance use history. 2
His GAD-7 score of 9 (moderate anxiety) indicates ongoing need for anxiolytic treatment. Second-generation antidepressants show no significant differences in treating anxiety symptoms in MDD patients, but venlafaxine showed some superiority over fluoxetine in one trial. 2
Medications to Discontinue
Discontinue Seroquel 50 mg TID PRN as the patient uses it infrequently with minimal benefit. Quetiapine showed an odds ratio of 6.75 (95% CI 1.20 to 38.05) for abstinence in one small study, but this evidence is low quality and does not justify continuation given lack of perceived benefit. 2
Discontinue nicotine gum as requested by the patient who does not use it and has no intention to use it.
Monitoring and Follow-up Strategy
Immediate Monitoring (First 1-2 Weeks)
Assess for suicidal ideation weekly given his history of suicide attempt and recent hospitalization. All patients on antidepressants require close monitoring for emergence of suicidal thoughts, particularly in the first 1-2 months of treatment. 2
Monitor for sedation with increased Clonidine dosing and scheduled Hydroxyzine. 5
Check blood pressure with Clonidine dose increase to detect hypotension. 2
Four-Week Follow-up
Reassess depression with PHQ-9 and anxiety with GAD-7 to determine if modifications are needed. If no adequate response within 6-8 weeks of any medication change, consider treatment modification. 2
Evaluate alcohol abstinence and cravings. If cravings persist or relapse occurs, reconsider adding naltrexone to acamprosate. 2
Monitor for adverse effects including: drowsiness/sedation (hydroxyzine, clonidine, gabapentin), dizziness (gabapentin, clonidine), and any emergence of agitation or behavioral changes. 5, 2
Long-term Considerations
Continue antidepressant therapy for 4-9 months minimum after satisfactory response, and given his multiple depressive episodes, consider indefinite maintenance therapy. 2
Acamprosate should continue as long as abstinence is maintained and the medication is well-tolerated, with evidence supporting up to 12 months of treatment. 2
Periodically reassess need for anxiolytic medications, particularly benzodiazepine alternatives like hydroxyzine and clonidine, as GAD is a chronic condition requiring long-term management. 6
Critical Pitfalls to Avoid
Do not abruptly discontinue Wellbutrin XL 300 mg—taper to 150 mg daily for at least one week before complete discontinuation if ever needed. 1
Do not add SSRIs or SNRIs given his history of sexual side effects leading to discontinuation, unless bupropion fails completely. 2, 3
Avoid combining bupropion with MAOIs—allow at least 14 days between discontinuation of an MAOI and initiation of bupropion, and vice versa. 1
Monitor for seizure risk with bupropion, particularly if doses exceed 300 mg daily or if other seizure risk factors emerge. 1
Adjust gabapentin dosing if renal function declines, as it requires dose reduction in renal insufficiency. 2
Do not prescribe opioids given his alcohol use disorder history and current recovery status, as this would significantly increase relapse risk. 2