In a 40‑year‑old patient with 3 months of alcohol abstinence, alcoholic peripheral neuropathy, social anxiety disorder, generalized anxiety disorder, and depression who is taking buspirone 7.5 mg twice daily (ineffective and poorly tolerated) and gabapentin for neuropathy (causing forgetfulness), what work‑up should be performed and what medication adjustments are recommended?

Management of Ineffective Buspirone and Gabapentin-Related Cognitive Impairment in a Recovering Alcoholic

Discontinue buspirone immediately and switch to an SSRI (paroxetine 20 mg daily or sertraline 50–200 mg daily) for the anxiety disorders, while optimizing gabapentin dosing or switching to a tricyclic antidepressant (nortriptyline 25–150 mg daily) for neuropathic pain to address the cognitive complaints. 1

Immediate Medication Adjustments

Discontinue Buspirone

• Buspirone is ineffective in this patient and poorly tolerated, which is consistent with its known limitations: it requires 2–4 weeks for onset of action, produces only mild anxiolytic effects, and is not recommended as first-line therapy for social phobia or generalized anxiety disorder when SSRIs are available. 2, 3
• Although buspirone showed some benefit in anxious alcoholics in older trials (reduced anxiety, slower return to heavy drinking), these studies enrolled actively drinking patients during early abstinence—not patients who are already 3 months sober. 4
• The patient's 3-month sobriety milestone changes the clinical context: maintaining abstinence is now the priority, and psychosocial interventions combined with relapse-prevention pharmacotherapy (if needed) take precedence over buspirone. 1

Switch to SSRI for Anxiety Disorders

• Paroxetine or sertraline are first-line pharmacologic options for both social anxiety disorder and generalized anxiety disorder in patients with alcohol use disorder history. 5
• Start paroxetine 20 mg once daily (can increase to 40–60 mg) or sertraline 50 mg daily (titrate to 50–200 mg over 4–6 weeks). 1, 5
• SSRIs have demonstrated efficacy in comorbid anxiety and alcohol use disorders, though the evidence base is limited and of very low quality; paroxetine showed a risk ratio of 2.23 for global clinical response versus placebo in two small trials. 5
• Common pitfall: SSRIs require 4–6 weeks to achieve maximal anxiolytic effect, so counsel the patient about delayed onset and continue weekly psychosocial support during this transition. 5
• Monitor for sexual side effects (commonly reported with paroxetine and sertraline) and consider dose adjustment or switching agents if these emerge. 5

Address Gabapentin-Related Cognitive Complaints

Evaluate Gabapentin Dosing and Timing

• Gabapentin causes dose-dependent dizziness and sedation, which can manifest as subjective "forgetfulness." 1
• Obtain the current gabapentin dose and dosing schedule: if the patient is taking >1800 mg/day or taking large doses at bedtime, cognitive side effects are more likely. 1
• Consider redistributing the total daily dose (e.g., 300–600 mg three times daily rather than a single large evening dose) to minimize peak-related sedation. 1
• If cognitive complaints persist despite dose optimization, switch to a tricyclic antidepressant (TCA) for neuropathic pain, which will also address the comorbid depression. 1

Switch to Tricyclic Antidepressant if Gabapentin Intolerable

• Nortriptyline (a secondary-amine TCA) is first-line pharmacotherapy for peripheral neuropathy and has established efficacy in depression. 1
• Start nortriptyline 25 mg at bedtime; increase by 25 mg every 3–7 days as tolerated to a target of 75–150 mg/day. 1
• Obtain a screening electrocardiogram before initiation (recommended for patients >40 years) to rule out conduction abnormalities. 1
• Allow 6–8 weeks (including 2 weeks at maximum tolerated dose) for an adequate trial of TCA therapy. 1
• TCAs carry cardiac toxicity risk; prescribe with caution and limit dosages to <100 mg/day when possible, though this patient's age (40 years) and lack of known cardiac disease make nortriptyline a reasonable choice. 1

Essential Work-Up Before Medication Changes

Assess Liver Function and Alcohol Abstinence Status

• Obtain baseline liver function tests (AST, ALT, bilirubin, INR) before starting any new psychotropic medication, particularly SSRIs, to establish hepatic safety. 6
• Confirm continued abstinence through patient report and collateral history; consider urine ethyl glucuronide (EtG) testing if there is clinical suspicion of relapse. 1
• If liver enzymes are elevated or there is any evidence of alcoholic liver disease, avoid SSRIs and TCAs; instead, consider baclofen (10 mg three times daily, titrated to 30–80 mg/day) as the only medication with proven safety in cirrhosis. 6

Screen for Depression Severity

• Administer a validated depression scale (PHQ-9 or HAM-D) to quantify depressive symptoms, as the patient reports depression but is not currently on antidepressant therapy. 1
• If moderate-to-severe depression is present (PHQ-9 ≥10), an SSRI or TCA will address both anxiety and depression, making these agents particularly appropriate. 1, 5

Evaluate Cognitive Function Objectively

• Perform a brief cognitive screen (Montreal Cognitive Assessment [MoCA] or Mini-Mental State Examination) to distinguish medication-related sedation from alcohol-related cognitive impairment (e.g., Wernicke-Korsakoff syndrome, alcoholic dementia). 1
• If objective cognitive deficits are present, ensure the patient is receiving thiamine 100–300 mg daily (should have been initiated during early abstinence but may need continuation). 6
• Check vitamin B12, folate, and thyroid function to rule out reversible causes of cognitive impairment common in alcoholics. 1

Assess for Relapse Risk and Need for Abstinence Pharmacotherapy

• At 3 months of sobriety, the patient is at ongoing risk for relapse; psychosocial interventions (cognitive-behavioral therapy, motivational enhancement, 12-step facilitation) are mandatory and must be combined with any pharmacotherapy. 1, 6
• If the patient expresses cravings or has had near-miss relapse episodes, consider adding acamprosate 666 mg three times daily (safe in any degree of liver disease, no hepatotoxicity risk) to maintain abstinence. 6
• Do not prescribe naltrexone unless liver function tests are completely normal and there is no history of alcoholic liver disease; naltrexone is absolutely contraindicated in any hepatic dysfunction. 6

Specific Medication Algorithm

Step 1: Discontinue Buspirone

• Taper is not required for buspirone; it can be stopped abruptly without withdrawal syndrome. 7

Step 2: Initiate SSRI for Anxiety

• Start paroxetine 20 mg once daily (preferred for social anxiety disorder based on trial data) or sertraline 50 mg once daily (alternative with similar efficacy). 5
• Titrate paroxetine to 40 mg after 2 weeks if partial response; titrate sertraline by 50 mg every 1–2 weeks to a maximum of 200 mg/day. 1, 5
• Reassess anxiety symptoms at 4–6 weeks using a validated scale (GAD-7, Liebowitz Social Anxiety Scale). 5

Step 3: Optimize or Switch Neuropathy Treatment

• If gabapentin dose is >1800 mg/day, reduce to 600 mg three times daily and reassess cognitive complaints in 1–2 weeks. 1
• If cognitive complaints persist at optimized gabapentin dosing, switch to nortriptyline 25 mg at bedtime, titrating by 25 mg every 3–7 days to 75–150 mg/day. 1
• Monitor for anticholinergic side effects (dry mouth, constipation, urinary retention) and cardiac conduction changes. 1

Step 4: Reinforce Psychosocial Treatment

• Ensure the patient is engaged in weekly individual psychotherapy (cognitive-behavioral therapy or motivational enhancement) and group therapy (Alcoholics Anonymous or similar peer support). 1
• Psychosocial treatment is not optional; pharmacotherapy alone is insufficient for optimal outcomes in alcohol use disorder and comorbid psychiatric conditions. 1, 6

Common Pitfalls to Avoid

• Do not continue buspirone "to see if it works": the patient has already declared it ineffective and poorly tolerated after an adequate trial, and there is no evidence supporting its use in social phobia. 2, 3
• Do not attribute all cognitive complaints to gabapentin without objective testing: alcohol-related brain injury, thiamine deficiency, and depression can all cause subjective memory problems. 1
• Do not prescribe benzodiazepines for anxiety: although effective, they carry high abuse potential in patients with alcohol use disorder and should be reserved only for acute alcohol withdrawal (which this patient is not experiencing at 3 months sober). 1, 6
• Do not start naltrexone without confirming normal liver function: even mild transaminase elevation is a contraindication due to hepatotoxicity risk. 6
• Do not omit psychosocial interventions: combined pharmacotherapy and psychosocial treatment yields significantly better outcomes than medication alone (effect size 0.18–0.28). 6