What is the recommended treatment approach for a patient with anxiety considering gabapentin and Wellbutrin (bupropion)?

Treatment Approach for Anxiety: Gabapentin and Wellbutrin

Neither gabapentin nor Wellbutrin (bupropion) should be used as first-line treatment for anxiety disorders. Bupropion is activating and can exacerbate anxiety, while gabapentin lacks robust evidence for anxiety treatment and carries significant risks of dependence and withdrawal.

First-Line Treatment Recommendations

For generalized anxiety disorder and social anxiety disorder, SSRIs (escitalopram, sertraline, paroxetine, fluvoxamine) or SNRIs (venlafaxine) are the recommended first-line pharmacotherapy options 1. These agents have demonstrated efficacy with acceptable tolerability profiles in treating anxiety symptoms 1.

• The Canadian Clinical Practice Guideline lists SSRIs and SNRIs as first-line drugs, with pregabalin also included, while gabapentin is relegated to second-line status 1
• Treatment requires 4-8 weeks for full therapeutic effect 1
• Multiple international guidelines (NICE, S3, Canadian CPG) consistently prioritize SSRIs/SNRIs over other agents 1

Why Bupropion Is Problematic for Anxiety

Bupropion is explicitly contraindicated in agitated patients and should not be used when anxiety is the primary concern 1.

• Bupropion is described as "activating" and can cause rapid improvement in energy levels, but this activation profile makes it unsuitable for anxious patients 1
• While bupropion is the only antidepressant consistently promoting weight loss 1, it can exacerbate anxiety symptoms 1
• When used in depression with comorbid anxiety, studies show no difference between bupropion and other antidepressants for treating the anxiety component 1
• The medication is specifically noted to be inappropriate for patients with anxiety disorders 1

Why Gabapentin Is Not Recommended

Gabapentin lacks high-quality evidence for anxiety treatment and carries substantial risks that outweigh potential benefits 2.

Evidence Limitations:

• No randomized controlled trials exist for gabapentin in generalized anxiety disorder 3
• One placebo-controlled study in panic disorder showed no overall drug/placebo difference (p=0.606), with benefit only in post-hoc analysis of severely ill patients 4
• Evidence is limited to case reports and small studies 3
• Gabapentin is listed only as a second-line agent in Canadian guidelines, not first-line 1

Safety Concerns:

• Gabapentin carries risks of tolerance, dependence, addiction, and withdrawal similar to benzodiazepines 2
• Deaths involving pregabalin (a related gabapentinoid) now exceed those from diazepam, fentanyl, tricyclics, or SSRIs as groups 2
• Case reports document delirium, intense cravings, and prolonged post-withdrawal confusional states reminiscent of benzodiazepine withdrawal 5
• The medication was scheduled as a class C controlled drug in 2019 due to abuse potential 2
• Short-term trials show only marginal differences from placebo and don't account for long-term tolerance and dependence 2

Limited Appropriate Use:

• When gabapentinoids are used perioperatively for opioid-sparing analgesia, they should be limited to a single lowest preoperative dose to avoid sedative side effects 1
• Doses must be adjusted for elderly patients and those with renal dysfunction 1

Recommended Treatment Algorithm

Step 1: Initiate SSRI (escitalopram or sertraline preferred) or SNRI (venlafaxine) as first-line pharmacotherapy 1

Step 2: Combine with cognitive behavioral therapy (CBT) for optimal outcomes, as CBT specifically developed for anxiety disorders shows efficacy 1

Step 3: If inadequate response after 4-8 weeks at therapeutic doses, switch to another SSRI or SNRI rather than adding gabapentin or bupropion 1

Step 4: For treatment-resistant cases, consider augmentation strategies with evidence-based agents, but avoid gabapentin due to dependence risks 2

Critical Caveats

• Avoid benzodiazepines for long-term anxiety management due to similar dependence issues as gabapentinoids 1, 2
• Preoperative education and non-pharmacologic anxiolysis should be prioritized over sedative medications 1
• NICE has been called upon to re-evaluate support for pregabalin in anxiety given known harms, which extends concerns to gabapentin 2
• Off-label use of gabapentinoids for psychiatric conditions requires reconsideration given lack of long-term efficacy and safety data 2