What is an alternative or augmentation to sertraline (Selective Serotonin Reuptake Inhibitor) for a patient with Obsessive-Compulsive Disorder (OCD), Social Anxiety Disorder (SAD), and Generalized Anxiety Disorder (GAD), who is experiencing significant sexual dysfunction, emotional blunting, and fatigue?

Managing SSRI-Related Side Effects in OCD, Social Anxiety, and Generalized Anxiety Disorder

Primary Recommendation

Switch sertraline to bupropion or augment sertraline with bupropion to address sexual dysfunction, emotional blunting, and fatigue while maintaining therapeutic efficacy for anxiety disorders. 1

Rationale and Evidence-Based Approach

Sexual Dysfunction Profile of Antidepressants

The American College of Physicians guidelines clearly establish that bupropion is associated with significantly lower rates of sexual adverse events than fluoxetine and sertraline, while paroxetine has the highest rates of sexual dysfunction among SSRIs 1. This makes bupropion the optimal choice when sexual dysfunction is the primary concern affecting quality of life.

Treatment Strategy Options

Option 1: Augmentation with Bupropion (Preferred Initial Approach)

Augmenting sertraline with bupropion is supported by moderate-quality evidence showing lower discontinuation rates due to adverse events compared to buspirone augmentation 1. This strategy allows you to:

• Maintain the therapeutic benefits of sertraline for OCD (which requires SSRI therapy) 1, 2
• Address sexual dysfunction, emotional blunting, and fatigue through bupropion's dopaminergic and noradrenergic mechanisms 1, 3
• Avoid the risk of symptom recurrence that comes with complete medication switches

The STAR*D trial demonstrated that augmentation with bupropion SR showed similar efficacy to other augmentation strategies but with significantly better tolerability (12.5% discontinuation due to adverse events versus 20.6% with buspirone) 1.

Option 2: Switch to Alternative SSRI with Better Tolerability Profile

If augmentation is not feasible, switching to escitalopram may provide equivalent efficacy for all three anxiety disorders with potentially better tolerability 4. Escitalopram has demonstrated:

• Efficacy in panic disorder, GAD, social anxiety disorder, and OCD in multiple controlled trials 4
• Lower rates of sexual dysfunction compared to paroxetine and comparable to sertraline 1
• However, it will NOT address the sexual dysfunction, emotional blunting, or fatigue concerns as effectively as bupropion

Important caveat: Bupropion monotherapy is NOT recommended for OCD, as SSRIs remain the first-line pharmacological treatment with established efficacy 1. Bupropion lacks evidence for OCD treatment specifically.

Option 3: Complete Switch to Bupropion (Only for GAD and Social Anxiety)

If OCD symptoms are mild or in remission, switching entirely to bupropion is reasonable for GAD and social anxiety disorder 1. Moderate-quality evidence shows no difference in response rates when switching between second-generation antidepressants (bupropion vs. sertraline or venlafaxine) 1.

Critical limitation: This approach sacrifices OCD symptom control, as bupropion has no established efficacy for OCD 1.

Cognitive Behavioral Therapy Integration

Strongly consider adding CBT regardless of medication strategy, as moderate-quality evidence demonstrates CBT has similar efficacy to SSRIs with fewer adverse effects and lower relapse rates 1. For OCD specifically, CBT with exposure and response prevention shows larger effect sizes than pharmacotherapy (number needed to treat of 3 for CBT versus 5 for SSRIs) 1.

CBT augmentation allows for:

• Potential dose reduction of sertraline, which may decrease side effect burden 1
• Long-term symptom management with lower relapse risk 1
• Treatment of all three anxiety disorders simultaneously 1, 4

Practical Implementation Algorithm

1. First-line approach: Add bupropion SR 150 mg daily to current sertraline dose, titrate to 300 mg daily as tolerated 1

   • Monitor for seizure risk (bupropion contraindication) 1
   • Assess response at 4-6 weeks for sexual function and energy improvement

2. If augmentation fails or is not tolerated: Switch to escitalopram 10-20 mg daily 4

   • Taper sertraline while initiating escitalopram
   • Expect 8-12 weeks for full OCD response 1

3. Concurrent with either strategy: Initiate CBT with exposure and response prevention for OCD and cognitive therapy for GAD/social anxiety 1

Common Pitfalls to Avoid

• Do not switch to paroxetine, which has the highest rates of sexual dysfunction among all SSRIs 1
• Do not use bupropion monotherapy if OCD symptoms are active, as it lacks efficacy for OCD 1
• Do not discontinue sertraline abruptly when switching; taper to avoid discontinuation syndrome 1
• Do not assume all SSRIs have identical side effect profiles; individual variation exists but population-level differences are clinically meaningful 1

Monitoring Parameters

• Assess sexual function, emotional range, and energy levels at 4-6 weeks after bupropion initiation 1
• Monitor OCD symptoms using Yale-Brown Obsessive Compulsive Scale if switching medications 4
• Evaluate anxiety symptoms for GAD and social anxiety at 8-12 weeks 4
• Screen for treatment-emergent suicidal ideation, particularly in younger adults 1