What can be prescribed for a 44-year-old female with first episode Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) who is concerned about low libido?

Prescribing for First-Episode MDD and GAD with Low Libido Concerns

Bupropion is the optimal first-line antidepressant choice for this patient, as it effectively treats both MDD and GAD while having minimal to no sexual side effects, unlike SSRIs which cause sexual dysfunction in 41-63% of patients. 1, 2, 3

Rationale for Bupropion as First-Line

Sexual Function Profile

• Bupropion causes sexual dysfunction in only 7-15% of patients compared to 41-63% with SSRIs like sertraline, making it the clear choice when libido is a primary concern 3
• Sexual dysfunction with SSRIs appears as early as day 7 of treatment at starting doses (50 mg/day sertraline) and persists throughout treatment 3
• The mechanism differs from SSRIs—bupropion is a dopamine-norepinephrine reuptake inhibitor rather than affecting serotonin, which accounts for its favorable sexual side effect profile 1, 2

Efficacy for MDD and GAD

• The American College of Physicians guidelines establish that all second-generation antidepressants, including bupropion, have equivalent efficacy for treating MDD with no clinically significant differences 4
• Bupropion demonstrates similar efficacy to SSRIs (escitalopram) and SNRIs (venlafaxine) in head-to-head trials for depression 1, 2
• While escitalopram has FDA approval specifically for GAD 5, bupropion effectively treats anxiety symptoms in the context of MDD and is commonly used for comorbid anxiety-depression presentations 6

Prescribing Algorithm

Initial Dosing

• Start with bupropion SR 150 mg once daily in the morning 2, 6
• After 3-4 days, increase to bupropion SR 150 mg twice daily (total 300 mg/day) if tolerated 2
• Alternative: Bupropion XL 150 mg once daily, increasing to 300 mg once daily after one week for improved adherence 1, 2

Monitoring Schedule

• Assess within 1-2 weeks of initiation for adverse effects and early therapeutic response per American College of Physicians guidelines 4, 7
• Continue regular monitoring every 2-4 weeks during acute phase
• If inadequate response by 6-8 weeks, modify treatment 4

Target Dose and Duration

• Therapeutic range: 300-450 mg/day (maximum 450 mg/day) 2, 6
• Continue for 4-9 months after achieving remission for first episode MDD 4
• Longer duration may be needed if she develops recurrent episodes 4

Alternative Strategy if Bupropion Fails or Is Contraindicated

Second-Line: SSRI with Planned Augmentation

If bupropion is ineffective or contraindicated (seizure history, eating disorder):

• Start escitalopram 10 mg daily, which has FDA approval for both MDD and GAD 5
• Escitalopram showed small statistical superiority over other SSRIs in meta-analysis, though clinical significance is debatable 4
• If sexual dysfunction emerges, add bupropion SR 150 mg daily or twice daily to reverse SSRI-induced sexual side effects 8
• This combination strategy is well-tolerated and effective for both enhancing antidepressant response and ameliorating sexual dysfunction 8

Critical Caveats

Bupropion-Specific Warnings

• Contraindicated in patients with seizure disorders, eating disorders (anorexia/bulimia), or abrupt discontinuation of alcohol/benzodiazepines due to lowered seizure threshold 2, 6
• Screen specifically for these conditions before prescribing
• Associated with less somnolence and weight gain compared to SSRIs and TCAs 1, 2

Universal Antidepressant Monitoring

• All second-generation antidepressants carry FDA warnings for increased suicidal thinking, particularly in the first 1-2 months, with highest risk in patients under 24 years (though this patient is 44) 7
• Monitor closely for worsening depression, agitation, or suicidal ideation at each visit 4, 7

Sexual Dysfunction Management

• If sexual dysfunction occurs with any antidepressant, it typically persists throughout treatment rather than resolving spontaneously 3
• Do not wait to address sexual side effects—they are a leading cause of treatment discontinuation and non-adherence 3
• Switching to bupropion or adding bupropion to existing SSRI therapy are both evidence-based approaches 3, 8

Why Not Other Options

• SSRIs (escitalopram, sertraline, paroxetine): While effective for both MDD and GAD 4, 5, they cause unacceptable rates of sexual dysfunction (41-63%) in a patient already concerned about low libido 3
• SNRIs (venlafaxine, duloxetine): Similar sexual side effect profile to SSRIs without clear advantage 4
• Mirtazapine: Faster onset of action but associated with significant sedation and weight gain 4

The evidence strongly supports bupropion as the optimal initial choice, balancing efficacy for both conditions with preservation of sexual function—the patient's primary concern 1, 2, 6, 3.