Wellbutrin (Bupropion) for PMDD: Not Recommended
Bupropion should not be used for PMDD, as research demonstrates that non-serotonergic antidepressants, including bupropion, are ineffective for this condition. 1
Evidence Against Bupropion for PMDD
Direct Evidence of Ineffectiveness
- Bupropion has been specifically studied and found to be ineffective for premenstrual dysphoria, in contrast to serotonin reuptake inhibitors which show robust efficacy 1
- This finding is consistent with the pathophysiology of PMDD, which involves serotonergic dysfunction rather than dopaminergic or noradrenergic mechanisms that bupropion targets 1
First-Line Treatment: SSRIs
The evidence overwhelmingly supports selective serotonin reuptake inhibitors (SSRIs) as first-line treatment for PMDD:
- Sertraline (50-150 mg/day), fluoxetine (10-20 mg/day), escitalopram (10-20 mg/day), and paroxetine (12.5-25 mg/day) are established first-line treatments 2
- SSRIs reduce PMDD symptoms significantly more effectively than placebo, particularly psychological and behavioral symptoms 1, 3
- SSRIs have a uniquely rapid onset of action in PMDD (within days), much faster than their effect in depression or anxiety disorders 1
Dosing Strategy for SSRIs
- Intermittent (luteal phase only) SSRI therapy is effective and should be recommended before continuous daily dosing 3
- Intermittent administration may actually be superior to continuous dosing, possibly by avoiding tolerance development 1
- This allows women to take medication for only 14 days each month, improving adherence and reducing side effects 3
Alternative Treatments if SSRIs Fail
If SSRIs are ineffective or not tolerated:
- Drospirenone-containing oral contraceptives (3 mg drospirenone with 20 mcg ethinyl estradiol for 24 days, 4 days inactive) are considered first or second-line treatment 2
- Cognitive behavioral therapy (CBT) shows positive results in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict 2
- Other serotonergic agents like venlafaxine, duloxetine, alprazolam, and buspirone have demonstrated utility 4
Clinical Pitfall
The key mistake would be treating PMDD like major depressive disorder, where bupropion is an effective option. PMDD has distinct pathophysiology centered on serotonergic dysfunction in response to normal hormonal fluctuations 1, making serotonergic agents specifically effective while non-serotonergic antidepressants like bupropion fail 1.