What is the recommended treatment for a female patient of reproductive age with premenstrual dysphoric disorder (PMDD) and a potential history of bipolar disorder?

Treatment of Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD, with fluoxetine 20 mg/day, sertraline 50-150 mg/day, escitalopram 10-20 mg/day, or paroxetine 12.5-25 mg/day administered either continuously or during the luteal phase only. 1, 2, 3, 4

Critical Consideration: History of Bipolar Disorder

SSRIs must be avoided in patients with a history of bipolar disorder due to the risk of precipitating mania. 5 This is a critical contraindication that fundamentally changes the treatment approach for this patient population.

Alternative Treatment Algorithm for PMDD with Bipolar History

For patients with PMDD and potential bipolar disorder, combined hormonal contraceptives containing 20 mcg ethinyl estradiol/3 mg drospirenone in a 24/4 extended cycle regimen should be the first-line treatment. 6 This approach addresses PMDD symptoms while avoiding the mood destabilization risk associated with SSRIs.

Step 1: Confirm Bipolar Diagnosis

• Obtain detailed psychiatric history including family history of bipolar disorder, suicide, and depression 1
• Screen for prior manic/hypomanic episodes, rapid mood cycling, or antidepressant-induced mood elevation 1
• Document any history of mood destabilization with previous SSRI trials 5

Step 2: Initiate Hormonal Treatment

• Start drospirenone/ethinyl estradiol 3 mg/20 mcg in 24/4 extended cycle regimen 6
• This formulation has demonstrated significant improvement in both emotional and physical PMDD symptoms 6
• Monophasic extended-cycle formulations with less androgenic progestins may also be effective 6

Step 3: Avoid Progestin-Only Methods

• Do not use progestin-only pills, levonorgestrel IUD, etonorgestrel implant, or depot medroxyprogesterone acetate 6
• These methods can negatively affect mood symptoms in women with baseline mood disorders including PMDD 6
• Copper IUD is recommended only for patients not seeking hormonal contraception 6

Step 4: Consider Calcium Supplementation

• Add calcium supplementation as adjunctive therapy 4
• Calcium is the only supplement with consistent demonstrated therapeutic benefit for PMDD 4

Standard SSRI Treatment Protocol (For Patients WITHOUT Bipolar History)

Medication Selection and Dosing

Continuous dosing is more effective than luteal-phase-only administration (SMD -0.69 vs -0.39, P = 0.03 for subgroup difference). 2

First-Line SSRI Options:

• Fluoxetine: 10-20 mg/day 1, 3
• Sertraline: 50-150 mg/day 2, 3
• Escitalopram: 10-20 mg/day 3
• Paroxetine: 12.5-25 mg/day 3

Luteal Phase Dosing Alternative:

• Administer SSRI 3-6 hours before anticipated symptom onset or beginning 14 days before expected menses 7
• Continue through onset of menstruation 7
• Less effective than continuous dosing but may be preferred by some patients 2, 7

Expected Adverse Effects and Management

Patients must be counseled about common SSRI adverse effects before initiating treatment:

• Nausea: OR 3.30 (most common adverse effect) 2
• Sexual dysfunction/decreased libido: OR 2.32 2
• Insomnia: OR 1.99 2
• Asthenia/decreased energy: OR 3.28 2
• Somnolence/decreased concentration: OR 3.26 2
• Dizziness/vertigo: OR 1.96 2
• Dry mouth: OR 2.70 2
• Diarrhea: OR 2.06 2
• Sweating: OR 2.17 2
• Tremor: OR 5.38 2
• Fatigue/sedation: OR 1.52 2
• Constipation: OR 2.39 2

Monitoring Requirements

• Screen for suicidality at baseline and monitor closely during initial months of treatment 1
• Assess for agitation, irritability, unusual behavioral changes, anxiety, panic attacks, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania 1
• These symptoms may represent precursors to emerging suicidality or mood destabilization 1
• Monitor daily during first weeks, then weekly for first month, then monthly 1

Treatment Response Timeline

• Initial symptom reduction: Expect within 2-4 weeks 2
• Maximal therapeutic benefit: Achieved by 8-12 weeks 2
• Adequate trial duration: Minimum 8 weeks at therapeutic dose before concluding treatment failure 2, 4

Cognitive Behavioral Therapy as Adjunctive Treatment

CBT demonstrates effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict associated with PMDD. 3

• CBT reduces: functional impairment, depressed mood, hopelessness, anxiety, mood swings, sensitivity, irritability, insomnia, interpersonal conflict, and symptom handicap 3
• Can be used as monotherapy or combined with pharmacotherapy 3, 4
• Particularly valuable for patients who cannot tolerate or refuse medication 3

Alternative Pharmacological Options

Second-Line Treatments (If SSRIs Fail or Are Contraindicated):

• Venlafaxine (SNRI): Demonstrated efficacy for PMDD 4
• Duloxetine (SNRI): Effective alternative 4
• Alprazolam: Useful for anxiety-predominant symptoms 4
• Buspirone: May reduce anxiety symptoms 4

Anovulatory Treatments:

• Drospirenone-containing combined oral contraceptives (as described above) 6, 3
• GnRH agonists with add-back therapy (limited by side effects and cost) 4

Common Pitfalls to Avoid

• Never prescribe SSRIs without screening for bipolar disorder history 5, 1
• Avoid abrupt SSRI discontinuation - taper gradually to prevent withdrawal syndrome 5
• Do not use progestin-only contraceptives in patients with mood disorders 6
• Do not prescribe antidepressants for the smallest quantity to reduce overdose risk 1
• Do not assume amenorrhea equals infertility - contraception counseling remains necessary 6
• Avoid underdosing - ensure therapeutic doses are achieved before concluding treatment failure 2, 4
• Do not combine multiple serotonergic agents without monitoring for serotonin syndrome 1

Treatment Discontinuation

• If discontinuing SSRI treatment, taper medication as rapidly as feasible while recognizing abrupt discontinuation risks 1
• Withdrawal symptoms may include anxiety, agitation, dizziness, and mood changes 5
• Close monitoring required during discontinuation period 1