Management of PMDD Not Responding to SSRI or Yaz COCP
For patients with Premenstrual Dysphoric Disorder (PMDD) not responding to SSRIs or Yaz COCP, tricyclic antidepressants (TCAs) such as amitriptyline are recommended as the next treatment option.
Second-Line Treatment Options
Tricyclic Antidepressants (TCAs)
- Amitriptyline is suggested as an effective second-line option for PMDD patients who have failed SSRI therapy 1
- Dosing recommendation: 10-100 mg orally at night 1
- TCAs have been shown to provide global symptom relief with a relative risk of 0.67 (95% CI, 0.54-0.82) compared to placebo 1
- Particularly effective for addressing mood lability, anxiety, and irritability symptoms
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
- Venlafaxine and duloxetine can be considered when SSRIs have failed
- SNRIs are slightly more effective than SSRIs for depression symptoms, though with higher rates of adverse effects such as nausea and vomiting 1
- May be particularly helpful for patients with comorbid pain symptoms
Adjunctive Therapies
Quetiapine
- Adjunctive quetiapine SR (sustained-release) has shown promise in a small double-blind study for patients with inadequate response to SSRI/SNRI therapy 2
- Starting dose of 25 mg during the luteal phase
- Demonstrated improvement in mood lability, anxiety, and irritability symptoms
- Consider for patients with prominent mood instability
Other Hormonal Options
- Consider continuous use (without a break) of combined hormonal contraceptives if Yaz has failed 1
- Note: Combined hormonal contraceptives are contraindicated in women with migraine with aura due to increased stroke risk 1
Perimenstrual Preventive Treatment
- Long-acting NSAIDs (e.g., naproxen) for 5 days beginning 2 days before expected menstruation 1
- Long-acting triptans (e.g., frovatriptan, naratriptan) using the same schedule 1
Non-Pharmacological Approaches
Cognitive Behavioral Therapy (CBT)
- Effective in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict with others 3
- Helps develop coping strategies for symptom management
- Should be considered alongside pharmacological treatment
Calcium Supplementation
- Among supplements, calcium has demonstrated the most consistent therapeutic benefit 4
- Can be used as an adjunctive treatment alongside medication
Treatment Algorithm
- First attempt: SSRI (sertraline, fluoxetine, escitalopram, paroxetine) or Yaz COCP
- If no response:
- Switch to a TCA (amitriptyline 10-100 mg at night)
- OR try an SNRI (venlafaxine, duloxetine)
- If partial response:
- Consider adjunctive quetiapine SR (25 mg during luteal phase)
- Add perimenstrual preventive treatment with NSAIDs or triptans
- For all patients:
- Add CBT to address psychological symptoms
- Consider calcium supplementation
Monitoring and Follow-up
- Evaluate treatment response within 2-3 months after initiation or change in treatment 1
- Use headache/symptom calendars to track symptoms on symptomatic days
- Monitor for adverse effects of TCAs, which may include dry mouth, constipation, sedation, and weight gain
- Assess for improvement in functional impairment and quality of life, not just symptom reduction
Cautions and Considerations
- TCAs are contraindicated in patients with heart failure, glaucoma, and when co-administered with monoamine oxidase inhibitors or SSRIs 1
- Approximately 40% of women with PMDD do not respond to SSRIs, highlighting the need for alternative approaches 5
- Be aware of potential drug interactions, especially when combining multiple psychotropic medications
- TCAs should be used cautiously in patients with suicidal ideation due to potential lethality in overdose
By following this structured approach to treatment-resistant PMDD, clinicians can help patients achieve better symptom control and improved quality of life.