What are the effects of increasing Selective Serotonin Reuptake Inhibitor (SSRI) dosage during Premenstrual Dysphoric Disorder (PMDD)?

From the Guidelines

Increasing the dose of SSRIs during the premenstrual phase can be an effective strategy for managing premenstrual disorders, and it is recommended to increase the dose as tolerated within the therapeutic dosage range in the smallest available increments at approximately 1- to 2-week intervals. When considering increasing the dose of SSRIs, such as fluoxetine, sertraline, or escitalopram, during the premenstrual phase, it is essential to carefully track the menstrual cycle to identify when symptoms typically begin, and then increase the SSRI dose 7-14 days before the expected period, and return to the baseline dose when menstruation begins 1. This approach allows for higher medication levels when symptoms are most severe while minimizing side effects during the rest of the month.

Key Considerations

• The dose increase should be done gradually, with careful monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1.
• Each SSRI has special prescribing considerations, such as the potential for discontinuation syndrome, drug-drug interactions, and QT prolongation associated with Torsade de Pointes, ventricular tachycardia, and sudden death 1.
• The choice of SSRI and the dose increase should be individualized based on the patient's symptoms, medical history, and response to treatment.

Implementation

• Start with a subtherapeutic dose as a “test” dose to assess for initial adverse effects, such as anxiety or agitation 1.
• Use standardized symptom rating scales to systematically assess treatment response and adjust the dose accordingly.
• Consider the potential for drug-drug interactions and monitor for symptoms, especially when concomitantly administering SSRIs with other medications that may interact with them 1.

From the Research

Increasing SSRI Dosage for Premenstrual Disorder

• The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in reducing premenstrual symptoms has been established in several studies 2, 3, 4, 5, 6.
• SSRIs can be taken either in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration 2.
• However, a more recent study suggests that SSRI treatment is probably more effective when administered continuously than when administered only in the luteal phase 3.
• The most common side effects associated with SSRIs are nausea, asthenia, somnolence, fatigue, decreased libido, and sweating 2, 3, 4.
• Adverse effects are dose-related, and the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event can be calculated 2.
• The overall quality of the evidence for the main findings is low to moderate, with the main weakness being poor reporting of methods 2, 3.

SSRI Dosage and Administration

• Intermittent SSRI therapy, where the drug is taken for only 14 days each month, has been found to be an effective treatment for premenstrual dysphoric disorder (PMDD) 4.
• Symptom-onset dosing with escitalopram, fluoxetine, and paroxetine controlled release (CR) is as effective as continuous or luteal phase dosing for some women 5.
• The wide range of clinical efficacy of SSRIs suggests that they exert their therapeutic effect through multiple pathways 5.

Clinical Evidence and Rationale

• The evidence indicates that SSRIs are effective in reducing premenstrual symptoms, particularly psychological or behavioral symptoms, during the luteal phase in women with PMDD 4.
• SSRIs have also been found to improve the quality of life in women with PMDD 4.
• Headache, fatigue, insomnia, and anxiety are often reported as adverse effects of SSRIs 4.
• A decrease in libido or sexual dysfunction is also a common adverse effect of SSRIs 4.