What is the treatment for cyclic vomiting syndrome (CVS) associated with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD)?

Treatment of Premenstrual Vomiting

For vomiting occurring exclusively before menses, start with an SSRI (selective serotonin reuptake inhibitor) in luteal-phase dosing as first-line therapy, as this addresses the underlying hormonal-serotonergic dysregulation that triggers premenstrual symptoms. 1, 2

Understanding the Clinical Pattern

This presentation represents either severe premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) with prominent gastrointestinal manifestations. The key diagnostic feature is the stereotypical timing—symptoms occur only during the luteal phase (after ovulation, before menses) and resolve with menstrual onset. 2, 3

Hormonal fluctuations during the luteal phase trigger abnormal serotonergic activity, which explains both the mood symptoms and gastrointestinal manifestations including nausea and vomiting. 2

First-Line Treatment: SSRIs

Begin with sertraline 50-150 mg daily, fluoxetine 20 mg daily, or paroxetine 12.5-25 mg daily, using luteal-phase-only dosing (starting 14 days before expected menses and stopping at menstrual onset). 1, 4, 3

Why SSRIs Work

• SSRIs directly address the serotonergic dysfunction that underlies premenstrual symptoms 1, 3
• Unlike depression treatment, SSRIs for PMDD work rapidly—within days—and can be dosed intermittently 4, 3
• Luteal-phase-only dosing is as effective as continuous dosing for most patients and minimizes medication exposure 1, 4

Dosing Strategy

• Start medication 14 days before expected menses (at ovulation) 4
• Continue through the first day of menstrual flow 4
• Symptom-onset dosing (starting when symptoms begin) is an alternative for patients with predictable prodromal symptoms 1

Second-Line Treatment: Hormonal Suppression

If SSRIs fail or are not tolerated, use combined oral contraceptives with continuous or extended-cycle dosing to suppress ovulation and eliminate hormonal fluctuations. 2, 3

Specific Hormonal Options

• Combined oral contraceptives: Use continuous dosing (skipping placebo weeks) to prevent hormonal cycling 2, 3
• GnRH agonists with add-back estrogen: For refractory cases, goserelin 3.6 mg subcutaneously monthly plus oral estradiol effectively suppresses ovulation and prevents recurrence 5
  • This approach is particularly effective for menstrually-triggered cyclic vomiting syndrome 5
  • Requires estrogen add-back to prevent bone loss and menopausal symptoms 5

Acute Symptom Management

During active vomiting episodes, use ondansetron 4-8 mg sublingual or promethazine 25 mg rectal suppository for immediate symptom control. 6

Abortive Therapy Approach

• Ondansetron sublingual tablets bypass the need for oral absorption during active vomiting 6
• Promethazine suppositories provide both antiemetic and sedating effects 6
• Consider adding lorazepam 0.5-1 mg sublingual for anxiety-related nausea that often accompanies premenstrual symptoms 6, 7

Important Clinical Distinctions

If vomiting episodes last hours to days with complete wellness between episodes, consider cyclic vomiting syndrome (CVS) triggered by menstruation rather than simple premenstrual vomiting. 6, 5

CVS Triggered by Menstruation

• Menstrual periods are a recognized trigger for CVS episodes 6
• These patients require both CVS-specific prophylaxis (tricyclic antidepressants like amitriptyline 25-150 mg nightly) AND hormonal suppression 6, 5
• One case report demonstrated complete resolution with GnRH agonist therapy for 4 months, with sustained remission for 5 years even after resuming normal menstruation 5

Treatment Algorithm

1. Confirm timing: Document symptoms occur only in luteal phase using a 2-month prospective symptom calendar 4

2. Start SSRI luteal-phase dosing: Sertraline 50 mg or fluoxetine 20 mg starting 14 days before menses 1, 4

3. If inadequate response after 2-3 cycles: Increase SSRI dose or switch to continuous daily dosing 1

4. If SSRI failure: Add or switch to continuous oral contraceptives 2, 3

5. For refractory cases: Consider GnRH agonist with estrogen add-back, particularly if pattern suggests menstrually-triggered CVS 5

Common Pitfalls to Avoid

• Do not treat with standard antiemetics alone—this addresses symptoms but not the underlying hormonal-serotonergic cause 1, 2
• Do not use cyclic oral contraceptives—the placebo week perpetuates hormonal fluctuations; use continuous or extended-cycle dosing instead 2, 3
• Do not delay SSRI trial—these are first-line with the strongest evidence base 1, 4, 3
• Do not assume this is gastroparesis or other GI disorder—the stereotypical menstrual timing is pathognomonic for hormonal etiology 2, 4

Adjunctive Measures

• Calcium supplementation 1200 mg daily has demonstrated consistent benefit for premenstrual symptoms 1, 3
• Cognitive behavioral therapy can reduce symptom severity and improve coping 2
• Avoid known triggers during the luteal phase: sleep deprivation, excessive stress, and caffeine 6