Treatment of PMDD with Buspirone and Sertraline
Yes, sertraline is an effective first-line treatment for PMDD, but buspirone should not be used as primary therapy for this condition. Sertraline has robust evidence supporting its efficacy in PMDD, while buspirone has only weak evidence showing mild benefit for premenstrual irritability specifically, not the full spectrum of PMDD symptoms 1, 2.
Evidence-Based Treatment Algorithm for PMDD
First-Line Pharmacological Treatment
Sertraline is a proven, effective treatment for PMDD and should be recommended. Multiple high-quality randomized controlled trials demonstrate that SSRIs, including sertraline, probably reduce overall premenstrual symptoms in women with PMDD (SMD -0.57,95% CI -0.72 to -0.42) 1.
Two dosing strategies are available for sertraline:
Luteal phase dosing (preferred for PMDD): Sertraline taken only during the luteal phase (from ovulation to menses) is FDA-approved for PMDD and offers the advantage of minimizing adverse effects while reducing medication burden 3. Clinical response occurs within several days of initiation, and no significant discontinuation effects occur with repeated cyclic stopping 3.
Continuous dosing: Daily administration throughout the menstrual cycle is probably more effective than luteal phase dosing (continuous: SMD -0.69 vs luteal: SMD -0.39; P = 0.03 for subgroup difference), though this comes with greater exposure to potential adverse effects 1.
Buspirone: Limited Role in PMDD
Buspirone should not be used as primary treatment for PMDD. While one randomized controlled trial found buspirone significantly superior to placebo for global improvement (P<0.001) and appeared to reduce self-rated irritability, it did not markedly improve other PMDD symptoms 2. The evidence characterizes buspirone as only "mildly effective for premenstrual irritability" 2.
The only potential role for buspirone in PMDD is as an alternative for patients who develop sexual dysfunction on SSRIs, as buspirone did not cause significantly more sexual dysfunction than placebo in the PMDD trial 2. However, this represents a second-line strategy after SSRI failure due to side effects, not a primary treatment approach.
Combination Therapy Considerations
There is no evidence supporting the combination of buspirone and sertraline for PMDD. The available literature does not evaluate this combination, and buspirone's mechanism (partial 5HT1A receptor agonist) does not provide additive benefit to sertraline's serotonin reuptake inhibition for the core symptoms of PMDD 2.
In depression treatment, augmentation of SSRIs with buspirone has been studied, but analyses show similar efficacy whether augmenting with buspirone or other strategies, with buspirone associated with higher discontinuation rates due to adverse events (20.6%) 4. This depression data should not be extrapolated to PMDD, which has a different pathophysiology involving luteal phase abnormalities in serotonergic activity and altered GABAA receptor configuration triggered by progesterone metabolites 5.
Important Adverse Effect Profile
Sertraline carries typical SSRI adverse effects that patients should be counseled about:
- Nausea (OR 3.30,95% CI 2.58 to 4.21) 1
- Sexual dysfunction or decreased libido (OR 2.32,95% CI 1.57 to 3.42) 1
- Insomnia (OR 1.99,95% CI 1.51 to 2.63) 1
- Asthenia/decreased energy (OR 3.28,95% CI 2.16 to 4.98) 1
- Somnolence and decreased concentration (OR 3.26,95% CI 2.01 to 5.30) 1
Sexual dysfunction is a particularly important consideration, as sertraline causes sexual dysfunction in approximately 14% of males and 6% of females based on depression studies 6. If sexual dysfunction becomes problematic on sertraline, buspirone could be considered as an alternative since it does not significantly increase sexual dysfunction compared to placebo 2.
Contraception Considerations
If the patient requires contraception, combined hormonal contraceptives may provide dual benefit. Specifically, 20 mcg ethinyl estradiol/3mg drospirenone in a 24/4 extended cycle regimen has been shown to significantly improve emotional and physical symptoms of PMDD 5. This could potentially reduce or eliminate the need for sertraline.
Avoid progestin-only contraceptive methods in PMDD patients, as progestin-only pills, levonorgestrel IUDs, etonorgestrel implants, and depot medroxyprogesterone acetate have the potential to negatively affect mood symptoms in women with PMDD 5.
Clinical Pitfalls to Avoid
- Do not use buspirone as monotherapy for PMDD unless the patient has failed or cannot tolerate SSRIs due to sexual dysfunction 2
- Do not combine buspirone with sertraline without clear rationale, as there is no evidence supporting this combination and it increases polypharmacy burden
- Monitor for serotonin syndrome if multiple serotonergic agents are used, though this is rare with monotherapy 4
- Ensure proper diagnosis with prospective symptom charting showing luteal phase symptoms that resolve after menses onset, as retrospective diagnosis is unreliable 1, 5