Challenges in recruiting women to postpartum depression (PPD) antidepressant treatment trials, which we encountered when conducting a trial of escitalopram, contribute to the limited body of knowledge about PPD treatment. Here we discuss results from a preliminary trial of escitalopram for PPD, and challenges of research in this area.
Escitalopram, the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with high selectivity and potency that is FDA-approved for treating major depressive disorder (MDD) and generalized anxiety disorder. An agent with antidepressant and anxiolytic effects is particularly desirable for PPD because anxiety is more common in postpartum major depressive episodes than non-postpartum MDD.1 Anxiety and depressive disorders commonly are comorbid in postpartum women.2
We conducted an open-label trial of escitalopram for women with PPD and anxiety. We initially attempted to recruit 20 women.
Methods
Patients received 8 weeks of treatment with escitalopram, 10 to 20 mg/d (flexible dose). After completing the initial phone screen, patients had 5 follow-up visits, once every 2 weeks for 8 weeks. The institutional review board at Massachusetts General Hospital approved this study and we obtained written informed consent from all patients at the first visit. Twelve patients completed the phone screen and 7 eligible patients were enrolled in the study over 32 months. Reasons for ineligibility included having a history of psychosis, onset of symptoms >3 months postpartum, or presenting >6 months after onset. Others declined to participate because of concern about the time commitment or because they pursued nonpharmacologic treatments after the evaluation visit. One patient was lost to follow-up. Three patients completed the study. The study was halted because of the slow pace of recruitment.
Patient selection. Patients were screened for a major depressive episode with postpartum onset within 3 months of childbirth; depressive symptoms may have developed during pregnancy and worsened postpartum to meet criteria for MDD. Women were eligible for the study if they:
- were age 18 to 45
- experienced a major depressive episode with symptoms developing within 3 months of childbirth
- presented within 6 months of childbirth
- had a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15
- had a Beck Anxiety Inventory (BAI) score >10.
Patients who were pregnant or breast-feeding were excluded from the study per an agreement with the sponsor. In addition, women were excluded if they had taken any psychotropic medication within 2 weeks of enrollment; had active suicidal ideation, homicidal ideation, or presence of psychotic symptoms; had chronic depression or dysthymia; had chronic or treatment-resistant anxiety disorders; had a history of mania or hypomania; or had active alcohol or substance abuse within the past year.
Treatment. Patients received escitalopram, 10 mg/d, after the baseline visit. At the investigator’s discretion, the dose could be increased to 20 mg/d or lowered to 5 mg/d if side effects occurred.
Measures. At the first visit, patients were assessed with the Mini-International Neuropsychiatric Interview to verify MDD and exclude diagnoses that would determine ineligibility. MADRS and Edinburgh Postnatal Depression Scale (EPDS) were used at each visit to measure depressive symptoms.3,4 The BAI was completed at each visit to measure anxiety symptoms. Obsessions and compulsions were measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)5 at baseline, and at all following visits if the patient scored >8 at baseline. The Clinical Global Impression Scales for severity and improvement were completed at each visit.6
Results
Of 7 patients enrolled, 3 completed the study, 2 were ineligible after the baseline visit, and 2 did not participate after the baseline visit (1 selected to pursue psychotherapy, and 1 was lost to follow-up).
Two of 3 patients responded to escitalopram (≥50% decrease on MADRS), and both were remitters (MADRS score <7). All 3 patients were responders on EPDS and BAI. One patient had Y-BOCS >8 at baseline (Total Y-BOCS score of 9, and final Y-BOCS score of 8) (Table).
Table
Symptom rating scale scores at baseline and study end
| Baseline (Visit 1) | Final (Visit 5) | |||||
|---|---|---|---|---|---|---|
| Patient | MADRS | BAI | EPDS | MADRS | BAI | EPDS |
| Ms. A | 21 | 18 | 22 | 12 | 0 | 0 |
| Ms. B | 28 | 28 | 19 | 4 | 5 | 2 |
| Ms. C | 37 | 6 | 19 | 6 | 2 | 0 |
| BAI: Beck Anxiety Inventory; EPDS: Edinburgh Postnatal Depression Scale; MADRS: Montgomery-Åsberg Depression Rating Scale | ||||||
Discussion
Patients who stayed in treatment improved during the course of this study. Recruitment was difficult; we were able to recruit only 7 patients out of a projected 20 for the screening visit. We solicited feedback from local obstetrics health care providers and social workers on recruitment and attractiveness of the study as part of our routine collaboration with obstetrical services that screen for PPD. Primary reasons patients were not referred were that they were breast-feeding or they stated they would prefer to receive treatment from their primary care doctor. Recruitment difficulty in this study was in stark contrast to other recent studies completed at our center. For example, we have successfully recruited for menopausal depression and premenstrual dysphoric disorder treatment studies, and have completed large naturalistic studies of women with unipolar depression and bipolar disorder across pregnancy and postpartum. We suspect that many patients who were eligible for the study preferred to seek care from an obstetrician or primary care doctor with whom they already had a therapeutic alliance, and we also suspect that many women with PPD do not seek treatment at all, which is consistent with findings from other research groups.