ABSTRACTObjectivesPrior studies have raised concerns about postpartum hemorrhage (PPH) risk associated with selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRIs and SNRIs), although limitations include possible confounding by maternal indications. The current study examined the risk of PPH associated with prenatal S/NRIs accounting for diagnosed maternal depression during pregnancy.MethodsThe current study is a secondary analysis of data from a cohort of 2213 pregnancies (1997–2010) identified from a large electronic medical record‐linkage system. Exposures were identified from electronic prescriptions records and resulted in three main groups: S/NRI‐exposed pregnancies (S/NRI users), antidepressant‐unexposed pregnancies (non‐users), and S/NRI exposure in the year prior to (but not during) pregnancy (former users). Data used to identify PPH occurrences included obstetrician chart diagnoses, diagnosis codes, and recorded estimated blood loss (EBL). The risk of PPH by exposure group was estimated using unadjusted, minimally adjusted (maternal age at delivery, delivery year, parity, and maternal smoking), and depression‐adjusted models (previous covariates and maternal depression). Supplemental analyses included an examination of PPH risk with prenatal bupropion monotherapy.ResultsThe study cohort consisted of 837 S/NRI users, 401 former users, and 786 non‐users, as well as 114 bupropion users identified for additional analyses. The frequency of PPH was 11.6% in the overall cohort, and was 14.7% for S/NRI users, 10.2% for former users, and 8.7% for non‐users. The risk of PPH was significantly higher for S/NRI users than non‐users in unadjusted (OR 1.82 [95% CI 1.33, 2.49]), minimally adjusted (aOR 1.66 [1.19, 2.31]), and depression‐adjusted models (aOR 1.46 [1.02, 2.10]). The risk of PPH was also higher for S/NRI former users than non‐users in unadjusted models (OR 1.54 [1.05, 2.26]) but not minimally adjusted (aOR 1.42 [0.95, 2.11]) or depression‐adjusted models (aOR 1.41 [0.95, 2.10]). No significant differences in PPH risk were observed between S/NRI users and former users, between bupropion users and non‐users, or between S/NRI users and bupropion users.ConclusionsPrenatal S/NRI exposure was associated with an increased risk of PPH after adjusting for maternal depression, although residual confounding and confounding by other factors (including unmeasured factors) may be possible, as the risk of PPH appeared to be similar between S/NRI users and former users. Best‐practice PPH risk management strategies should be adhered to for depressed patients, especially those who require treatment with antidepressants during pregnancy.
Developing a Decision Support Tool to Guide Shared Decision‐Making in Bipolar Depression Treatment: Results From a Collaboration Between Clinicians and People With Lived Experience
ABSTRACTObjectiveTo build consensus from different stakeholders on the content and digital interactivity of a shared decision making (SDM) tool to guide patient‐clinician collaborative conversations about treatment for bipolar depression.Patients and MethodsThis study was conducted between September 2022 and September 2023. In the first phase, we conducted a narrative review on pharmacological, neuromodulatory, and psychotherapeutic treatments available for bipolar depression. For each option, we assessed treatment effectiveness, side effects, need for clinical monitoring, clinical considerations, and cost. In the second phase, committees comprised of mental health clinicians and people with lived experience with bipolar disorder from a national mood disorders advocacy group identified key features and content to be included in the SDM tool. A thematic analysis of these data then contributed to populate the SDM tool.ResultsTwenty‐one evidence‐based treatment options identified from the narrative review were presented to the four convened committees (clinical, lived experience, peer council, and integrated steering committees) in five meetings. After discussions and thematic analysis, 12 outcomes of interest for each of the therapeutic interventions were delineated for inclusion in a web‐based SDM tool. A detailed description of the development process and SDM tool is provided.ConclusionThis is the first partnership between clinicians and persons with bipolar disorder lived experience charged with the development of a patient‐centered SDM tool to integrate clinical evidence with real‐world clinical practice and patient preferences for use during clinical encounters. Human‐centered design and testing in real clinical encounters will now contribute to refining the instrument and readying it for rigorous evaluation and implementation in practice.
Association of Optimal Lamotrigine Serum Levels and Therapeutic Efficacy in Mood Disorders
Abstract Purpose The aim of the study was to appraise the current evidence on the optimal serum level for lamotrigine (LAM) in the treatment of mood disorders (major depressive disorder, bipolar disorder). Methods Major databases were searched for randomized controlled trials, open-label trials, and observational studies reporting serum LAM levels in adult patients treated with LAM for mood disorders. Results A total of 814 abstracts were screened and 24 articles were selected for full-text review. Seven studies (226 bipolar disorder and 17 major depressive disorder patients) including 1 randomized controlled trial (n = 43), 3 prospective (n = 53), and 3 retrospective (n = 147) studies met the study criteria with a study duration range from 6 to 96 weeks. Lamotrigine daily dosage varied from 25 to 425 mg/d among the studies. Studies reported inconsistent findings between LAM concentration and efficacy. Three studies did not identify a relationship between LAM levels and a significant improvement in mood symptoms. Two studies (n = 99) reported higher response rates with LAM serum levels of greater than 3.25 μg/mL and 1 study (n = 25) reported a wide therapeutic window of 5 to 11 μg/mL. Overall, LAM was well tolerated with no major significant adverse effects. Conclusions Most studies showed a minimum LAM threshold level of 3 μg/mL in patients with mood disorders; however, the data are inconsistent regarding the therapeutic range for LAM. Based on the pooled data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM serum levels for mood improvement. Further studies including larger sample sizes are required to address this relevant clinical question.