Crystal T. Clark

Ketamine for treatment-resistant unipolar depression: current evidence.

Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action andsignificant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD.

Lamotrigine Dosing for Pregnant Patients With Bipolar Disorder

OBJECTIVE Little information is available on the need for dosage changes for lamotrigine in pregnant women with bipolar disorder. The authors present new data on serial serum levels of lamotrigine in pregnant patients on lamotrigine monotherapy. They also review the epilepsy literature on use of lamotrigine during pregnancy. METHOD Lamotrigine serum samples were obtained from eight mother-infant pairs at different time points during pregnancy and the postpartum period. RESULTS All of the women were taking lamotrigine throughout pregnancy. Serum-level-to-dose ratios were lower during pregnancy than the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg. Three patients had an increase of 50 mg to their daily dose across pregnancy. The change in serum lamotrigine levels in the postpartum period ranged from a 30% decrease to a 640% increase compared with the first level obtained during pregnancy. Level-to-dose ratios obtained within 4 weeks after delivery reflected a mean level 402% greater than the baseline level during gestation. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels. CONCLUSIONS The pattern of lamotrigine changes during pregnancy in these women with bipolar disorder was consistent with that described in the epilepsy literature.

Does Screening with the MDQ and EPDS Improve Identification of Bipolar Disorder in an Obstetrical Sample

Women with bipolar disorder (BD) are at high risk for postpartum affective episodes and psychosis. Although validated screening tools are available for postpartum unipolar depression, few screening tools for hypomania/mania exist. Screening tools for BD in the postpartum period are essential for improving detection and planning appropriate treatment. We evaluated whether adding the Mood Disorders Questionnaire (MDQ) to the Edinburgh Postnatal Depression Scale (EPDS) increased the identification of BD in the early postpartum period.

Factors associated with onset timing, symptoms, and severity of depression identified in the postpartum period

BACKGROUND Unipolar and bipolar depression identified in the postpartum period have a heterogeneous etiology. The objectives of this study are to examine the risk factors that distinguish the timing of onset for unipolar and bipolar depression and the associations between depression onset by diagnosis, and general and atypical depressive symptoms. METHODS Symptoms of depression were assessed at 4- to 6-weeks postpartum by the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms in an obstetrical sample of 727 women. Data were analyzed using ANOVA, Chi-square, and linear regression. RESULTS Mothers with postpartum onset of depression were more likely to be older, Caucasian, educated, married/cohabitating, have one or no previous child, and have private insurance in contrast to mothers with pre-pregnancy and prenatal onset of depression. Mothers with bipolar depression were more likely to have a pre-pregnancy onset. Three general and two atypical depressive symptoms distinguished pre-pregnancy, during pregnancy, and postpartum depression onset, and the presence of agitation distinguished between unipolar and bipolar depression. LIMITATIONS The sample was urban, which may not be generalizable to other populations. The study was cross-sectional, which excludes potential late onset of depression (after 4-6 weeks) in the first postpartum year. CONCLUSIONS A collective set of factors predicted the onset of depression identified in the postpartum for mothers distinguished by episodes of unipolar versus bipolar depression, which can inform clinical interventions. Future research on the onset of major depressive episodes could inform prophylactic and early psychiatric interventions.

Double Duty: Does Epidural Labor Analgesia Reduce Both Pain and Postpartum Depression?

Nearly one-third of pregnant women in the United States undergo cesarean delivery.1 Effective analgesia is crucial to maximize the mother’s comfort, increase her mobility, and support lactation and emotional attachment to her newborn. The incidence of severe acute postpartum pain is approximately 11%.2 Chronic pain incidence varies by study and ranges from 1% to 4% to 10% after vaginal delivery and 6% to 18% after cesarean delivery.3,4 Chronic pain frequently co-occurs with depression. Eisenach et al.2 evaluated whether mode of delivery or acute postpartum pain was associated with persistent pain and depression 8 weeks after childbirth in a multicenter, prospective, longitudinal cohort study (n = 1288). The prevalence of severe acute pain within 36 hours of birth was 10.9%. Women with severe acute pain had a 2.5-fold increased risk of persistent pain and a 3-fold increased risk for postpartum depression compared with those with mild postpartum pain.

Placentophagy: therapeutic miracle or myth?

Postpartum women are consuming their placentas encapsulated, cooked, and raw for the prevention of postpartum depression (PPD), pain relief, and other health benefits. Placentophagy is supported by health advocates who assert that the placenta retains hormones and nutrients that are beneficial to the mother. A computerized search was conducted using PubMed, Medline Ovid, and PsychINFO between January 1950 and January 2014. Keywords included placentophagy, placentophagia, maternal placentophagia, maternal placentophagy, human placentophagia, and human placentophagy. A total of 49 articles were identified. Empirical studies of human or animal consumption of human placentas were included. Editorial commentaries were excluded. Animal placentophagy studies were chosen based on their relevance to human practice. Ten articles (four human, six animal) were selected for inclusion. A minority of women in developed countries perceive placentophagy to reduce PPD risk and enhance recovery. Experimental animal research in support of pain reduction has not been applied in humans. Studies investigating placenta consumption for facilitating uterine contraction, resumption of normal cyclic estrogen cycle, and milk production are inconclusive. The health benefits and risks of placentophagy require further investigation of the retained contents of raw, cooked, and encapsulated placenta and its effects on the postpartum woman.

Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study

BACKGROUND Women with bipolar disorder are at high risk for relapse/recurrence postpartum. Among all mood stabilizers, lithium has the largest evidence base for efficacy in the peripartum period, but lamotrigine is increasingly prescribed for bipolar spectrum disorders during pregnancy. The aim of this study was to investigate whether lamotrigine use during pregnancy is as effective as lithium in the prevention of severe episodes postpartum. METHODS Danish national registries were used to identify pregnancies of women with a diagnosis of bipolar spectrum disorders at the time of conception who used lamotrigine or lithium during pregnancy. We compared the risk of inpatient psychiatric admission within three months postpartum between women who used lamotrigine (N=55) versus lithium (N=59) during pregnancy. A logistic regression model was used to calculate crude and adjusted odds ratios. RESULTS We did not find a significant difference in the risk of postpartum psychiatric admission between women who used lamotrigine versus lithium during pregnancy (7.3% versus 15.3% respectively, adjusted OR 0.83; 95% CI 0.22-3.14). We adjusted for year of delivery, parity, previous admissions and antidepressant/benzodiazepine use during pregnancy. Other variables did not differ substantially between groups. LIMITATIONS We used an observational design and therefore patients were not randomized to lamotrigine or lithium. The study has a small sample size. CONCLUSIONS Lamotrigine was not inferior to lithium in the prevention of severe postpartum episodes. Our findings suggest lamotrigine could be a reasonable alternative treatment option for bipolar disorder during pregnancy in patients with vulnerability for depression and may prevent severe episodes postpartum.

Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study

We conducted a prospective naturalistic study of pregnant women with bipolar disorder (BD) to evaluate symptoms of BD across childbearing and assess whether pharmacotherapy reduced their severity.

Bipolar disorder and psychotropic medication: Impact on pregnancy and neonatal outcomes

OBJECTIVE The hypotheses were: (1) pregnant women with bipolar disorder (BD) have less favorable pregnancy outcomes than unaffected women, and (2) psychotropic treated women with BD have better outcomes than un-medicated women. METHOD This prospective study included 174 mother-infant dyads. Women had BD without psychotropic exposure (BD-NP, n = 38), BD with psychotropic treatment (BD-P, n = 49), or neither psychotropic exposure nor major mood disorder (Comp, n = 87). Maternal characteristics were completed at 20 weeks gestation and evaluated for associations with delivery and birth outcomes. We performed multiple regressions on infant outcomes with adjustment for maternal age, race, employment status, use of illicit drugs and pre-pregnancy BMI. RESULTS The BP-P, BP-NP and Comp groups varied significantly on sociodemographic characteristics. Women with BD were more likely to be less educated, unemployed, single, and use tobacco and illicit drugs than women in the Comp group. Compared to women with BD-NP, women with BD-P were more likely to be older and educated. Approximately 10% of all infants were delivered preterm. No significant differences in outcome occurred for APGAR scores < 8, NICU admissions, sex or infant length. Infants of mothers with BD-NP had significantly smaller head circumferences (HC) than the other groups, adjustment for confounding variables mitigated this association. CONCLUSIONS The overall pregnancy outcomes for women with BD were similar to those in the Comp group. The reduced HC in women with untreated BD appears due to factors related to disadvantaged sociodemographic status, a higher proportion of female births, and/or a protective effect of medication in the BD-P group.

Treatment of Peripartum Bipolar Disorder

Bipolar disorder affects women throughout their childbearing years. During the perinatal period, women with bipolar disorder are vulnerable to depressive episode recurrences and have an increased risk for postpartum psychosis. Perinatal screening is critical to identify women at risk. Although medications are the mainstay of treatment, the choice of pharmacotherapy must be made by the patient based on a risk-benefit discussion with her physician. For optimal dosing in pregnancy, therapeutic drug monitoring may be required to maintain effective drug concentrations. Residual symptoms of bipolar depression are treatable with bright light therapy as an alternative to medication augmentation.