Delayed sleep timing and circadian rhythms in pregnancy and transdiagnostic symptoms associated with postpartum depression.

Later sleep timing, circadian preference, and circadian rhythm timing predict worse outcomes across multiple domains, including mood disorders, substance use, impulse control, and cognitive function. Disturbed sleep is common among pregnant and postpartum women. We examined whether sleep timing during third trimester of pregnancy predicted postpartum symptoms of mania, depression, and obsessive-compulsive disorder (OCD). Fifty-one women with a previous, but not active, episode of unipolar or bipolar depression had symptoms evaluated and sleep recorded with wrist actigraphy at 33 weeks of gestation and 2, 6, and 16 weeks postpartum. Circadian phase was measured in a subset of women using salivary dim light melatonin onset (DLMO). We divided the sample into "early sleep" and "late sleep" groups using average sleep onset time at 33 weeks of gestation, defined by the median-split time of 11:27 p.m. The "late sleep" group reported significantly more manic and depressive symptoms at postpartum week 2. Longer phase angle between DLMO and sleep onset at 33 weeks was associated with more manic symptoms at postpartum week 2 and more obsessive-compulsive symptoms at week 6. Delayed sleep timing in this sample of at-risk women was associated with more symptoms of mania, depression, and OCD in the postpartum period. Sleep timing may be a modifiable risk factor for postpartum depression.

Infant sleep and feeding patterns are associated with maternal sleep, stress, and depressed mood in women with a history of major depressive disorder (MDD).

Our goal was to examine associations of infant sleep and feeding patterns with maternal sleep and mood among women at risk for postpartum depression. Participants were 30 women (age ± SD = 28.3 ± 5.1 years) with a history of MDD (but not in a mood episode at enrollment) who completed daily sleep diaries, wore wrist actigraphs to estimate sleep, and had their mood assessed with the Hamilton Depression Rating Scale (HAM-D-17) during four separate weeks of the perinatal period (33 weeks pregnancy and weeks 2, 6, and 16 postpartum). They logged their infants' sleep and feeding behaviors daily and reported postnatal stress on the Childcare Stress Inventory (CSI) at week 16. Mothers' actigraphically estimated sleep showed associations with infant sleep and feeding patterns only at postpartum week 2. Shorter duration of the longest infant-sleep bout was associated with shorter maternal sleep duration (p = .02) and lower sleep efficiency (p = .04), and maternal sleep efficiency was negatively associated with the number of infant-sleep bouts (p = .008) and duration of infant feeding (p = .008). Neither infant sleep nor feeding was associated with maternal sleep at 6 or 16 weeks, but more disturbed infant sleep and more frequent feeding at 6 weeks were associated with higher HAM-D scores at 6 and 16 weeks and higher CSI scores. Sleep in the mother-infant dyad is most tightly linked in the early postpartum weeks, but mothers continue to experience disturbed sleep and infant sleep and feeding behaviors continue to be associated with mothers' depressive symptoms and stress ratings as long as 16 weeks postpartum. These data imply that interventions designed to improve maternal sleep and postpartum mood should include both mothers and infants because improving infant sleep alone is not likely to improve maternal sleep, and poor infant sleep is linked to postpartum depression and stress.

A pilot study to compare fluoxetine, calcium, and placebo in the treatment of premenstrual syndrome.

Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of premenstrual syndrome. A comparison of these agents to placebo may guide treatment selection. The goal of this pilot study was to compare fluoxetine and calcium to placebo.We enrolled 39 women with at least 3 moderate to severe premenstrual symptoms and functional impairment. The trial compared fluoxetine (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the course of 4 menstrual cycles. The Inventory of Depressive Symptomatology, Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement scales, and Daily Record of Severity of Problems were used to measure symptoms.Symptom improvement was greatest for the fluoxetine group, although significance was achieved only for the Daily Record of Severity of Problems (ß = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical Global Impression-Improvement (ß = -1.03; 95% confidence interval= -1.70 to -0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were between 0.80 and 2.08, whereas the effect sizes for calcium were only between 0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome, whereas the effect of calcium was much smaller. Results of this pilot do not support the need for a larger study that would compare these compounds.

Circadian phase shifts and mood across the perinatal period in women with a history of major depressive disorder: a preliminary communication.

BACKGROUND: Perinatal changes in maternal sleep patterns may modify circadian phase. Our objectives were to (a) measure changes in circadian phase and phase angle between salivary dim light melatonin onset (DLMO) and sleep onset across the perinatal period; and (b) prospectively examine associations between circadian measures and depressed mood in women with a history of major depressive disorder (MDD). METHODS: Twelve women (age±SD=26.9±5 years) who fulfilled DSM-IV criteria for history of MDD (but not in a mood episode at enrollment) were studied from third trimester of pregnancy through postpartum week 6. Participants completed sleep diaries, wore wrist actigraphs and light sensors, and had mood assessed with the Hamilton Depression Rating Scale (HAMD-17) during 3 separate weeks of the perinatal period; they gave saliva samples at 33 weeks gestation and 6 weeks postpartum to determine DLMO phase. RESULTS: Nine women had DLMO phase shifts ≥30 min. On average±SD, new mothers phase delayed 42±80 min (range=163 min phase delay to 144 min phase advance). The time interval between average actigraphic sleep onset and DLMO was shorter at 6 weeks postpartum compared to 3rd trimester in 9 of 12 women, indicating that most new mothers were going to bed closer to the onset of endogenous melatonin secretion. Circadian measures were associated with depressed mood at postpartum weeks 2 and 6. LIMITATIONS: These data are preliminary findings from a small sample and require replication. CONCLUSIONS: We observed individual differences in magnitude and direction of circadian phase shifts and their timing relative to sleep across the perinatal period. These measures were correlated with postpartum depressive symptoms. These preliminary data indicate that changes in perinatal circadian rhythms may contribute to the development of postpartum mood disorders.

Low-dose sertraline in the treatment of moderate-to-severe premenstrual syndrome: efficacy of 3 dosing strategies.

OBJECTIVE: Many studies have demonstrated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of premenstrual dysphoric disorder, but few studies have investigated the efficacy of SSRIs in the treatment of premenstrual syndrome (PMS). The objective of this study was to evaluate the safety and efficacy of sertraline in the treatment of moderate-to-severe PMS using 3 different dosing strategies: luteal phase (2 cycles), followed by continuous dosing throughout the month (1 cycle), followed by dosing begun at the first onset of PMS symptoms, or "symptom-onset" dosing (1 cycle). METHOD: 314 women with PMS from 22 U.S. sites were randomly assigned to fixed-dose treatment with sertraline (25 or 50 mg/day) or placebo for 4 menstrual cycles after a single-blind, placebo lead-in cycle. Assessments included the Daily Symptom Report (DSR), the Clinical Global Impressions-Severity of Illness and -Improvement scales, the Patient Global Evaluation scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, and the Social Adjustment Scale-Self Report. RESULTS: Intermittent luteal-phase dosing with low doses of sertraline (25 and 50 mg/day) produced significant improvement across 2 menstrual cycles, based on total DSR scores, compared with placebo. Continuous and symptom-onset dosing were also effective in treating PMS symptoms, particularly at the lower dose of 25 mg/day. CONCLUSIONS: The results of the current study suggest that low doses of sertraline may be a safe, effective, and well-tolerated treatment for moderate-to-severe PMS.

Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.

PURPOSE: This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of a new oral contraceptive (OC) formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mug in treating symptoms of premenstrual dysphoric disorder (PMDD). METHOD: The OC formulation or placebo was administered for 24 days in a 28-day cycle (24/4), rather than the usual 21-day active treatment, 7-day inert-pill regimen. Participants (N=64) were randomized to either study treatment for three cycles and then after a washout period of one treatment-free cycle switched to the alternate treatment. RESULTS: The mean decrease from baseline for total Daily Record of Severity of Problems (DRSP) scores while using drospirenone/EE was significantly greater than for placebo (-12.47, 95% CI=-18.28, -6.66; p<.001). A positive response (i.e., a score of 1 or 2 in the Clinical Global Impressions-Improvement scale) occurred in 61.7% and 31.8% of subjects while taking drospirenone/EE and placebo, respectively (p=.009). CONCLUSION: Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.

Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder.

OBJECTIVE: To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder. METHODS: This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 microg. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4). RESULTS: Scores on the total Daily Record of Severity of Problems decreased by -37.49 in the drospirenone/ethinyl estradiol group and by -29.99 in the placebo group (adjusted mean difference -7.5, 95% confidence interval [CI] -11.2 to -3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by -19.2 and -15.3 in active-treatment and placebo groups, respectively (adjusted mean difference -3.9, 95% CI -5.84 to -2.01; P = .003); physical symptom scores were reduced by -10.7 and -8.6 in active-treatment and placebo groups, respectively (adjusted mean difference -2.1, 95% CI -3.3 to -0.95; P < .001); and behavioral symptom scores were reduced by -7.7 and -6.2 in active-treatment and placebo groups, respectively (adjusted mean difference -1.5, 95% CI -2.251 to -0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients. CONCLUSION: A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 mug improves symptoms associated with premenstrual dysphoric disorder. LEVEL OF EVIDENCE: I.

Paroxetine Controlled Release for Premenstrual Dysphoric Disorder: Remission Analysis Following a Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To compare the efficacy and safety of paroxetine controlled release (CR) (12.5 mg/day or 25 mg/day) versus placebo in premenstrual dysphoric disorder (PMDD).Method: A double-blind, randomized, placebo-controlled trial was conducted over 3 menstrual cycles in women aged 18-45 years with confirmed DSM-IV PMDD in 47 outpatient centers across the United States and Canada from November 1999 to January 2002. The primary efficacy measure was the visual analog scale (VAS)-Mood, which is the mean of 4 core symptoms: irritability, tension, depressed mood, and affective lability.Results: A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013). Paroxetine CR was generally well tolerated.Conclusion: Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated.