Prophylactic Management of Women With Bipolar Disorder During Pregnancy and the Perinatal Period: Clinical Scenario-Based Practical Recommendations From A Group of Perinatal Psychiatry Authors.

ABSTRACT: Many women with bipolar disorder experience episodes of illness or relapses over the perinatal period, especially in the immediate postpartum period. Risks associated with treated/untreated psychopathologies and fetal exposure to bipolar medications make the management of bipolar disorder during these periods challenging for clinicians and patients. In light of the available effectiveness and reproductive safety data, the current clinical update based on the opinions of a group of international perinatal psychiatry authors recommends general considerations and specific management strategies for each possible clinical scenario, including mixed features, predominant polarity, diagnosis of subtypes of bipolar disorder, severity of previous episodes, and risk of recurrence of mood episodes.

Learning from public health practice: the development of a library of community-centered practice examples.

BACKGROUND: Valuable learning derived from public health practice can be captured through practice-based case studies, also known as practice examples. Practice examples of participatory interventions supplement the evidence base by providing information on the complexities of implementation in communities. This paper reports on a Public Health England project to build a bank of community-centered practice examples based on robust processes of collection and curation. METHODS: The multidisciplinary project had three phases: (i) development and piloting a process to collect practice examples, (ii) refining review processes and gathering further examples via national and regional teams (iii) maintenance of an accessible collection on the library platform. RESULTS: The project resulted in a searchable collection of 55 practice examples illustrating participatory approaches in public health practice. The collection shows diversity in terms of settings, population, focus and type of approach used to work with communities. A secondary outcome was the development of generic guidance and templates for further collections on public health topics. CONCLUSIONS: This project illustrates how information on the implementation of community-centered approaches in real-life contexts can be gathered and disseminated through a transferable process. Having collections of practice examples supports knowledge exchange in public health as learning is shared.

Removal of babies at birth and the moral distress of midwives.

BACKGROUND: Midwives and nurses appear vulnerable to moral distress when caring for women whose babies are removed at birth. They may experience professional dissatisfaction and their relationships with women, families and colleagues may be compromised. The impact of moral distress may manifest as anger, guilt, frustration, anxiety and a desire to give up their profession. While there has been much attention exploring the concept of moral distress in midwifery, this is the first study to explore its association in this context. AIM: This article explores midwives' experiences of moral distress when providing care to women whose babies were removed at birth and gives valuable insight into an issue nurses and midwives encounter in their profession. METHODS: Four mothers and eight midwives took part in this research. Narrative inquiry incorporating photo-elicitation techniques was used to generate data; mothers were interviewed face to face and midwives through focus groups. The images and audio data were collected, transcribed and analysed for emerging themes. For the purpose of this article, only the midwives' stories are reported. This research received a favourable ethical opinion from the University of Surrey Ethics committee. ETHICAL CONSIDERATIONS: This study received a favourable ethical approval from a higher education institutes ethics committee. RESULTS: Midwives who care for women whose babies are removed at birth report it as one of the most distressing areas of contemporary clinical practice. Furthermore, they report feelings of guilt, helplessness and betrayal of the midwife-mother relationship. Many of the midwives in this study state that these experiences stay with them for a long time, far more than more joyful aspects of their role. CONCLUSION: Midwives experience moral distress. Support systems, education and training must be available to them if we are to reduce the long-term impact upon them, alleviate their distress and prevent them from leaving the profession.

Positive screening rates for bipolar disorder in pregnant and postpartum women and associated risk factors.

OBJECTIVE: Bipolar disorder affects 2-8% of pregnant and postpartum women; untreated illness is associated with poor outcomes. This study aimed to describe bipolar disorder screening rates in obstetric settings and associated characteristics. METHOD: Women were recruited during pregnancy through three months postpartum from 14 obstetric clinics in Massachusetts. The Mood Disorder Questionnaire (MDQ) was used to screen for bipolar disorder; a subset previously diagnosed with bipolar was also examined. Differences in characteristics by screening outcome were tested using chi-square and t-tests. RESULTS: Of 574 participating women, 18.8% screened positive for bipolar disorder. Compared to those with negative, those with positive bipolar screens had 18.5-times the prevalence of positive substance use screens (11.1% vs. 0.6%, p < 0.001) and 3.4-times reported feeling they were not receiving adequate psychiatric help (24.0 vs. 7.0%, p < 0.001). Less than half of those with positive bipolar screens (42.0%) and 61.3% with pre-existing bipolar reported receiving current psychiatric care. CONCLUSIONS: Almost one in five perinatal women screened positive for bipolar disorder. Positive screenings were associated with comorbid substance use and low treatment rates. This study highlights the importance of screening for bipolar disorder during the perinatal period and the need for systematic approaches to ensure adequate assessment and follow-up. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT02760004.

Bipolar Disorder in the Menopausal Transition.

PURPOSE OF REVIEW: We review recent data on bipolar disorder in menopausal-aged women, particularly in women undergoing the menopausal transition (MT). We discuss evidence on the severity of symptoms in bipolar women during the MT. Moreover, we address two factors in bipolar disorder and menopausal research: standardized menopausal staging and women's conceptualization of their menopausal and bipolar symptoms. RECENT FINDINGS: While there are few studies within the last 5 years on bipolar women undergoing the MT, new evidence suggest that mood symptoms in women worsen with progression through the MT. Consistent use of the standardized menopausal staging system can facilitate understanding of the timing of worsening symptoms. Moreover, whether women conceptualize their symptoms as arising from their MT or bipolar disorder can influence whether they seek hormonal therapy or psychiatric treatment, respectively. The MT is a potential time for mood instability in vulnerable women, which can manifest as first-onset development of bipolar disorder or increased symptom severity in women with pre-existing bipolar disorder. Adoption of a standardized menopausal staging may offer novel frameworks for understanding of the role of the MT in bipolar disorder.

Regularity of self-reported daily dosage of mood stabilizers and antipsychotics in patients with bipolar disorder.

BACKGROUND: Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. METHODS: Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. RESULTS: There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). CONCLUSION: Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

LEARNS: A creative approach to analysing and representing narrative data incorporating photo-elicitation techniques.

BACKGROUND: Diversity exists in how storied data gathered in narrative inquiry is analysed and represented, more so when there is a need to combine multiple data collection methods, including photographs. AIM: This paper discusses the use of an analytical framework entitled LEARNS developed as part of a PhD study that has potential to fill this gap. RESULTS: The step-by-step framework presented in this paper was developed in order to analyse the data collected in this research study and gives understanding and insight into the experience of mothers whose babies are removed at birth. The LEARNS framework provides transparency and credibility; it also negates the need to restrict findings to broad themes via content/thematic analysis. CONCLUSIONS: LEARNS could offer other researchers a reliable framework to use for future social science research.

Vitamin D supplementation in bipolar depression: A double blind placebo controlled trial.

OBJECTIVE: Bipolar depression is difficult to treat. Vitamin D supplementation is well tolerated and may improve mood via its neurotransmitter synthesis regulation, nerve growth factor enhancement and antioxidant properties. Vitamin D adjunct reduces unipolar depression, but has not been tried in bipolar depression. METHODS: 18-70yos with DSM IV bipolar depression and Vitamin D deficiency (<30 ng/ml) were randomized in a controlled double blind trial of 5000IU Vitamin D3 po qday supplementation versus placebo for twelve weeks. Change in Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS), medication, and tolerance were assessed q2weeks. RESULTS: 16 VitD vs 17 placebo subjects did not differ in baseline characteristics (mean = 44 yo, SD = 13), VitD level (19.2 ± 65.8  g/ml vs 19.3 ± 5.5 ng/ml respectively) or mood ratings (MADRS 21.3 ± 6.4 vs 22.8 ± 6.9 respectively). At 12wks, the placebo group VitD levels remained unchanged, while the VitD group levels increased to 28 ng/ml. MADRS score decreased significantly in both placebo (mean = 6.42 (95% CI [2.28 to 10.56]) and VitD groups (mean = 9.54 (95% CI[3.51 to 15.56]) (p = 0.031), but there were no differences between treatment groups (time by treatment interaction estimate: 0.29, t(23) = 0.14, p = 0.89); VitD and placebo groups had similar reductions in YMRS and HAM-A. Vitamin D3 was well tolerated. CONCLUSIONS: In this small study, despite a greater rise in Vitamin D levels in the VitD supplementation group, there was no significant difference reduction in depressive symptoms. However both groups' VitD levels remained deficient. Vitamin D3 supplementation vs placebo did not improve reduction in mood elevation or anxiety symptoms.

Lifelong estradiol exposure and risk of depressive symptoms during the transition to menopause and postmenopause.

OBJECTIVE: Depression risk increases during the menopausal transition (MT) and initial postmenopausal years-both times of significant fluctuations of estrogen. Research to date provides limited support for the hypothesis that estrogen fluctuations play a role in the greater susceptibility to midlife depression. Importantly, not all women report depressive symptoms during the MT, and recent reports suggest that duration of exposure to estradiol throughout the adult years may also play a role in vulnerability to depression. This study examines patterns of estrogen exposure during the reproductive years and risk of depression during the MT and early postmenopausal years. METHODS: A longitudinal, US community-based, multiethnic study of menopause. Data were collected at baseline and annually for 10 years, and included 1,306 regularly menstruating premenopausal women, aged 42 to 52 years at study entry. The main outcome was incidence of high level of depressive symptoms, Center for Epidemiological Studies Depression Scale (CES-D) score at least 16, in the MT and initial postmenopausal years, independent of premenopausal depression symptoms. Risk factors examined were duration of estrogen exposure (menarche to MT), duration of hormonal birth control use, pregnancies, and lactation. RESULTS: In a multivariate adjusted model, longer duration of estrogen exposure from menarche to MT onset was significantly associated with a reduced risk of depression (CES-D ≥16) during the MT and 10 years or less postmenopause (odds ratio 0.85, 95% confidence interval 0.78-0.92). Longer duration of birth control use was associated with a decreased risk of CES-D at least 16 (odds ratio 0.90, 95% confidence interval 0.83-0.98), but number of pregnancies or breastfeeding was not. CONCLUSIONS: Patterns of reproductive lifetime exposure to estrogen are associated with risk of high depressive symptoms during the MT and initial postmenopausal years; longer exposure to estrogen seemed protective.

BMI calculation in older people: The effect of using direct and surrogate measures of height in a community-based setting.

BACKGROUND & AIMS: There is currently no consensus on which measure of height should be used in older people's body mass index (BMI) calculation. Most estimates of nutritional status include a measurement of body weight and height which should be reliable and accurate, however at present several different methods are used interchangeably. BMI, a key marker in malnutrition assessment, does not reflect age-related changes in height or changes in body composition such as loss of muscle mass or presence of oedema. The aim of this pilot study was to assess how the use of direct and surrogate measures of height impacts on BMI calculation in people aged ≥75 years. METHODS: A cross-sectional study of 64 free-living older people (75-96 yrs) quantified height by two direct measurements, current height (HC), and self-report (HR) and surrogate equations using knee height (HK) and ulna length (HU). BMI calculated from current height measurement (BMIC) was compared with BMI calculated using self-reported height (BMIR) and height estimated from surrogate equations for knee height (BMIK) and ulna length (BMIU). RESULTS: Median difference of BMIC-BMIR was 2.31 kg/m2. BMIK gave the closest correlation to BMIC. The percentage of study participants identified at increased risk of under-nutrition (BMI < 20 kg/m2) varied depending on which measure of height was used to calculate BMI; from 5% (BMIC), 7.8% (BMIK), 12.5% (BMIU), to 14% (BMIR) respectively. CONCLUSIONS: The results of this pilot study in a relatively healthy sample of older people suggest that interchangeable use of current and reported height in people ≥75 years can introduce substantial significant systematic error. This discrepancy could impact nutritional assessment of older people in poor health and lead to misclassification during nutritional screening if other visual and clinical clues are not taken into account. This could result in long-term clinical and cost implications if individuals who need nutrition support are not correctly identified. A consensus is required on which method should be used to quantify height in older people to improve accuracy of nutritional assessment and clinical care.

Symptom severity of bipolar disorder during the menopausal transition.

BACKGROUND: Little is known about the mood symptom experience of women with bipolar disorder during the menopausal transition (MT). Yet times of rapid hormonal decline, such as the postpartum, are associated with increased risk of severe mood episodes in bipolar disorder, and the MT is a time of increased risk for unipolar depression in women with or without a history of depression. METHODS: Enrollment included 56 women 40-60 years old diagnosed in the bipolar spectrum who were experiencing menopausal symptoms or were up to 5 years since their final menstrual period. Menopausal stages included early menopause, late menopause, or early postmenopause based on standardized criteria. Observational, prospective standardized mood symptom and reproductive hormone assessments were completed periodically. Concurrent menopausal symptoms as well as history of mood exacerbation during past reproductive events were assessed. RESULTS: Forty-four women were included in the main analysis. The average Montgomery-Asberg Depression Rating Scale (MADRS) score was 4.43 points higher in the late transition/early postmenopausal stage women (n = 29) compared to the early menopausal stage women (n = 15) (±SE 2.14; p = 0.039), corresponding to a roughly 10 % higher score (range 0-40) in the late/post stage across all study visits. Results were similar for the Young Mania Rating Scale (YMRS), where the average score was 2.54 points higher in the late/early postmenopausal stage women compared to the early menopausal stage women (±SE 1.15; p = 0.027), also roughly 10 % higher (range 0-26). Estradiol and follicle-stimulating hormone (FSH) absolute levels as well as between-visit change in levels were not notably associated with YMRS or MADRS during study observation. Total Greene Climacteric Symptom (menopausal symptom) score was significantly associated with MADRS but not YMRS. History of mood exacerbation premenstrually and/or postpartum was not significantly associated with YMRS or MADRS severity during the MT. CONCLUSIONS: These results support the theory that times of increased reproductive hormonal changes, such as the late MT and early postmenopause, here compared to early MT, are associated with greater mood symptom severity in bipolar spectrum women. Nonetheless, absolute or change in FSH and estradiol levels were not significantly associated with depression or mood elevation severity.

Common use of dietary supplements for bipolar disorder: a naturalistic, self-reported study.

BACKGROUND: Dietary supplements are taken by about half of Americans. Knowledge of dietary supplement use is important because they may interact with prescription drugs or other supplements, cause adverse reactions including psychiatric symptoms, or contain inherently toxic ingredients or contaminants. This study explores the use of dietary supplements by patients with bipolar disorder in the US. METHODS: Data were obtained from an ongoing, naturalistic study of patients with bipolar disorder who received pharmacological treatment as usual. The patients self-reported their daily mood, sleep, and medications taken, including all drugs prescribed for bipolar disorder or that the patient felt impacted their mood. These included other prescribed drugs, over-the-counter drugs and dietary supplements. Drugs that received premarketing approval from the FDA were not included as dietary supplements. Patient demographics and daily medication use were characterized. RESULTS: Data were available from 348 patients in the US who returned a mean 249.5 days of data. In addition to prescribed psychiatric drugs, 101 of the 348 patients (29 %) used a dietary supplement for at least 7 days and 69 (20 %) used a supplement long term (for at least 50 % of days). Of the 101 supplement users, 72 (71.3 %) took one supplement daily. The 101 patients tried over 40 different supplements, and the long-term users took 19 different supplements. The most commonly taken supplements for both groups were fish oil, B vitamins, melatonin, and multivitamins. Patients using supplements were more likely to be white (p < 0.001), older (p = 0.009), and ill for more years (p = 0.025). CONCLUSIONS: Many patients with bipolar disorder use dietary supplements in addition to prescribed drugs. Physicians should obtain detailed information about all dietary supplements taken by patients with bipolar disorder.

Influence of light exposure during early life on the age of onset of bipolar disorder.

BACKGROUND: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Would a student midwife run postnatal clinic make a valuable addition to midwifery education in the UK?--a systematic review.

BACKGROUND: There is growing evidence in the UK that some National Health Service improvements, particularly in the postnatal period, are having an impact on the quality and variety of student midwives' clinical experiences, making it challenging for them to meet the standards set by the regulatory body for midwives and receive a licence to practice. A possible solution to this may be the introduction of a Student Midwife integrated Learning Environment (SMiLE) focusing upon the delivery of postnatal care (PN) through a student run clinic. OBJECTIVE: To identify the current state of knowledge, regarding the educational outcomes of students who engage with student run clinics (SRC) and the satisfaction of clients who attend them. Search strategy--BNI, CINAHL, EMBASE, and MEDLINE were searched for articles published until April 2014. SELECTION CRITERIA: Studies, nationally and internationally, were carried out on healthcare students running their own clinics. Outcome measures were the evaluation of educational outcomes of students and client satisfaction were included. DATA COLLECTION AND ANALYSIS: Data were extracted, analysed and synthesised to produce a summary of knowledge, regarding the effectiveness of SRCs. MAIN RESULTS: 6 studies were selected for this review. AUTHORS' CONCLUSIONS: The findings that SRC can offer advantages in improving educational outcomes of students and provide an effective service to clients are encouraging. However, given the limited number of high-quality studies included in this review, further research is required to investigate the effectiveness of SRC.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

BACKGROUND: The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS: Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS: There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS: Recall bias for onset and family history data. CONCLUSIONS: A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Evaluation of reproductive function in women treated for bipolar disorder compared to healthy controls.

OBJECTIVES: The purpose of the present study was to investigate the reproductive function of women with bipolar disorder (BD) compared to healthy controls. METHODS: Women diagnosed with BD and healthy controls with no psychiatric history, aged 18-45 years, were recruited from a university clinic and surrounding community. Participants completed a baseline reproductive health questionnaire, serum hormone assessment, and ovulation tracking for three consecutive cycles using urine luteinizing hormone (LH)-detecting strips with a confirmatory luteal-phase serum progesterone. RESULTS: Women with BD (n = 103) did not differ from controls (n = 36) in demographics, rates of menstrual abnormalities (MAs), or number of ovulation-positive cycles. Of the women with BD, 17% reported a current MA and 39% reported a past MA. Dehydroepiandrosterone sulfate and 17-hydroxyprogesterone levels were higher in controls (p = 0.052 and 0.004, respectively), but there were no other differences in biochemical levels. Medication type, dose, or duration was not associated with MA or biochemical markers, although those currently taking an atypical antipsychotic agent indicated a greater rate of current or past MA (80% versus 55%, p = 0.013). In women with BD, 22% reported a period of amenorrhea associated with exercising or stress, versus 8% of controls (p = 0.064). Self-reported rates of bulimia and anorexia nervosa were 10% and 5%, respectively. CONCLUSIONS: Rates of MA and biochemical levels did not significantly differ between women with BD and controls. Current atypical antipsychotic agent use was associated with a higher rate of current or past MA and should be further investigated. The incidence of stress-induced amenorrhea should be further investigated in this population, as should the comorbid incidence of eating disorders.

Giving you every reason to SMiLE.

This article outlines the plans to develop a student midwife integrated learning environment (SMILE) which will focus upon the delivery of postnatal (PN) care to women and families whilst also creating an innovative clinical learning environment for students. The SMiLE PN hub (facilitated by student midwives, supervised by a qualified midwife/sign-off mentor) has been designed to fuse seamlessly with current PN provision and provide an alternative environment for women to access a wide range of PN services. This service proposal not only increases the amount of PN learning opportunities and experience of students but also provides a much needed hub of PN activity for women and their families. It provides drop-in breastfeeding support, signposting to additional support networks and scheduled daily parenting workshops, such as baby bathing and safe sleeping advice.

Drug treatment patterns in bipolar disorder: analysis of long-term self-reported data.

BACKGROUND: The objective of this study is to investigate drug treatment patterns in bipolar disorder using daily data from patients who received treatment as usual. METHODS: Patients self-reported the drugs taken daily for about 6 months. Daily drug use and drug combinations were determined for each patient, both by the specific drugs and by medication class. The drug load was calculated for all drugs taken within a medication class. RESULTS AND DISCUSSION: Four hundred fifty patients returned a total of 99,895 days of data (mean 222.0 days). The most frequently taken drugs were mood stabilizers. Of the 450 patients, 353 (78.4%) took a stable drug combination for ≥50% of days. The majority of patients were taking polypharmacy, including 75% of those with a stable combination. Only a small number of drugs were commonly taken within each medication class, but there were a large number of unique drug combinations: 52 by medication class and 231 by specific drugs. Eighty percent of patients with a stable combination were taking three or less drugs daily. Patients without a stable combination took drugs but made frequent changes. Taking more than one drug within a medication class greatly increased the drug load. To summarize, (1) patients were more likely to take a mood stabilizer than any other drug; (2) although most patients were taking polypharmacy, there were no predominant drug regimens even among those taking a stable combination; and (3) most patients with a stable combination take a relatively small number of drugs daily. The wide variation in drug regimens and numerous possible drug combinations suggest that more evidence is needed to optimize treatment of bipolar disorder.

Antidepressant dosage taken by patients with bipolar disorder: factors associated with irregularity.

BACKGROUND: This study analyzed regularity in the daily dosage of antidepressants taken by patients with bipolar disorder and identified the factors associated with irregularity. METHODS: Daily self-reported medication dosage taken and mood ratings were available from 144 patients who received treatment as usual. All 144 patients took the same antidepressant for at least 100 days. One hundred eleven of these patients were also taking a mood stabilizer. Approximate entropy (ApEn) was used to measure serial regularity in daily dosage. Regularity is the tendency that values within a time series remain the same on incremental comparisons. Drug holidays (missing three or more consecutive days) were also determined. Generalized estimating equations (GEE) were used to estimate if any demographic or clinical variables were associated with regularity. RESULTS: Although the mean percent of days missing doses was only 18.6%, there was a wide range of regularity in the daily antidepressant dosage. Drug holidays were common, occurring in 41% of the analyses. Factors significantly associated with irregularity were as follows: total number of psychotropic medications (p = 0.005), pill burden (p = 0.005), and depression (p = 0.015). Neither the percent of days missing doses nor the drug holidays were associated with any demographic or clinical factors. For patients taking both antidepressants and mood stabilizers, there was no significant difference in regularity in daily dosage between these drugs. DISCUSSION: There can be considerable irregularity in daily dosage despite a low percent of days missing doses. Medication regimen complexity and depressed mood are associated with increased irregularity. Daily regularity in drug dosage may be more dependent on the individual than on the specific drug. Research on the clinical impact of irregularity in daily dosage of antidepressants is needed.

Progression of female reproductive stages associated with bipolar illness exacerbation.

OBJECTIVES: Late perimenopause and early postmenopause confer an increased risk of depression in the population, yet bipolar disorder mood course during these times remains unclear. METHODS: Clinic visits in 519 premenopausal, 116 perimenopausal (including 13 women transitioning from perimenopause to postmenopause), and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study over 19.8 ± 15.5 months were analyzed for mood state. History of postpartum and perimenstrual mood exacerbation and current hormone therapy were evaluated as potential mood predictors. RESULTS: A progression in female reproductive stage (premenopause, perimenopause, and postmenopause) was significantly associated with percent of visits decreasing in euthymia (29.3%, 27.0%, 25.0%, respectively, p < 0.05), decreasing in syndromal mood elevation (5.3%, 4.1%, and 3.0%, respectively, p < 0.001), and increasing in subsyndromal symptoms (47.3%, 50.7%, and 52.7%, respectively, p = 0.05). Thirteen women transitioning from peri- to postmenopause had a significantly greater proportion of visits in syndromal depression (24.4%, p < 0.0005) compared to premenopausal, perimenopausal, and postmenopausal women, while depression in the latter three groups (18.1%, 18.1%, and 19.3%, respectively) did not differ. Perimenstrual and/or postpartum mood exacerbation, or hormone therapy did not significantly alter depression during perimenopause. CONCLUSIONS: A progression in female reproductive stages was associated with bipolar illness exacerbation. A small number of women transitioning from perimenopause to postmenopause had significantly greater depression than other female reproductive groups. Euthymia and mood elevation decreased with progressing female reproductive stage. Menstrual cycle or postpartum mood exacerbation, or current hormone therapy use, was not associated with perimenopausal depression. Future studies, which include hormonal assessments, are needed to confirm these preliminary findings.