Vivien K. Burt

Course of Psychiatric Disorders across the Menstrual Cycle

&NA; Women of reproductive age with psychiatric disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest an exacerbation of symptoms during the premenstrual and menstrual phases. The usefulness of such reports is limited, however, by the lack of prospective assessments and the small number of patients involved. Additionally, many reports do not specify whether the exacerbations reflect an intensification of the underlying psychiatric disorder or a new onset of symptoms that occur only during certain phases of the menstrual cycle. Because symptomatic intensification has been reported for illnesses including schizophrenia, bipolar disorder, depression, anxiety disorders, bulimia nervosa, and substance abuse, the data bring attention to the importance of assessing the relationship between a female patients symptomatic exacerbation and the menstrual‐cycle phase in which it occurs. We present a review of the literature on the course of psychiatric symptoms across the menstrual cycle and discuss the potential effects of estrogen and progesterone on these symptoms.

Bipolar II Postpartum Depression: Detection, Diagnosis, and Treatment

Research on postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis and has largely ignored or neglected bipolar II disorder. Hypomanic symptoms are common after delivery but frequently unrecognized. DSM-IV does not consider early postpartum hypomania as a significant diagnostic feature. Although postpartum hypomania may not cause marked impairment in social or occupational functioning, it is often associated with subsequent, often disabling depression. Preliminary evidence suggests that bipolar II depression arising in the postpartum period is often misdiagnosed as unipolar major depressive disorder. The consequences of the misdiagnosis can be particularly serious because of delayed initiation of appropriate treatment and the inappropriate prescription of antidepressants. Moreover, no pharmacological or psychotherapeutic studies of bipolar postpartum depression are available to guide clinical decision making. Also lacking are screening instruments designed specifically for use before or after delivery in women with suspected bipolar depression. It is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of nonpuerperal bipolar II depression, using medications that are compatible with lactation.

Depressive Symptoms in the Perimenopause: Prevalence, Assessment, and Guidelines for Treatment

&NA; This review describes the biological changes occurring in perimenopause and analyzes epidemiological studies that shed light on the relationship between perimenopause and mood. The role of estrogen as a treatment for depressive symptoms is also examined. We found that a positive association may exist between depressive symptoms and the perimenopause, and that a prior history of depression may be associated with such symptoms. In most of the studies reviewed, the use of estrogen in replacement doses appears to improve depressive symptoms in perimenopausal patients who do not have major depression. We suggest an approach to the treatment of middle‐aged women presenting with such symptoms. No careful study of the incidence of DSM‐IV major depression associated with perimenopause has been done, and the efficacy of estrogen as a primary or adjunctive treatment for the disorder during perimenopause is unclear.

Male fertility: psychiatric considerations.

OBJECTIVE To examine: 1) current knowledge on normal biologic variation of seminal parameters; 2) how stress and psychological factors affect sperm quality in fertile and infertile males; and 3) how mental illness and psychopharmacologic agents can affect male fertility. DESIGN English-language Medline, Embase, and Psycinfo were searched for relevant publications (from 1970 to January 2011) for systematic review. SETTING None. PATIENT(S) None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Possible effects of stress, mood, and psychotropic medications on male factor fertility. RESULT(S) Male-factor infertility is influenced by myriad factors (obesity, tobacco, etc.). Stress alone may reduce testosterone levels and spermatogenesis. Infertility assessment and treatment can lead to distress and negatively affect sperm samples. Available research has failed to control for potentially confounding variables. CONCLUSION(S) Although some trends have been identified, larger-scale studies that adequately control all confounding variables are needed before conclusions can be made about the relationship between stress, psychotropic agents, and male infertility.

Bipolar Disorder and Pregnancy: Maintaining Psychiatric Stability in the Real World of Obstetric and Psychiatric Complications

This article describes complex, real-life issues faced by a woman with bipolar I disorder who wished to bear a healthy child while remaining psychiatrically well. The therapeutic issues include balancing treatment decisions that affect fetal and maternal risks. The authors address the importance of carefully considering the patient’s history of response to medications when evaluating risks to maternal and fetal health. They discuss the role of the psychiatrist as a part of the treatment team faced with unpredictable but not unexpected complexities, such as miscarriage, abnormal or questionable prenatal screening tests, gestational diabetes, and the emergence of fetal decelerations, preterm labor, and psychiatric decompensation. The article presents and evaluates treatment decisions made in the setting of multiple obstetric and psychiatric complications that do not clearly fit published algorithms. The importance of incorporating family and social supports as an integral part of the treatment plan is emphasized.

Neurobehavioral impact of menopause on mood

The menopausal transition is a time of risk for mood change ranging from distress to minor depression to major depressive disorder in a vulnerable subpopulation of women in the menopausal transition. Somatic symptoms have been implicated as a risk factor for mood problems, although these mood problems have also been shown to occur independently of somatic symptoms. Mood problems have been found to increase in those with a history of mood continuum disorders, but can also occur de novo as a consequence of the transition. Stress has been implicated in the etiology and the exacerbation of these mood problems. Estrogen and add-back testosterone have both been shown to positively affect mood and well-being. In most cases, the period of vulnerability to mood problems subsides when the woman’s hormonal levels stabilize and she enters full menopause.

Nefazodone for the treatment of postpartum depression

Antidepressant treatment studies for postpartum depression are limited to four for the SSRI’s (Appleby et al., 1997; Stowe et al., 1995; Suri et al., 2001; Misri et al., 2004), one for venlafaxine (Cohen et al., 2001) and one for bupropion (Nonacs et al., 2005). Women who suffer from postpartum depression often experience considerable anxiety (Hendrick et al., 2000). Cohen et al. (2001) suggest that reducing anxiety associated with postpartum depression may ‘‘catalyze’’ the response to antidepressant treatment. Nefazodone, a 5-HT receptor antagonist and reuptake blocker, has been shown to be effective in the treatment of depression with significant anxiety (Taylor and Prather, 2003) and may be beneficial in this unique population. We describe an eight week, open label trial of nefazodone for four women with postpartum depression and comorbid anxiety symptoms. This trial was conducted at the University of California at Los Angeles Neuropsychiatric Institute and was reviewed and approved by the institutional review board (IRB). Written informed consent was obtained in a manner approved by the IRB for subjects who participated. Inclusion criteria included outpatients between 18 and 45 years of age with a SCID confirmed diagnosis of depression in the first eight postpartum weeks, a score of 12 on the Edinburgh Postnatal Depression Scale, and a score of 14 on the Hamilton Anxiety Rating Scale. Due to the lack of data regarding the safety of nefazodone in nursing infants and a case report of drowsiness in a preterm breastfed infant (Yapp et al., 2000), breast feeding women were excluded from the study. Subjects began nefazodone treatment, 50 mg BID, and were followed weekly with clinical interviews and administration of the Ham-A and Ham-D by a blind rater. Nefazodone was titrated up to a maximum dose of 500 mg=day, as tolerated, over the first two study weeks. On entry, the mean Hamilton Anxiety (Ham-A) and Hamilton Depression (Ham-D) Rating Scale scores were 17.0 4.1 and 18.3 3.2, respectively. The mean final dose of nefazodone was 400 81.7 mg=day. One patient discontinued the study after week 4 due to lethargy (at a dose of 300 mg=day). All three remaining subjects showed improvement each week and obtained remission of anxiety (Ham-A scores of 3, 0, and 1) and depression (Ham-D scores of 3, 3, and 0) by the fifth week of the study. This remission persisted through week 8, the study endpoint. Our findings add to the limited literature on postpartum depression and suggest that nefazodone may be effective for women with postpartum depression accompanied by anxiety. Future larger double-blind, placebo-controlled studies are needed to determine if nefazodone is an effective treatment for this unique population. This study was funded in part by an unrestricted educational grant from Bristol-Myers Squibb.

The Assessment and Treatment of Postpartum Psychiatric Disorders

The authors discuss the importance of early identification and treatment of postpartum disorders. They then review the assessment, clinical characteristics, and psychotherapeutic and psychopharmacologic treatment of four major types of postpartum psychiatric conditions: postpartum blues, postpartum

DSM-V: modifying the postpartum-onset specifier to include hypomania

By failing to include it under the rubric of the postpartum-onset specifier, Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR has ignored the clinical reality that childbirth is a potent trigger of hypomania. Given the serious and occasionally tragic consequences of misdiagnosis of bipolar II depression as unipolar depression in the postpartum period, it is argued that DSM-V should consider modifying the postpartum-onset specifier to include episodes of hypomania.

Reproductive Psychiatry: The Gap Between Clinical Need and Education

Over the past three decades, there have been substantial advances in our understanding of the strong influence of sex hormones on women’s mental and physical health. In particular, the literature clearly documents that fluctuating levels of reproductive hormones can manifest as premenstrual, perinatal, andperimenopausalpsychiatricdisorders inwomenwho arevulnerable to thesefluctuations (1–3).Theresearchover the past three decades came in response to a 1985 Public Health Service task force report onwomen’s health that noted deficits in our knowledge regarding key women’s health problems and that called for an expansion of biomedical and behavioral research to emphasize conditions unique to, or more prevalent in, women (4). In response, the National Institutes of Health (NIH) created a policy encouraging inclusion of women in clinical research. Because implementation of this policy was inconsistent and unmonitored, Congress passed legislation in 1993 mandating fair inclusion of women and minorities in clinical research.As a result, in 1994NIHbeganmandating that all grant applications either include women or justify the exclusion.This policywasupdated in 2001,with furtherguidance on reporting data by sex. Research resulting from these changes has dramatically expanded knowledge of the psychiatric sequelae of reproductive cycle transitions. Due to the accumulation of ample evidence, premenstrual dysphoric disorder, described in the medical literature since the time of Hippocrates, was finally included in DSM-5 (5). Perimenopause has also been recognized as a time of heightened risk for depressive and anxiety symptoms (6–10), and the role of hormonal and other novel interventions is being investigated(11). Importantly, depression has been found to be among the most prevalent perinatal illnesses, affecting up to 15% of women in the perinatal period (12–14). As of 2003, antidepressants were being used in approximately 13% of pregnancies—a rate that had climbed dramatically in the previous 10 years (15, 16); with the current U.S.birthrate, thatmeans thatmore than600,000fetusesevery year are exposed to depression and/or its treatments. The risks of untreated antenatal depression have been identified and include a lower likelihood of engaging in prenatal care; increased rates of smoking and alcohol use; poorer physical health; and higher rates of preeclampsia, gestational diabetes, preterm birth, and low birth weight (17, 18). Epigenetic effects of antenatal stress and depression on fetal development (“fetal programming”) are increasingly understood (19–21), as are the adverse long-term effects of postpartum depression on children (22–25). In addition to these risks, there is also considerable literature on the potential risks of treatments to both mother and fetus (26–28), as well as a body of literature concerning drug disposition and pharmacokinetic changes in pregnancy and postpartum that may require dosage adjustments (29–32). Clinicians who specialize in the field routinely use this new scientific information to craft individualized risk analyses for pregnant women who require treatment. This increased body of knowledge has led to the growth of international professional societies such as the Marcé International Society for Perinatal Mental Health and the International Society of Psychosomatic Obstetrics andGynecology. It has influenced public policy initiatives, including, for example, a number of statewide perinatal depression projects (33) and mandatory screenings (34). It has also begun to be disseminated into clinical practice via the emergence and growth of specialized clinical programs, which include outpatient and inpatient programs that offer perinatal consultations and ongoing treatment (35); perinatal care settings that integratemental health care (36); a peripartumday hospital (37); and, most recently, the first mother-baby inpatient unit in the United States (38). Such programs have been created by specialists out of necessity becausemany general psychiatrists havenot sufficientlymastered thisnewbodyofknowledgeand are unwilling or unable to treat pregnant and postpartum patients. While there is no doubt that such programs provide outstanding care (39, 40), they can neither begin to keep up with theclinical demandthat leads towaiting listsmonths long