Geetha Shivakumar

Effects of exercise and physical activity on anxiety

The beneficial effects of regular physical activity on health are indisputable in the field of modern medicine. Exercise is often the first step in lifestyle modifications for the prevention and management of chronic diseases. According to a US Department of Health and Human Services report on physical activity, regular exercise significantly reduced causes of mortality by up to 30% for men and women (DHHS, 2002). These health benefits are seen consistently across all age groups and racial/ethnic categories. The Centers for Disease Control and Prevention currently recommends 30 min of moderate- to high-intensity exercise for at least 5 days a week for all healthy individuals (DHHS, 2002). In addition to significantly lowering causes of mortality, regular exercise and physical activity lowers prevalence of chronic disease(s). There is a strong evidence to support that 2–2.5 h of moderate- to high-intensity exercise per week is sufficient to reduce one’s risk for the occurrence of a chronic disease(s). Numerous epidemiological studies have shown that exercise improves one’s self-esteem, and a sense of wellbeing. Individuals who exercise regularly exhibit slower rates of age-related memory and cognitive decline in comparison to those who are more sedentary. Such observations have provided the basis for using exercise to improve memory and cognition in cognitive disorders such as Alzheimer’s Dementia. Adults who engage in regular physical activity experience fewer depressive and anxiety symptoms, thus supporting the notion that exercise offers a protective effect against the development of mental disorders (van Minnen et al., 2010). Anxiety disorders are common psychiatric conditions with a lifetime prevalence of nearly 29% in the United States (Kessler et al., 2005). These disorders are chronic, debilitating, and impact multiple aspects of one’s life. The economic burden of anxiety disorders in the US was estimated to be

Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety☆

42.3 billion in the 1990s (Greenberg et al., 1999). The prominent anxiety disorders defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) are General Anxiety Disorder (GAD), Panic Disorder (PD), Posttraumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), Social Anxiety Disorder, and Specific Phobia (APA, 2000). The exact etiology and pathophysiology of these conditions is not fully understood. Comprehending the effects of exercise and physical activity on the mechanisms of anxiety disorders might further our knowledge of these psychiatric disorders. The purpose of this article is to highlight the known and emerging mechanisms that may result in the anxiolytic effects of exercise.

A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression

BACKGROUND The treatment of bipolar disorder is often complicated by the presence of a co-occuring anxiety disorder. Although second generation antipsychotics are being used with increasing frequency in bipolar patients, their anxiolytic effects have not been well studied in this population. METHODS The anxiolytic effect of risperidone 0.5-4 mg/day was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 111 patients with bipolar disorder and a co-occuring panic disorder or generalized anxiety disorder (GAD). The primary outcome measure was the Clinician Global Improvement-21 Anxiety scale (CGI-21 Anxiety). Secondary measures included the Hamilton Anxiety Scale (HAM-A) and the Sheehan Panic Disorder Scale. RESULTS On the last-observation-carried forward analysis of repeated measures analysis of variance (ANOVA), risperidone was not more effective than placebo for the CGI-21 Anxiety score or the other anxiety outcome measures. Risperidone was well tolerated, with only two patients withdrawing because of adverse events. LIMITATIONS The risperidone treated group had more patients with mixed states and lifetime panic disorder at randomization than the placebo group. The study was limited to 8 weeks and to individuals with bipolar and comorbid panic disorder or GAD. The results may not be applicable to risperidone as an add-on treatment to mood stabilizers, or to bipolar disorder comorbid with anxiety disorders other than panic disorder or GAD. CONCLUSIONS Risperidone monotherapy was not an effective anxiolytic for bipolar patients with comorbid panic disorder or GAD in doses of 0.5-4 mg/day over 8 weeks of treatment. The efficacy of other second generation antipsychotics and mood stabilizers on anxiety in patients with bipolar disorder and a co-occuring anxiety disorder should be investigated in double-blind, placebo-controlled studies.

Are bipolar mood symptoms affected by the phase of the menstrual cycle

BACKGROUND Treatment studies are lacking for patients with bipolar II disorder (BDII). The objective of this study was to compare lamotrigine (LTG) and lithium (Li) monotherapy for the treatment of BDII depression. METHODS Patients with BDII acute depression were randomized to open-label monotherapy with LTG or Li, and evaluated by trained raters blinded to treatment. Patients were titrated to 200 mg/day of LTG over 8 weeks or at least 900 mg/day of Li over 2 weeks (serum level 0.6-1.2 mEq/L), and seen biweekly for 16 weeks. The primary outcome variable was change in the Hamilton Depression Rating Scale 17-item (Ham-D(17)), evaluated using mixed effects random regression. RESULTS Both groups showed significant improvement from baseline to endpoint on the Ham-D(17) (p<0.0001), with no between group differences (p=0.95). Seventy-two percent of the population was rapid cycling by DSM-IV criteria. No differences in response were noted between rapid cyclers and non-rapid cyclers. Early termination for any cause was 42%. The Li group reported significantly more side effects, although drop-out due to side effects did not differ between groups. LIMITATIONS This study was limited by an open treatment design, a lack of placebo arm, and uneven treatment groups. CONCLUSIONS Lamotrigine and lithium were effective monotherapy for BDII depression, with comparable response and remission rates. Naturalistic design and lack of placebo limit conclusions, though patient history indicated long standing depression unlikely to be alleviated by time. Patients who received Li reported more side effects, but this did not appear to impact drop-out rates.

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

BACKGROUND Evidence suggests gender differences may exist in bipolar disorder, and a review of the literature shows that more women than men may experience rapid-cycling bipolar disorder. The issues contributing to these gender differences are unknown; a number of case reports have indicated the possibility of mood changes secondary to hormonal influences during the menstrual cycle. We sought to examine the relationship between bipolar disorder and menstrual cycle-related mood changes. To our knowledge, this is one of the largest samples in the literature addressing this issue. METHODS Outpatient women with bipolar disorder I, bipolar disorder II, and not otherwise specified (NOS), between the ages of 18 and 45, were evaluated. The National Institute of Mental Health Life Chart Method-p (NIMH-LCM-p) was used for daily mood ratings of depression and mania. Repeated measures of ANOVA and t tests were conducted separately for depressive and for manic symptom scores. RESULTS One hundred nineteen women met the age criterion, and only 41 women met the rest of the inclusion criteria. In this sample of 41 women, there was no significant relationship between phases of the menstrual cycle (early and late follicular and early and late luteal phases) and changes in depression or mania. In an exploratory examination, 8 of 41 women showed a numerically higher mean depression score in the luteal phase than in the follicular phase; 5 of 41 women showed a numerically higher mean mania score in the luteal phase than in the follicular phase of the menstrual cycle. CONCLUSIONS Different phases of the menstrual cycle were unrelated to depression and mania in a heterogeneous group of women with bipolar disorder. Prospective studies are needed to identify a vulnerable subpopulation in a homogeneous clinical sample.

Serotonin reuptake inhibitor use in pregnancy and the neonatal behavioral syndrome

OBJECTIVES To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation. METHODS Participants included 55 adults (age 18-65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1-3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25). RESULTS Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO. CONCLUSIONS While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.

Ethical Issues in Perinatal Mental Health Research

Objective. To assess the severity of neonatal behavioral syndrome (NBS) in infants of serotonin reuptake inhibitor (SRI)-treated pregnancies, compared with infants of women with psychiatric illness not treated with medication. Methods. This was a retrospective cohort study of pregnancies followed in a prenatal clinic for women with psychiatric illness. Infants of women who received SRI medication through delivery (SRI-treated) were compared with those who did not receive treatment or discontinued medication before the last month of pregnancy (SRI-untreated). NBS was defined as one or more of the following: jitteriness, irritability, lethargy, hypotonia, hypertonia, hyperreflexia, apnea, respiratory distress, vomiting, poor feeding, or hypoglycemia. Results. Findings of NBS were identified in 28% of 46 SRI-treated pregnancies and 17% of 59 untreated pregnancies. There were no differences in rates of prematurity (4% vs. 7%), fetal growth restriction (6% vs. 2%), transfer to a higher nursery for NBS (11% vs. 10%), respiratory abnormality (7% vs. 5%), or hospitalization duration among infants with NBS findings (2 vs. 6 days). Conclusions. Findings of NBS were identified in 28% of SRI-exposed neonates. However, these infants were not more likely than unexposed infants to be admitted to a higher nursery, experience respiratory abnormalities, or have prolonged hospitalization.

Managing Posttraumatic Stress Disorder and Major Depression in Women Veterans During the Perinatal Period

Purpose of review To review the background of current ethical standards for the conduct of perinatal mental health research and describe the ethical challenges in this research domain. Recent findings Current literature reflects a growing sentiment in the scientific community that having no information regarding the impact of psychiatric treatment on the mother and developing fetus/infant poses dangers that may exceed the risks involved in research. However, without sufficient consensus across the scientific community, both regulatory bodies and perinatal researchers find themselves without a framework for decision making that satisfactorily limits the risks and facilitates the benefits of participation of pregnant and lactating women in clinical research. Summary Psychiatric research in perinatal mental health is critically important as it enables clinicians and patients to participate in informed decision-making concerning treatment for psychiatric disorders. Specific areas of concern include fetal safety, maternal risk, the therapeutic misconception, commercial interests, forensic/legal issues, the informed consent process, and study design. Developing guidelines that address ethical challenges and include the views and concerns of multiple stakeholders could improve the access of perinatal women to the benefits of participation in mental health research in addition to providing evidence-based mental healthcare for this subpopulation.

Ethical challenges in designing, conducting, and reporting research to improve the mental health of pregnant women: The voices of investigators and IRB members

The recent surge in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) era women Veterans, most of whom are younger compared to other women Veterans, presenting with mental health issues is expected to pose new clinical challenges. Treatment of mental health conditions in women Veterans is not considered comprehensive without adequate examination of the impact of reproductive events across the life span, such as their menstrual cycle, pregnancy and postpartum period, and menopausal transition. The overarching aim of this article is to discuss emerging clinical issues in managing common psychiatric conditions such as posttraumatic stress disorder and major depression during pregnancy and postpartum period in the VA healthcare system and secondly, to identify steps to advance the knowledge and understanding of these complex issues. Information to be gained in this area has immediate clinical application in the overall management of major psychiatric conditions in women Veterans during pregnancy and postpartum, and implications for policy-making decisions.

Progression of Major Depression during Pregnancy and Postpartum: A Preliminary Study

Background: Legitimate concern for fetal safety often precludes women who are pregnant or planning to become pregnant from participating in randomized controlled trials (RCTs), preventing the development of an empirically-derived evidence base for the safety and efficacy of treatments. Perinatal science can only move forward when the research community understands and addresses the practical and ethical roadblocks impeding this research. Methods: To understand these challenges better, our study team interviewed 15 perinatal mental health investigators from 12 leading academic institutions in the United States and 6 members of the respective institutional review boards (IRBs). Results: Respondents confirmed seven broad ethical challenges. Through analyzing interview transcripts, we identified four themes: research design/methodology, safety, participant selection/recruitment, and autonomy. Fifteen subthemes further delineate the complexities of the issues revealed in narratives describing specific experiences related to these themes. Conclusions: The lack of reasonable solutions to these ethical challenges is a barrier to rigorous clinical research in this population, preventing the collection of empirical evidence for psychiatric care in the perinatal setting. Our study population confirms that the current federal human subjects protections guidelines (i.e., 45 CFR 46 Subpart B) do not fully address the themes of concern that emerged in the interviews. There is a need for greater flexibility in accepting womens competence to balance the risks and benefits of research participation for themselves and their fetuses.