Holly A. Swartz

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence.

OBJECTIVE The prevalence of suicide attempts (SA) in bipolar II disorder (BPII), particularly in comparison to the prevalence in bipolar I disorder (BPI), is an understudied and controversial issue with mixed results. To date, there has been no comprehensive review of the published prevalence data for attempted suicide in BPII. METHODS We conducted a literature review and meta-analysis of published reports that specified the proportion of individuals with BPII in their presentation of SA data. Systematic searching yielded 24 reports providing rates of SA in BPII and 21 reports including rates of SA in both BPI and BPII. We estimated the prevalence of SA in BPII by combining data across reports of similar designs. To compare rates of SA in BPII and BPI, we calculated a pooled odds ratio (OR) and 95% confidence interval (CI) with random-effect meta-analytic techniques with retrospective data from 15 reports that detailed rates of SA in both BPI and BPII. RESULTS Among the 24 reports with any BPII data, 32.4% (356/1099) of individuals retrospectively reported a lifetime history of SA, 19.8% (93/469) prospectively reported attempted suicide, and 20.5% (55/268) of index attempters were diagnosed with BPII. In 15 retrospective studies suitable for meta-analysis, the prevalence of attempted suicide in BPII and BPI was not significantly different: 32.4% and 36.3%, respectively (OR = 1.21, 95% CI: 0.98-1.48, p = 0.07). CONCLUSION The contribution of BPII to suicidal behavior is considerable. Our findings suggest that there is no significant effect of bipolar subtype on rate of SA. Our findings are particularly alarming in concert with other evidence, including (i) the well-documented predictive role of SA for completed suicide and (ii) the evidence suggesting that individuals with BPII use significantly more violent and lethal methods than do individuals with BPI. To reduce suicide-related morbidity and mortality, routine clinical care for BPII must include ongoing risk assessment and interventions targeted at risk factors.

Brief Interpersonal Psychotherapy for Depressed Mothers Whose Children Are Receiving Psychiatric Treatment

OBJECTIVE Depressed mothers of children with psychiatric illness struggle with both their own psychiatric disorder and the demands of caring for ill children. When maternal depression remains untreated, mothers suffer, and psychiatric illness in their offspring is less likely to improve. This randomized, controlled trial compared the interpersonal psychotherapy for depressed mothers (IPT-MOMS), a nine-session intervention based on standard interpersonal psychotherapy, to treatment as usual for depressed mothers with psychiatrically ill offspring. METHOD Forty-seven mothers meeting DSM-IV criteria for major depression were recruited from a pediatric mental health clinic where their school-age children were receiving psychiatric treatment and randomly assigned to IPT-MOMS (N=26) or treatment as usual (N=21). Mother-child pairs were assessed at three time points: baseline, 3-month follow-up, and 9-month follow-up. Child treatment was not determined by the study. RESULTS Compared to subjects assigned to treatment as usual, subjects assigned to IPT-MOMS showed significantly lower levels of depression symptoms, as measured by the Hamilton Depression Rating Scale, and higher levels of functioning, as measured by the Global Assessment of Functioning, at 3-month and 9-month follow-ups. Compared to the offspring of mothers receiving treatment as usual, the offspring of mothers assigned to IPT-MOMS showed significantly lower levels of depression as measured by the Childrens Depressive Inventory at the 9-month follow-up. CONCLUSIONS Assignment to IPT-MOMS was associated with reduced levels of maternal symptoms and improved functioning at the 3- and 9-month follow-ups compared to treatment as usual. Maternal improvement preceded improvement in offspring, suggesting that maternal changes may mediate child outcomes.

The Role of Interpersonal and Social Rhythm Therapy in Improving Occupational Functioning in Patients With Bipolar I Disorder

OBJECTIVE Recent studies demonstrate the poor psychosocial outcomes associated with bipolar disorder. Occupational functioning, a key indicator of psychosocial disability, is often severely affected by the disorder. The authors describe the effect of acute treatment with interpersonal and social rhythm therapy on occupational functioning over a period of approximately 2.5 years. METHOD Patients with bipolar I disorder were randomly assigned to receive either acute and maintenance interpersonal and social rhythm therapy, acute and maintenance intensive clinical management, acute interpersonal and social rhythm therapy and maintenance intensive clinical management, or acute intensive clinical management and maintenance interpersonal and social rhythm therapy, all with appropriate pharmacotherapy. Occupational functioning was measured with the UCLA Social Attainment Scale at baseline, at the end of acute treatment, and after 1 and 2 years of maintenance treatment. RESULTS The main effect of treatment did not reach conventional levels of statistical significance; however, the authors observed a significant time by initial treatment interaction. Participants initially assigned to interpersonal and social rhythm therapy showed more rapid improvement in occupational functioning than those initially assigned to intensive clinical management, primarily accounted for by greater improvement in occupational functioning during the acute treatment phase. At the end of 2 years of maintenance treatment, there were no differences between the treatment groups. A gender effect was also observed, with women who initially received interpersonal and social rhythm therapy showing more marked and rapid improvement. There was no effect of maintenance treatment assignment on occupational functioning outcomes. CONCLUSIONS In this study, interpersonal and social rhythm therapy, with its emphasis on amelioration of interpersonal and role functioning, improved occupational functioning significantly more rapidly than did a psychoeducational and supportive approach with no such emphasis on functional capacities.

Are adults with bipolar disorder active? Objectively measured physical activity and sedentary behavior using accelerometry

BACKGROUND Little is known about physical activity and sedentary behavior of adults with bipolar disorder (BP). Physical activity and sedentary behaviors may be modifiable factors associated with elevated rates of obesity, diabetes, cardiovascular disease, metabolic syndrome, and mortality in adults with BP. METHODS Sixty adult outpatients treated for BP (> 18 yr) wore accelerometers for seven consecutive days. Each minute epoch was assigned an activity level based on the number of counts per minute; sedentary(<100 counts), light(101-1951 counts), or moderate/vigorous(>1952 counts). Adults with BP were matched 1:1 to users and non-users of mental health services (MHS) (NHANES 2003-2004) by gender, closest BMI, and age. RESULTS On average, adults with BP wore actigraphs over 17 h/day. The majority of monitoring time (78%) was classified as sedentary (approximately 13.5h/day). Light physical activity accounted for 21% of the monitoring time/day (215 min/day). None achieved 150 min/wk of moderate/vigorous activity as recommended by national guidelines. Adults with BP were significantly less active and more sedentary than MHS users and non-users in NHANES 2003-2004 (p<0.01). LIMITATIONS Majority of the participants were relatively asymptomatic with most (87%) having no more than mild depressive symptoms and none experiencing severe manic symptoms. The sedating effects of medications on physical activity were not investigated. CONCLUSION From clinical perspectives, these findings justify physical activity interventions targeting adults with BP as a possible means to improve their physical and mental health and to reduce the elevated risk of commonly observed medical comorbidities in this high-risk population.

Feasibility of Providing Culturally Relevant, Brief Interpersonal Psychotherapy for Antenatal Depression in an Obstetrics Clinic: A Pilot Study.

Objective: To minimize barriers to care, ameliorate antenatal depression, and prevent postpartum depression, we conducted a pilot study to assess the feasibility of providing brief interpersonal psychotherapy (IPT-B) to depressed, pregnant patients on low incomes in an obstetrics and gynecological (OB/GYN) clinic. Method: Twelve pregnant, depressed women were recruited as a convenience sample from the clinic and were offered a pretreatment engagement interview and eight sessions of IPT-B, followed by monthly maintenance IPT sessions up to 6-months postpartum. Results: Nine of these 12 patients (75%) completed eight sessions of IPT-B. Paired t tests showed that completers of IPT-B displayed significant improvement at posttreatment and 6-months postpartum on three measures of depression, a measure of anxiety, and some aspects of social functioning. Conclusions: These preliminary results suggest that providing depression screening and treatment to this sample in an OB/GYN clinic was feasible and accompanied by high rates of clinical and functional improvement.

Psychotherapy as monotherapy for the treatment of bipolar II depression: a proof of concept study.

OBJECTIVES We conducted a proof of concept study to determine the feasibility of using an individual psychotherapy, Interpersonal and Social Rhythm Therapy (IPSRT), as monotherapy for the acute treatment of bipolar II depression. METHODS Unmedicated individuals (n = 17) meeting DSM-IV criteria for bipolar II disorder and currently depressed received weekly psychotherapy (IPSRT) for 12 weeks. After 12 weeks of acute treatment, individuals received an additional 8 weeks of follow-up treatment consisting of continued weekly IPSRT with supplementary lamotrogine for IPSRT non-responders. RESULTS By week 12, 41% (n = 7) of the sample responded to IPSRT monotherapy (defined as > or =50% reduction in depression scores without an increase in mania scores), 41% (n = 7) dropped out of or were removed from the study, and 18% (n = 3) did not respond to treatment. By week 20, 53% (n = 9) had achieved a response and 29% (n = 5) achieved a full remission of symptoms. CONCLUSIONS Interpersonal and Social Rhythm Therapy appears to be a promising intervention for a subset of individuals with bipolar II depression. A randomized controlled trial is needed to systematically evaluate the efficacy of IPSRT as an acute monotherapy for bipolar II depression.

Pharmacotherapy for the Treatment of Acute Bipolar II Depression: Current Evidence

OBJECTIVE Bipolar II disorder is a common, recurrent, and disabling psychiatric illness, and yet little is known about how best to treat it. The pressing clinical need for evidence-based approaches to the treatment of bipolar II disorder, coupled with recent publication of pertinent studies, calls for an updated review of this literature. This review focuses on a critical examination of the evidence supporting the efficacy of treatments for acute depressive episodes in bipolar II disorder. DATA SOURCES A MEDLINE (via Ovid) search of journals, covering the period from January 1950 to January 2009, was performed to identify relevant studies. Keywords used were bipolar II disorder, bipolar disorder, bipolar depression, and pharmacotherapy. Studies were further limited to those that were in adult samples, published in peer-reviewed journals, and written in English. STUDY SELECTION We examined all randomized trials evaluating the use of pharmacotherapy in the treatment of acute bipolar II depression. Studies with mixed samples of bipolar I and II or bipolar II and unipolar depression were examined as well. Twenty-one randomized trials were identified and reviewed. DATA EXTRACTION Therapeutic agents were rated according to the quality of evidence supporting their efficacy as treatments for bipolar II depression. DATA SYNTHESIS Ninety percent of relevant trials were published after 2005. Quetiapine was judged as having compelling evidence supporting its efficacy. Lithium, antidepressants, and pramipexole were judged as having preliminary support for efficacy. Lamotrigine was considered to have mixed support. CONCLUSIONS Although progress has been made, further research on bipolar II depression is warranted.

A randomized pilot study of psychotherapy and quetiapine for the acute treatment of bipolar II depression

OBJECTIVES The differential roles of psychotherapy and pharmacotherapy in the management of bipolar (BP) II depression are unknown. As a first step toward exploring this issue, we conducted a pilot study to evaluate the feasibility and acceptability of comparing a BP-specific psychotherapy [Interpersonal and Social Rhythm Therapy (IPSRT)] to quetiapine as treatments for BP-II depression. METHODS Unmedicated individuals (n = 25) meeting DSM-IV criteria for BP-II disorder, currently depressed, were randomly assigned to weekly sessions of IPSRT (n = 14) or quetiapine (n = 11), flexibly dosed from 25-300 mg. Participants were assessed with weekly measures of mood and followed for 12 weeks. Treatment preference was queried prior to randomization. RESULTS Using mixed effects models, both groups showed significant declines in the 25-item Hamilton Rating Scale for Depression [F(1,21) = 44, p < 0.0001] and Young Mania Rating Scale [F(1,21) = 20, p = 0.0002] scores over time but no group-by-time interactions. Dropout rates were 21% (n = 3) and 27% (n = 3) in the IPSRT and quetiapine groups, respectively. Overall response rates (defined as ≥ 50% reduction in depression scores without an increase in mania scores) were 29% (n = 4) in the IPSRT group and 27% (n = 3) in the quetiapine group. Measures of treatment satisfaction were high in both groups. Treatment preference was not associated with outcomes. CONCLUSIONS Outcomes in participants with BP-II depression assigned to IPSRT monotherapy or quetiapine did not differ over 12 weeks in this small study. Follow-up trials should examine characteristics that predict differential response to psychotherapy and pharmacotherapy.

Enhancing Interpersonal Psychotherapy for Mothers and Expectant Mothers on Low Incomes: Adaptations and Additions

Intervening with depressed women during their childbearing years, especially with those on low incomes, is critically important. Not only do mothers and expectant mothers suffer unnecessarily, but their untreated depression has critical negative consequences for their families. Despite this, these women have proven especially difficult to engage in psychotherapy. In this paper we describe several adaptations and additions we have made to a brief form of Interpersonal Psychotherapy (IPT) to meet the needs of mothers and expectant mothers living on low incomes in the community who suffer from depression, but face significant practical, psychological, and cultural barriers to engaging in and staying in treatment. In addition, we present some preliminary data on the extent to which our enhanced, brief IPT approach promotes improvements in treatment engagement and retention relative to usual care for expectant mothers on low incomes.