FDA Approves Aripiprazole for Acute Treatment of Manic and Mixed Episodes in Pediatric Patients

The United States Food and Drug Administration approved aripiprazole (Abilify, Bristol-Myers Squibb, Otsuka America Pharmaceuticals) for the acute treatment of manic and mixed episodes affiliated with bipolar I disorder with or without psychotic characteristics in adolescents between 10–17 years of age.

Approval was based on results from a double-blind, placebo controlled study involving 296 pediatric bipolar patients enrolled at 54 US centers and evaluated over a 4-week period using the Young-Mania Rating Scale (Y-MRS) total score. Aripiprazole was initially administered at 2 mg/day. Patients who scored ≥20 on the Y-MRS were randomly assigned to aripiprazole doses of either 10 mg/day (n=98) or 30 mg/day (n=99). By week 4, both aripiprazole doses exhibited statistically significant improvement (P<.001) in bipolar symptoms when compared to placebo as measured by the mean change in the Y-MRS Total Score from baseline to week 4.

The most common adverse reactions to treatment were somnolence, extrapyramidal disorder, fatigue, nausea, akithisia, blurred vision, salivary hypersecretion, slight weight gain (ie, ≥7% change from baseline), and dizziness. The efficacy of aripiprazole for the maintenance treatment of bipolar I disorder in pediatric patients was not evaluated.

The recommended oral aripiprazole dose for the pediatric bipolar population 10–17 years of age is 10 mg/day.

For more information, please consult the medication’s full prescribing information (www.abilify.com). –ML


FDA Approves Fluvoxamine Extended Release for Treatment of SAD and OCD in Adults

The United States Food and Drug Administration approved once daily fluvoxamine maleate (Luvox CR, Jazz Pharmaceuticals) extended-release (ER) capsules for the treatment of social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD) in adults. Fluvoxamine in the form of immediate-release tablets was previously approved in late 2007 for the treatment of obsessions and compulsions in patients with OCD.

Effectiveness for fluvoxamine ER capsules for the treatment of SAD and OCD was demonstrated in three 12-week, multicenter, placebo-controlled studies of adult outpatients. In each study, patients were titrated in 50 mg increments over the first 6 weeks on the basis of response and tolerance from a dose of 100 mg/day to that of 100–300 mg once daily. In the two SAD studies and one OCD study, the capsules demonstrated statistically significant superiority over placebo at the 12-week primary endpoint as assessed by the Liebowitz Social Anxiety Scale total score and Yale-Brown Obsessive Compulsive Scale, respectively.

Fluvoxamine ER capsules will be available in 100 mg and 150 mg dose strengths. The most common adverse reactions were nausea, somnolence, asthenia, diarrhea, anorexia, tremor, and sweating.

For more information, please consult the medication’s full prescribing information. (www.JazzPharmaceuticals.com.) –DC


Activity Rhythms May Serve as Bipolar Disorder Indicators in Various Illness States

Patients with bipolar disorder often exhibit physiologic or behavioral symptoms such as increased or decreased activity or amount of sleep, in addition to the manic symptoms like euphoric mood and depressive symptoms that occur during the course of the disorder. However, as most of these physiologic indicators are present only during acute illness, their use during other phases of the disorder or when a patient experiences positive treatment response is limited. In addition, a state-independent physiologic indicator would allow clinicians to anticipate possible mood changes in patients throughout different phases of the disorder. 

Paola Salvatore, MD, of the Schizophrenia and Bipolar Disorder Program and International Consortium for Bipolar Disorder Research at the McLean Division of Massachusetts General Hospital in Belmont, and colleagues, investigated activity rhythms among 36 patients with bipolar disorder in acute states as well as clinical recovery and rhythms among 32 participants without bipolar disorder. Typically, activity rhythms are highly abnormal in patients with bipolar disorder. Salvatore and colleagues hypothesized that such abnormalities may persist in other bipolar states, making activity rhythms a state-independent indicator of bipolar disorder.

The authors evaluated patients with bipolar disorder during acute mania or mixed states as well as during full and sustained clinical recovery, and healthy participants using wrist-worn piezoelectric actigraphic monitoring for 72 hours. Piezoelectric actigraphic monitoring measured changes in motility levels and circadian activity rhythms during the 24-hour day and night cycle.

Salvatore and colleagues found that there were significant differences in motility patterns between patients with bipolar disorder in acute phases and healthy participants. Patients with bipolar disorder showed a lower total proportion of activity in the daytime, decreased amplitude of circadian activity, increased amounts of daytime sleeping, and an earlier peak of daily motor activity rhythm (acrophase) as compared to health participants. Patients in sustained recovery also differed from those in acute phases of bipolar disorder.

Recovered patients showed lower daily activity average, increased motility amplitude, higher percentage of nocturnal sleep, and reduced amounts of daytime sleep when compared to patients with acute illness. When compared to healthy participants, euthymic bipolar disorder patients showed 8% less daytime activity, 18% more total sleep with 11% more nocturnal sleep, and an acrophase >1 hour earlier. Results from euthymic patients remained consistent when researchers controlled for ratings of mania as measured by the Young Mania Rating Scale, depression as measured by the Hamilton Rating Scale for Depression, subjective distress, as well as the type and dosage of psychotropic medication currently being taken.

The authors concluded that the presence of an earlier acrophase for bipolar disorder patients in acute illness and those experiencing treatment response may demonstrate a stable psychobiologic trait of bipolar disorder that can act as an indicator of illness in various states. The authors added that if such an indicator is verified, it may be useful in supporting clinical diagnosis. (Bipolar Disord. 2008;10(2):256-265.) —CP


Mild Cognitive Impairment Disrupts Everyday Life and Relationships

Memory loss, contrary to common belief, is not a normal part of the aging process. A study by Rosemary Blieszner, PhD, of Virginia Polytechnic Institute and State University, and colleagues, suggests that memory loss associated with mild cognitive impairment (MCI) interferes with the everyday lives of family members and their relationships with individuals suffering from MCI.

The 3-year study consists of three parts. The first part involved two interviews with 99 economically diverse, 3-member families. The member experiencing MCI was ≥60 years of age; the second member was a non-professional caretaker (eg, spouse); and the third was a non-professional, secondary care partner such as an adult child, friend, or sibling. The first round of interviews identified three types of responses from people with MCI (ie, acceptance and desire to manage their condition, uncertainty and lack of recognition of memory changes, and denial and rejection of their condition) while the second interview analyzed how families coped with the affected individual’s condition. With the addition of 40 ethnically and racially diverse families, the second phase of the study focused on how family members dealt with the transition from MCI to Alzheimer’s disease in the affected member. The third part, which is currently underway, continues to follow and interview the families. Results thus far have found that the family members of elders with MCI had to alter their daily activities and responsibilities, contributing to distress that affects the relationships between them. This reflects patients and families’ need for ongoing information and support targeted to the patient’s particular level of incapacity and symptoms.

“[Families and patients with MCI] do not find information and support groups for Alzheimer’s disease and other dementias to be relevant or useful,” Dr. Blieszner said. “Many do not have good information about what changes are occurring in the brain and do not understand the sources of the problems they are experiencing.”

That the findings are not based on a national sample is a significant limitation, as they are from three memory clinics located in one state. However, the availability of data from the patient and two other family members in addition to interviews repeated three times over 3 years provide multi-perspective results about changes over time that are otherwise not available for MCI.

Funding for this research was provided by the Alzheimer’s Association. (Family Relations. 2007;56(2):196-209.) –ML


Depression Improvement and Five Secondary Outcomes

According to a recent study, patients receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression may see a shorter time to alleviation of depressive symptoms than for some secondary symptoms of depression, such as hopelessness or lingering somatic symptoms.The study tracked the improvement of secondary deficits associated with depression and then compared those outcomes with the outcome of the actual depressive symptoms.

James E. Aikens, PhD, at the University of Michigan in Ann Arbor, and colleagues, noted that secondary outcomes tend to worsen after depression onset and improve with its remission. Secondary outcomes have been assumed to not only depend upon improvement in depressive symptoms, but to also follow identical trajectories of change. Accordingly, Aikens and colleagues tested this convention based on two alternative hypotheses: first, that secondary outcomes could respond independently of depressive symptoms, or secondly, that secondary outcomes could respond somewhat independently of depressive symptoms.

The data for this study are from A Randomized Trial Investigating SSRI Treatment (ARTIST). The purpose of ARTIST was to evaluate clinical response to SSRIs in a primary care environment with as little research interference as possible. The two most significant ways in which ARTIST study protocol differed from primary care were randomization to one of three initial SSRIs and participation in telephone-based outcome reports during follow up.

The main outcome measure for depressive symptoms was the Symptom Checklist–20 (SCL-20). Each of the remaining five secondary outcomes—positive well-being, social functioning, hopefulness, physical symptoms, and work functioning—were assessed with separate, individual scales.

Seventy-nine percent of the baseline study population (n=573) were women (mean age=46.2 years) and 73% had a diagnosis of major depressive disorder (MDD). An average of 191 patients were randomized to one SSRI group each, including paroxetine (189), fluoxetine (193), and sertraline (191) groups. At study outset, 74% of patients met criteria for MDD, which decreased to 26% of patients by month 9. The mean SCL-20 symptom severity measure decreased as well from 1.66 to 0.78. There was no significant difference between the three SSRIs. Positive well being, one of the five secondary outcomes, and depressive symptoms followed a nearly identical outcome trajectory, improving along the same timeline.

The most significant finding, according to the authors, was that improvement in somatic complaints plateaued earlier than improvement in depressive symptoms. That is, improvement in overall somatic complaints occurred mainly during the first month of therapy, whereas depressive symptoms continued to improve through month 9 (1.2±1.0). Moderate effects were also noted in social functioning (0.9±1.1), work functioning (0.6±0.8), hopefulness (0.7±1.0), and somatic complaints (0.6±1.1).

According to Dr. Aikens, such rapid leveling of the improvement in somatic complaints was rather unexpected.

“I think we have suspected for quite some time that hopelessness cognitions may respond slower to treatment than mood symptoms,” he said. “But to see medical complaints reduce so sharply, especially at a time when initial medication side effects would be peaking—that was surprising.”

Hopelessness is sometimes associated with suicidality, but Dr. Aikens cautions that “the linkage between [the] results and suicidality can only be inferred indirectly” because the trial was not designed to assess suicidal ideation or related constructs. Instead, it was suggested that the results of this trial could guide clinicians when monitoring depressive patients who exhibit pronounced traits of hopelessness or physical pain. In addition, future investigations may determine why the improvement of somatic complaints and depressive symptoms diverge soon after treatment onset.

Funding for this research was provided by Eli Lilly. (Gen Hosp Psychiatry. 2008;30(1):26–31.) –LS


Increased Risk for Postpartum Depression in Low-income and African-American Women

Postpartum depression (PPD) is prevalent in approximately 10% to 20% of women in the United States. Studies by Lisa Segre, PhD, of the University of Iowa, and colleagues, suggest that women of low income are at a higher risk of experiencing PPD than their more affluent counterparts and African-American women are more likely to suffer from PPD than both Latino and white women.

The first study focused on the income, education, marital status, number of children, and occupational prestige of 4,332 women who gave birth 4.6 months prior to the research evaluation. They completed sociodemographic interviews and the Inventory to Diagnose Depression, which is a scale used to identify a major depressive episode according to standards in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–Text Revision. Data revealed that 40% of the women who were suffering from PPD had a low household income of <$20,000. These results indicate that social status is a significant predictor of PPD, with income as the strongest predictor.

The second study examined race and ethnicity as a factor for PPD. The Iowa Barriers to Prenatal Care Project Survey asked 26,877 English-speaking women with newborns whether they felt excessively miserable over the 2 weeks after they gave birth. Data from the survey revealed that 15.7% of the women exhibited a single depressive item, with African-American women as the most likely candidates to report a depressive mood compared to white women. Hispanic women were least likely to report a depressive mood compared to both African-American and white women.

Both studies emphasize the need for early PPD identification programs and strong social support for women with newborns. (Social Psychiatry and Psychiatric Epidemiology. 2007;42(4):316-321; Journal of Reproductive and Infant Psychology. 2006;24(2):99-106.) –ML

Dispatches is written by Dena Croog, Michelisa Lanche, Carlos Perkins, Jr., and Lonnie Stoltzfoos.