Psychiatric Dispatches

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Primary Psychiatry. 2009;16(6):12-14

FDA Approves Lamotrigine Orally Disintegrating Tablets for Bipolar I Disorder

The United States Food and Drug Administration approved lamotrigine orally disintegrating tables (Lamictal ODT, GlaxoSmithKline) for the treatment of bipolar I disorder in patients >18 years of age. Unlike previous versions of lamotrigine, lamotrigine ODT disintegrates on the tongue, thus making it easier for patients who have difficulty swallowing medication. The recommended daily dose of lamotrigine ODT is 25–200 mg/day.

The most common side effects found in clinical trails were dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, tremor, rash, fever, abdominal pain, back pain, tiredness, and dry mouth. It is also noted that patients that have an allergic reaction to lamotrigine should not take lamotrigine or lamotrigine ODT.

For more information, please see the medication’s full prescribing information at –CDN

FDA Approves Risperidone Long-acting Injection for Maintenance Treatment of Bipolar I Disorder

The US FDA approved risperidone long-acting injection (Risperdal Consta, Johnson & Johnson) for both monotherapy and adjunctive therapy to lithium or valproate in the maintenance treatment of bipolar I disorder. The medication is administered in 25, 37.5, and 50 mg doses bi-weekly.

Approval was based on two prospective, randomized, double-blind, placebo-controlled studies for the long-term treatment of bipolar I disorder. In the first study, risperidone long-acting injection as monotherapy was significantly better than placebo at delaying the time to relapse of any mood episode. In the second study, the addition of risperidone long-acting injection to a regimen of  lithium or valproate significantly delayed the time to relapse compared to current treatments plus placebo.

The most common side effects observed in all clinical trials in patients with bipolar disorder were weight increase (5% in monotherapy) and tremor and parkinsonism (>10% in adjunctive therapy trial).

For more information on risperidone long-acting injection, please visit –DC

FDA Approves Iloperidone for the Treatment of Schizophrenia

The US FDA approved iloperidone (Fanapt, Vanda) for the treatment of schizophrenia in adults. The recommended dosage range is 12–24 mg/day.

Approval was based on two short-term, placebo-controlled clinical trials of 1,310 patients meeting Diagnostic and Statistical Manual of Mental Disorders, Third and Fourth Editions criteria for schizophrenia. In the first trial, which was 4 weeks in duration, iloperidone was found to be more effective than placebo and an active control medication using the Positive and Negative Syndrome Scale. In the second trial, which was 6 weeks in duration, both the 12-mg and the 24-mg dosage of iloperidone were found to be more effective than placebo and an active control on the Brief Psychiatric Rating Scale total score.

The most common side effects reported during the clinical trials were dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, drowsiness, tachycardia, and weight increase.

For more information on iloperidone, please visit –CDN

Relationship Between Depression, Cardiovascular Disease, and HealthCare Costs in Female Patients 

A study conducted by William Whang, MD, at Columbia University, and colleagues showed that individuals diagnosed with clinical depression are also at a higher risk for cardiovascular-related deaths. Because women are twice as likely to be diagnosed with depression they are at an even greater risk for cardiovascular disease.

Whang and colleagues reinforced the importance of women being aware of this finding so that they are better able to equip themselves for the risks involved. While previous studies have focused on the correlation between depression and coronary heart disease, there was no definite evaluation of the link.

“When we looked separately at the worst symptoms and antidepressant use, there was a specific association between antidepressant use and sudden cardiac death,” Dr. Whang said. “This may well be the result of antidepressant use identifying those women with particularly severe depression, but we think it is worth studying further.”

In the study, 63,469 women who did not have heart disease at baseline were evaluated by the Nurses’ Health Study. Using the Mental Health Index, depressive symptoms were examined and found to be strongly linked to fatal heart disease moments. While there was heavy correlation between women who used antidepressants and sudden cardiac death, there was no causation for it.

“When we looked at a proxy variable for clinical depression consisting of the worst symptoms or use of antidepressants, there was an association with both sudden cardiac death fatality from coronary heart disease [CHD] that remained even with adjustment for multiple CHD risk factors,” said Dr. Whang. “The biggest implication is that management of CHD risk factors may be especially important among women with depressive symptoms.”

Although there are links between antidepressants and cardiovascular fatalities, Whang did not think that the medication should be stopped because of these statistics. Instead, he focused on how women also have an increase in fatalities associated with depression, due to the risk of fatal ventricular arrhythmias.

One of the limiting factors within the study was that researchers were not able to measure patient adherence to antidepressant method. Another limitation was that the study was an observational one, compared to a randomized controlled trial. Because of this type of study, it is impossible for the results to prove causality.

In addition to the correlation between depression and cardiovascular disease in women, high costs for treatment also prove a relationship. A study conducted by the Women’s Ischemia Syndrome Evaluation (WISE), showed that within women who are thought to have coronary artery disease, those who also suffer from depression are more likely to be obligated to higher health costs.

Three different methods were used to assess depression in women in a study that included 868 women who were simultaneously undergoing evaluations for possible heart disorders. The three techniques utilized were a history of treatment for depressive symptoms, the use of antidepressants, and the Beck Depression Inventory. Lead author Thomas Rutledge, PhD, of Veterans Affairs San Diego Healthcare System was surprised that the results consistently showed the same results.

“Whether symptoms on a questionnaire or those being treated for a depressive disorder, depression was associated with higher costs,” he said.

Depression was associated with 15% to 50% increases in cardiovascular costs over the past 5 years. One of the most significant reasons for the correlation is that women who suffer from depressive symptoms also had more cardiovascular disease events.

In addition, the relationship between depression and costs was prominent with women who did not show signs for extreme coronary artery disease. This indicated that depression may cost more for women who do not have traditional markers of heart disease. Depression seemed to be as or more important to cost prediction than most of the major chronic diseases he and his colleagues measured.

“The results of this study imply that efforts to reduce depression could translate into not only higher quality lives for women, but also potentially reduced hospital costs,” said Dr. Rutledge. “Because depression is so common in women with or at risk for heart disease, the potential cost savings could be substantial.”

The study was limited in that it did not incorporate men into the data. Therefore, the results cannot be constructed into more generalized terms. The study is particularly focused on the effects on women because women are twice as likely than men to be diagnosed with depression.

In addition, women who participated in the WISE study were symptomatic, or had suspicion of heart disease, even though 40% proved to have heart disease. The results correlate more to women who are thought to be symptomatic for heart disease and “not necessarily to those with known or more advanced heart disease.”

Funding for the WISE study was provided by the Edythe Broad Endowment for Women’s Heart Research, the Gustavus and Louis Pfeiffer Research Foundation, the Ladies Hospital Aid Society of Western Pennsylvania, the National Center for Research Resources, the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the Women’s Guild of Cedars-Sinai Medical Center. (J Am Coll Cardiol. 2009;53:950-958; J Am Coll Cardiol. 2009;53:176-183). –AC

The Presence of Sleep Disturbance in Suicidality

Many studies report on the links between chronic sleep disturbance and comorbid mood disorders, which consequently suggests a link between sleep problems and suicidality. However, most such studies are conducted in special clinical populations and their results are not well applicable to the general population.

Marcin Wojnar, MD, PhD, at the University of Michigan, and colleagues studied potential links between sleep disturbance and suicide in the United States general population. Using data from the National Comorbidity Survey Replication, they studied the relationships between suicide (thoughts, plans, and attempts) and three measures of sleep: difficulty initiating sleep, difficulty maintaining sleep, and early morning awaking.

After controlling for demographics; chronic health conditions; and mood, anxiety, and substance use disorders, they found that any of the three sleep problems assessed were significantly correlated with each measure of suicidality, including suicidal ideation (OR=2.1), planning (OR=2.6), and attempt (OR=2.5). Specifically, early morning awaking was most strongly associated with suicidal behaviors, including suicidal ideation (OR=2.0), planning (OR=2.1), and suicide attempt (OR=2.7). Difficulty initiating sleep was predictive of suicidal ideation (OR=1.9) and planning (OR=2.2). Difficulty maintaining sleep predicted suicidal ideation (OR=2.0) and suicide attempts (OR=3.0).

There is no clear consensus on how sleep disturbances lead to suicidal behaviors; however, some suggestions have considered sleep deprivation’s negative effect on cognitive function. Sleep deprivation may also cause dysfunction in the serotonin system, which is known as a significant mediator of mood and sleep functioning.

Funding for this research was provided by the United States Department of Veterans Affairs, the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse. (J Psychatr Res. 2009;43(5):526-531.) –LS

Binge Drinking Behavior May Be Detrimental to Brain Structure in Adolescents

According to the National Institute on Drug Abuse, a majority of high school seniors have consumed alcohol in their lifetime. It is estimated that >50% have reported consuming alcohol to the point of drunkenness in the past 2 weeks. A smaller percentage of students have also reported in prior studies consuming ≥5 drinks in a row (often criteria for heavy episodic or “binge” drinking) in the past 2 weeks.

Recently, researchers have sought to better understand the effects of such drinking behavior on the adolescent brain as studies have shown that the integrity of brain white matter in adult alcoholics is often compromised. However, researchers have yet to determine when effects on the brain occur in the course of exposure to alcohol.

Susan F. Tapert, PhD, of the Veterans Affairs San Diego Healthcare System and the University of California, San Diego School of Medicine, and colleagues, studied the microstructural brain white matter integrity among 28 adolescents with a history of binge drinking behavior, but who did not meet criteria for an alcohol use disorder. Tapert and colleagues hypothesized that as the adolescent brain is still developing, periods of high alcohol intake may be detrimental to the development or structure of white matter.

All study participants were 16–19 years of age and did not have a history of alcohol or drug use disorder. Binge drinking was defined as the consumption of ≥4 (for female participants) or ≥5 (for male participants) alcoholic beverages at one time 3 months prior to study beginning. Fourteen participants met criteria for binge drinking behavior. Controls and participants who reported binge drinking were matched on age, gender, and education level variables. Brain white matter integrity was measured using diffusion tensor imaging, which examined fractional anisotropy, a measure of directional coherence of white matter tracts. Comprised of neuronal axons that transport electrical signals between neurons, white matter has been shown to further develop in adolescence.

They found that adolescent participants who engaged in binge drinking behavior has reduced fractional anisotrophy than control participants in 18 brain regions, including the corpus callosum and commissural, limbic, brainstem, and cortical projection fibers, among other areas. Participants who engaged in binge drinking also had no areas of increased fractional anisotrophy than controls.

Tapert and colleagues concluded that such reduced white matter fiber coherence in those who had consumed alcohol in excess may contribute to increased lifetime hangover symptoms and a higher risk of increased lifetime alcohol consumption, as reduced coherence in six of the 18 brain regions had previously been linked to these outcomes. They added that due to these findings, alcohol use during youth in infrequent periods of excess may be responsible for compromising white matter coherence in widespread brain regions. Future longitudinal studies examining the effects of such drinking behavior on adolescents are recommended to further explain these findings.

Funding for this research was provided by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. (Alcohol Clin Exp Res. In press.) –CP

Psychiatric dispatches is written by Dena Croog, Amanda Cuomo, Christopher Naccari, Carlos Perkins, Jr., and Lonnie Stoltzfoos.