Wednesday, October 7, 2015

FDA Approves Aristada for the Treatment of Schizophrenia

The Food and Drug Administration on Monday approved Aristada (aripiprazole lauroxil), a long-acting injectable antipsychotic, for the treatment of schizophrenia. The medication requires administration by a health care professional every four to six weeks.

The approval of Aristada was based, in part, on the results of a 12-week clinical trial of 623 participants with schizophrenia who were experiencing an acute exacerbation. Participants were randomly assigned to receive a gluteal intramuscular injection of aripiprazole lauroxil (441 mg), aripiprazole lauroxil (882 mg), or matching placebo once monthly for 12 weeks.

Patients in the 441 mg and 882 mg aripiprazole lauroxil groups demonstrated greater improvements in total scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Improvement scale than those treated with placebo. The most common side effects reported by participants receiving the medication were insomnia, headaches, and akathisia.

“Long-acting medications to treat schizophrenia can improve the lives of patients,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the Center for Drug Evaluation and Research at the FDA. “Having a variety of treatment options and dosage forms available for patients with mental illness is important so that a treatment plan can be tailored to meet the patient’s needs.”

Similar to other atypical antipsychotics used to treat schizophrenia, Aristada comes with a Boxed Warning alerting health care professionals about an increased risk of death associated with off-label use of the medication to treat behavioral problems in older adults with dementia-related psychosis. To date, no atypical antipsychotic has been approved to treat dementia-related psychosis.

According to a press release by Alkermes Plc, the manufacturers of Aristada, the newly approved antipsychotic is being prepared to be launched “immediately.”

For related information on aripiprazole, see the Psychiatric News article “FDA To Review Application for Abilify Pill With Ingestible Tracking Device,” featured in most recent issue of PsychoPharm.

(Image: Hurst Photo/Shutterstock)

Tuesday, October 6, 2015

Study Finds SGAs Do Not Substantively Increase Risk of Major Birth Defects

The use of second-generation antipsychotics (SGAs) during the first trimester does not appear to substantively increase the risk of major birth malformations, according to a report published today in AJP in Advance.

Given that discontinuation of medication during pregnancy can lead to relapse or worsening of illness in patients with psychiatric disorders, the results challenge the clinical practice of abruptly stopping maintenance treatment for psychiatric disorders during pregnancy, the study authors said.

Lee Cohen, M.D., of Massachusetts General Hospital along with researchers from several other institutions tracked the progress of 214 infants who were exposed to SGAs during the first trimester and a comparison group of 89 infants whose mothers had a history of psychiatric illness but who did not take SGAs during pregnancy. The women receiving SGAs were enrolled in the National Pregnancy Registry for Atypical Antipsychotics.

Three major malformations were identified among exposed infants. One infant had a transposition of the great arteries after first-trimester exposure to aripiprazole, quetiapine, bupropion, and labetalol. Another infant had a ventricular septal defect with surgical repair and had been exposed to ziprasidone, sertraline, and lamotrigine. Lastly, an imperforate hymen was identified in an infant exposed to aripiprazole, bupropion, and trihexyphenidyl. One major malformation was identified in the comparison group. The risk of major malformations reported in the exposed group was approximately two and a half times higher than in the unexposed group (6.2% versus 2.6%), although this was not statistically significant.

“Based on the 214 cases of first-trimester exposure to second-generation antipsychotics, it is reasonable to conclude that these agents as a class are not major teratogens,” the study authors wrote.

They concluded, “In summary, our results suggest that the use of a second-generation antipsychotic during the first trimester does not substantively increase the risk of major malformations. … [F]or women with substantial psychiatric morbidity and good response to a second-generation antipsychotic, maintenance treatment with a second-generation antipsychotic during pregnancy may be the most prudent treatment option, similar to recommendations for continued treatment for pregnant women with other serious and chronic medical conditions, such as epilepsy.”

AJP Editor Robert Freedman, M.D., added, “As a field, we have become aware that both psychiatric illness itself and the drugs used to treat it can adversely affect the outcome of pregnancy. Cohen and colleagues have performed a careful study of matched groups of pregnant women with mental illness—those treated with second-generation antipsychotics versus those treated with other medications. At this point, it is helpful to clinicians to know that no evidence for a particular adverse risk profile for second-generation antipsychotics has emerged.”

For related information, see the Psychiatric News article “Study Examines Association Between SSRIs, Birth Defect Risks.”

(Image: pio3/Shutterstock)

Monday, October 5, 2015

Study Suggests Stimulants Are Safe, Effective for Treating ADHD in Youth With Heart Defects

Youth with attention-deficit/hyperactivity disorder (ADHD) and congenital heart disease may be able to safely take stimulant medications for their ADHD, so long as proper care and diligence is taken, according to research presented yesterday at the Society for Developmental and Behavioral Pediatrics Annual Meeting in Las Vegas.

A team of researchers from Cincinnati Children's Hospital Medical Center compared the health outcomes of 44 youth (aged 6 to 18) with congenital heart defects who were taking stimulants and found no increased risk for death or changes in cardiac vital signs, such as blood pressure or heart rate, when compared with youth with similar heart defects who were not taking stimulants. The youth taking stimulants also showed significant improvements in their ADHD symptoms.

“Children with congenital heart disease are at high risk for ADHD, but fears about cardiovascular side effects, including sudden death, limit the use of stimulant medications,” Julia Anixt, M.D., a developmental and behavioral pediatrician at Cincinnati Children's Hospital Medical Center, said in a press release. Since 2006, the Food and Drug Administration has required warning labels on stimulant medications that caution that they generally should not be used in patients with serious heart problems due to the increased risk of serious cardiovascular complications.

“This study indicates that stimulants are both effective and safe when prescribed with appropriate monitoring and in collaboration with the patient's cardiologist,” Anixt said.

For related information, see the Psychiatric News article “Pediatricians Urged to Adhere Better to ADHD Care Practices.”


Saturday, October 3, 2015

APA President Calls for Gun Control Measures in Wake of Oregon Tragedy

In a blog post today, APA President RenĂ©e Binder, M.D., called for the implementation of “common sense measures” to reduce access to firearms in this country. Her call to action came in response to the mass shooting on Thursday that took the lives of nine people at Umpqua Community College in Roseburg, Ore., as well as that of the 26-year-old gunman. Nine other people were wounded in the attack.

“As physicians,” she wrote, “we have the opportunity to educate our patients about the risks of keeping guns in the home particularly in the presence of children, adolescents, people with dementia, people with mental illnesses, including substance use disorders, who are at risk of harming themselves or others, and people who abuse children or partners. Currently, a number of states prevent physicians from asking questions about guns. This needs to be changed.”

Among the measures that APA supports are background checks and waiting periods before gun purchases, closing gun-show loopholes, product safety regulations, safe storage requirements, and gun-free college campuses and hospitals. Also, Binder noted that temporary firearm restraining orders could be one way to protect potential victims of these tragedies—family members and/or law enforcement could go before a judge and request that guns be temporarily removed from an individual who is likely to be dangerous toward himself and/or others.

To those who want to connect gun violence with mental illness, Binder emphasized that people with mental illness are far more likely to be victims of violence and that the majority of individuals with mental illness will never be violent toward others; the risk of self-harm is far greater. “Stronger indicators of risk include a history of violent behavior, domestic violence, and drug or alcohol abuse” she noted. “We urge states to develop new procedures for the temporary removal of access to guns during periods of elevated risk.”

Echoing President Obama in his address to the nation on Thursday, Binder said, “Our hopes and prayers will not be enough to stem the tide of gun violence in our country. We need decisive action in favor of responsible gun regulation. Until then, gun violence remains a significant threat to America’s public health, and as physicians, we have a vital role in advocating for change.”

For information on the response of the Oregon Psychiatric Physicians Association to the tragedy, see yesterday’s Psychiatric News Alert.

Friday, October 2, 2015

Oregon Psychiatrists Respond to Mass Shooting Incident

America’s latest mass shooting prompted a quick response from the Oregon Psychiatric Physicians Association (OPPA) to help survivors, families, and friends affected by the tragedy yesterday.

The incident took the lives of nine people at Umpqua Community College in Roseburg, Ore., as well as that of the 26-year-old gunman. Another seven people were wounded in the attack.

Dan Bristow, M.D., a psychiatrist with Kaiser Permanente in Portland, Ore., and the public information chair of the OPPA, emphasized the need to engage the news media to help educate the public about the psychological consequences to the community.

It is too soon to understand the motivations of the gunman, said Bristow. “This is a time to support, and be supported by, the ones we love—friends, family, neighbors, and fellow Oregonians.”

The OPPA posted messages on its website urging just that and suggesting ways that adults could discuss such traumatic events with children.

Bristow said he plans to travel to Roseburg, 180 miles south of Portland, later today to provide perspective on the event to local media and coordinate a longer-term response with area psychiatrists in that underserved area of the state.

The goal, he said, was to be attuned to the needs of the community and offer OPPA’s assistance as needed.

Look for a full report on the tragedy and OPPA's response in a future issue of Psychiatric News.

(Image: Shutterstock)

Thursday, October 1, 2015

Meta-Analysis Highlights Ketamine’s Rapid, Yet Transient Antidepressant Effect

Even as the excitement over the potential of ketamine and other NMDA receptor antagonists for antidepressant treatment has grown in recent years, there have been concerns that off-label clinical use of ketamine as a therapeutic agent may be outpacing scientific scrutiny. While the authors of a meta-analysis appearing today in the American Journal of Psychiatry report that current efficacy data suggest ketamine infusion provides a rapid therapeutic benefit for patients with depression, they caution that the fleeting nature of this therapeutic benefit combined with ketamine’s potential for abuse and neurotoxicity warrants further investigation.

For the study, researchers from the APA Task Force on Novel Biomarkers and Treatments scoured the literature for placebo-controlled, double-blind, randomized clinical trials examining ketamine and other NMDA antagonists in the treatment of depression.

The analysis of seven trials (encompassing 147 ketamine-treated participants) confirmed that a single intravenous infusion of ketamine consistently produced a rapid and robust antidepressant effect that peaked within 24 hours of administration, accompanied by brief psychotomimetic and dissociative effects. However, by day 7, these antidepressant effects were largely diminished. An additional five trials examining ketamine’s ability to augment electroconvulsive therapy (ECT) (89 ketamine-treated patients) revealed that ketamine accentuated the antidepressant effects of ECT following an initial treatment but not at the conclusion of the ECT treatment regimen.

The task force also analyzed the findings of several randomized, controlled trials of other NMDA antagonists, including lanicemine, memantine, and N2O, and two partial agonists at the NMDA coagonist site, d-cycloserine and rapastinel. They found that while lanicemine, memantine, and N2O—which bind to the receptor at the same site as ketamine—failed to consistently demonstrate efficacy, d-cycloserine and rapastinel significantly reduced depressive symptoms without psychotomimetic and dissociative effects.

“The results from existing NMDA receptor antagonist studies are decidedly mixed,” said D. Jeffrey Newport, M.D., M.S., M.Div., a professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine and member of the APA Task Force on Novel Biomarkers and Treatments. “Therapeutic response to ketamine is rapid and robust but fleeting at best. … Results with other NMDA antagonists have unfortunately been largely disappointing. Nevertheless, early experience with ketamine suggests that glutamatergic strategies for treating depression warrant further investigation,” he told Psychiatric News.

“Although the antidepressant effect of ketamine appears to be clear, it’s increasingly widespread use in the community is of concern for several reasons, including the virtual absence of any data on serial administration, dosing schedules, tachyphylaxis to the therapeutic effects, and need for cardiac monitoring during administration, as well as the concerns of abuse liability and neurotoxicity,” said Charles Nemeroff, M.D., Ph.D., the Leonard M. Miller Professor and Chairman of the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine and Task Force member. Additionally, Nemeroff told Psychiatric News, “The precise mechanism of action of ketamine’s antidepressant effect remains obscure.”

Nemeroff said the Task Force is working on developing recommendations for ketamine use. “This is important because of the unusual situation in which we find ourselves, namely a drug approved for one use by the FDA has found its way into the psychiatric pharmacopoeia without the usual high standards and wealth of data in large clinical studies required for FDA approval,” he said.

For related information, see the Psychiatric News article “The Ketamine Challenge: When Practice Leaps Ahead of Science.”

(Image: Hospira, Inc.)

Wednesday, September 30, 2015

Combining Aripiprazole, Venlafaxine Reduces Depressive Symptoms in Older Adults

Adding a low dose of the antipsychotic aripiprazole to the antidepressant regimen of older adults with treatment-resistant depression may help them achieve and sustain remission, according to a study published yesterday in the Lancet.

Previous studies show that more than half of older adults with major depressive disorder fail to respond to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). In the current study, Charles Reynolds, M.D. (pictured left), a professor of geriatric psychiatry at the University of Pittsburgh School of Medicine, and his colleagues tested the effectiveness and safety of aripiprazole as an adjunctive therapy to venlafaxine in 468 adults aged 60 and over with no history of cognitive deficits.

Each study participant received an extended-release formulation of venlafaxine—ranging from 150 mg per day to 300 mg per day—for 12 weeks. Of the 181 patients whose symptoms did not remit after 12 weeks of treatment, 91 were randomly assigned to receive venlafaxine for another 12 weeks with the addition of 10 mg to 15 mg of aripiprazole and 90 received placebo in addition to venlafaxine each day. Remission was defined as a Montgomery Asberg Depression Rating Scale score of 10 or less (and at least 2 points below the score at the start of the randomized phase) at both of the final two consecutive visits.

The results showed that combined venlafaxine and aripiprazole therapy led to remission of depressive symptoms in 44% of treatment-resistant patients compared with 29% of participants who received venlafaxine and placebo.

Akathisia and Parkinsonism were the most common adverse events reported by participants in the aripiprazole adjunctive therapy group, occurring respectively in 26% and 17% of those patients. No differences were reported between groups in changes in percentage of body fat, or in total cholesterol, HDL, LDL, triglycerides, glucose, or insulin concentrations.

“Our results showed that aripiprazole is moderately effective in older adults with treatment-resistant depression,” the authors wrote. “Clinicians prescribing this medication should be aware of its propensity to cause akathisia and Parkinsonism. However, the potential benefits of remission from depression and greater reductions in suicidal ideation outweigh these usually mild adverse events.”

To read more about treating older adults with depression, see the Psychiatric News article “Older Adults Are More Likely to Receive Prescriptions for Depression, Anxiety.”

Human Rights Expert to Be Keynote Speaker at APA’s Meeting in NYC

Adeyinka M. Akinsulure-Smith, Ph.D., is a licensed psychologist from Sierra Leone who has participated in human rights investigations in Sierra Leone, worked with war victims from the African diaspora and survivors of torture, and served as an expert on gender crimes and posttraumatic stress disorder in a case before the International Criminal Court. She will discuss her work and experiences on Thursday, October 8, at IPS:The Mental Health Services Conference, which is being held at the Sheraton New York Times Square Hotel. Learn more about the meeting and register now.

(Top image courtesy of University of Pittsburgh School of Medicine)


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