High Dose and Extended Use of Anticholinergic Drugs May Increase Risk for Dementia, Study Suggests

Previous studies have suggested that medicines—both prescription and over-the-counter—aiming to block the actions of acetylcholine may be associated with increased risk for cognitive impairment, but a new study published this week in JAMA Internal Medicine shows that use of such medicines in older adults may increase risk for dementia.

Researchers from the Geriatric Pharmacy Program at the University of Washington led a study with over 3,400 participants, aged 65 years and older and no history of dementia at the study's initiation, to examine whether a correlation existed between cumulative anticholinergic drug use and the onset of dementia. Pharmacy-dispensing data were analyzed over a 10-year period to ascertain patients’ cumulative anticholinergic exposure.

The results showed that individuals taking daily dosages of at least 10 mgs of tricyclic antidepressants such as doxepin, 4 mgs of first-generation antihistamines such as chlorpheniramine, or 5 mgs of antimuscarinics for bladder control such as oxybutynin for more than three years were at greater risk for developing dementia than their counterparts who did not use such medicines long term.

The researchers noted that the study highlights the need to increase awareness among health care professionals and older adults about the potential risk associated with extended use of anticholinergic drugs, as well as a need for efforts to minimize such drug use. "Older adults should be aware that many medications—including some available without a prescription, such as over-the-counter sleep aids—have strong anticholinergic effects," said the study’s lead author, Shelly Gray, Pharm.D., M.S., director of the geriatric pharmacy program. "If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient," Gray stated, "they should use the lowest effective dose, monitor the therapy regularly to ensure [that] it's working, and stop the therapy if it's ineffective."

In future studies with postmortem brain tissue, the researchers plan to investigate differences, if any, of dementia-related pathology between brains that were expose long term to anticholenergic drugs and those that were not.

To read about other medicine use that has been associated with an increased risk for the dementia, see Psychiatric News article "Long-Term Use of Benzodiazepines May Be Linked to Alzheimer’s."

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Amyloid and Anxiety May Speed Cognitive Decline in Preclinical Alzheimer's, Study Suggests

High levels of anxiety concurrent with elevated amyloid beta (Aβ) levels in the brain were significantly associated with cognitive decline in healthy older adults, according to a report in JAMA Psychiatry. The results suggest that the combination could be crucial during the long preclinical phase of Alzheimer’s disease (AD). AD is known to have a preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms.

To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD, researchers at multiple institutions studied 333 healthy older adults at hospital-based research clinics. They measured levels of Aβ in the brain at baseline, and 18-, 36-, and 54-month follow-up assessments. They also used Hospital Anxiety and Depression Scale scores and comprehensive neuropsychological evaluations to measure global cognition, verbal memory, visual memory, attention, language, executive function, and visual-spatial ability.

They found that a positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function. Further, the researchers found that compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group.

“These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD,” the authors stated. “They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard anti-amyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.”

For more information on Alzheimer's research, see the Psychiatric News article, "Imaging Uncovers Brain Changes Long Before Alzheimer's Diagnosis."

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Rep. Murphy Pushes for Comprehensive MH Reform Law

Rep. Tim Murphy (R-Pa.-18) will reintroduce in Congress the Helping Families in Mental Health Crisis Act, a comprehensive reform of the American mental health system.

Murphy outlined the proposed bill as he was awarded the 2014 Torrey Advocacy Commendation by E. Fuller Torrey, M.D., founder of the Treatment Advocacy Center, at a meeting on Capitol Hill in Washington, D.C., yesterday.

“We must turn a system of pessimism, closed doors, and bureaucratic hurdles into one that embraces innovation, evidence-based care, and a spectrum of treatment options that fits the patient’s needs,” said Murphy.

In response, APA President Paul Summergrad, M.D., announced that APA’s Board of Trustees had voted unanimously last month to support Murphy’s bill.

“We hope for broad bipartisan support for something that should be above partisan politics,” said Summergrad. “APA’s psychiatric physicians will be there every step of the way to get this task accomplished.”

The bill has provisions for improving community services and integrating them with primary care, protecting access to psychiatric medications under Medicare and Medicaid, reauthorizing suicide prevention programs, and expanding research at the National Institute of Mental Health, said Murphy.

Other provisions include implementing mental health parity and monitoring its enforcement, ending the shortage of inpatient psychiatric beds, and expanding the mental health workforce.

Murphy asked for help from professional and patient groups to advocate for the legislation.

“I will not rest, nor yield, nor turn my back until we solve this problem,” he said.

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Study Finds Extended-Release Venlafaxine Effective in Spinal Cord Injury Patients With Depression

Extended-release venlafaxine was well tolerated and appears to be an effective antidepressant for decreasing core symptoms of depression and improving disability related to spinal cord injury, according to a report in JAMA Psychiatry.

Researchers at the Department of Psychiatry at the University of Washington and from several other institutions randomized 133 participants who were being treated at spinal cord injury centers to either a 12-week trial of extended-release venlafaxine or placebo using a flexible-dose algorithm. Participants were aged 18 to 64, at least one month after spinal cord injury, and diagnosed with major depressive disorder or dysthymic disorder.

Main outcome measure was score on the Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks, and on the Sheehan Disability Scale.

Statistical analyses showed a significant difference between the venlafaxine and placebo groups in improvement on the Maier subscale but not on the HAM-D. Participants receiving venlafaxine reported significantly less disability related to spinal cord injury on the Sheehan Disability Scale at 12 weeks compared with placebo. Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine group compared with the placebo group.

“Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury,” the researchers stated. “Antidepressants are used routinely to treat depression, yet no placebo-controlled trials have been published in this population to our knowledge…. Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic spinal cord injury.”

For more information, see "The Textbook of Psychosomatic Medicine: Psychiatric Care of the Medically Ill," published by American Psychiatric Publishing.

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ADHD Drug Can Reduce Binge Eating, Preliminary Study Suggests

The attention-deficit/hyperactivity disorder (ADHD) medication lisdexamfetamine dimesylate (trade name Vyvanse) may help in the treatment of binge-eating disorder, according to new clinical research appearing in JAMA Psychiatry.

The study, which carried out both safety and efficacy analyses, found that 50 and 70 mg doses of Vyvanse helped more participants curtail their binges than placebo (a 30 mg dosage had no effect). Forty-two percent of those taking 50 mg of the drug and 50 percent taking 70 mg were able to avoid excess consumption for four weeks, compared with 21 percent of the placebo group.

Nearly 85 percent of participants taking the medication experienced some form of adverse event, though, compared with around 59 percent in the placebo group. Among these cases, none of the participants in the placebo group and three in the Vyvanse group were classified as having a serious adverse event; six discontinued because of side effects. The study authors stated that the safety profile was in line with the known effects of the drug in treating ADHD, including the potential changes in heart rate. Other researchers, however, have cautioned that more work, particularly studies of long-term usage, need to be carried out.

Binge-eating is a recently recognized psychiatric disorder, having been included as a distinct category for the first time in the fifth edition of APA's Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The disorder is characterized by recurrent episodes of excessive food consumption accompanied by feelings of a lack of control.

This clinical trial was funded by Shire Development, LLC, the manufacturer of Vyvanse.

To learn more about the latest challenges and hope regarding eating disorders, see the Psychiatric News article “Expert Hopeful About Future of Treatment for Eating Disorders.”

One can also read about the current state of psychological and pharmacological treatments for eating disorders in the 5th edition of Gabbard’s Treatments of Psychiatric Disorders (chapters 30-32).

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Escitalopram Linked to Significant Improvement of Mother’s Depression and Child’s Symptoms

Previous studies have shown that when symptoms of a depressed mother remit after treatment, her offspring’s psychiatric symptoms are decreased. A study published today in AJP in Advance may shed light on some antidepressant treatment options that could lead to this domino effect.

Myrna Weissman, Ph.D., a professor of psychiatry and chief of the division of clinical and genetic epidemiology at New York State Psychiatric Institute, analyzed 76 depressed mothers and 135 offspring—aged 7 to 17—to compare which antidepressants taken by mothers would eventually lead to less psychiatric symptoms in offspring. Maternal participants were given either escitalopram, bupropion, or the combination of the two for 12 weeks. Offspring psychiatric symptoms were assessed prior to maternal initiation of therapy and at study endpoint.

Though maternal subjects in all three groups were able to achieve remission, escitalopram alone was found to be associated with statistically significant improvement in mothers' depression and subsequent improvements in offspring's psychiatric symptoms, whereas treatment with bupropion and combined bupropion and escitalopram therapy did not. In addition, mothers in the escitalopram cohort were more likely to report improvement in their ability to listen and talk to their children over the 12-weeks than mothers administered bupropion or combined therapy. Children of the escitolapram group reported their mother to be more caring after treatment.

These findings "highlight the importance of active treatment of depressed mothers, which may help them and their children," the researchers noted. "Personalizing the treatment of depressed mothers may be enhanced by assessing parental behavior and monitoring the impact on children.” The researchers concluded that antidepressants that also reduce symptoms of anxiety and irritability—like escitalopram—may be necessary to properly assess the impact of the parent’s remission on the well-being of their offspring.

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More Psychiatric Care for Minorities Could Mean Substantial Savings to Health System, Study Finds

Reducing disparities in mental health care access for racial and ethnic minorities would lead to subsequent reductions in some general medical expenditures for the same populations, said Benjamin Lê Cook, Ph.D., M.P.H., a senior scientist at the Center for Multicultural Mental Health Research and an instructor at the Harvard Medical School, and colleagues in the study "The Costs and Benefits of Reducing Racial-Ethnic Disparities in Mental Health Care" published in Psychiatric Services in Advance.

The researchers looked at data on 6,206 people with mental illness from the 2004-2010 Medical Expenditure Panel Survey. Relative to whites, African Americans and Latinos who received outpatient mental health care in one year spent less on inpatient and emergency general medical care the following year. Latinos receiving mental health care in year 1 spent less than others on inpatient general medical care in year 2. In addition, Latinos taking psychotropic drugs in year 1 showed reductions in inpatient general medical care.

The U.S. health care system would need to provide additional care to approximately 1.3 million blacks and 1.1 million Latinos with probable mental illness to eliminate disparities, wrote the researchers. “For blacks and Latinos, the potential savings in inpatient general medical expenditure are substantial (as much as $1 billion), providing preliminary evidence of a ‘business case’ for reducing disparities in mental health care access.

For more in Psychiatric News about the effect of racial and ethnic disparities in mental health, see the article "Satcher Outlines Roadmap to Reducing Health Disparities."

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