American Association for Geriatric Psychiatry (AAGP) 2013 Annual Meeting
March 14-17, 2013; Los Angeles, CA
Study Indicates Cognitive Impairment Does Not Increase Pharmacotherapy Needed to Achieve Depression Remission
Recent research has shown a strong association between late-life depression (LLD) and increased risk for all-cause dementia, Alzheimer’s disease, and vascular dementia. Studies have also shown that when LLD occurs in the context of an existing cognitive impairment, it tends to persist even after treatment with antidepressant medications. However, during a presentation at this year’s AAGP annual meeting, Aaron Koenig MD, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, and colleagues reported on a series of analyses that showed that the presence of cognitive impairment or dementia in adults with LLD is not necessarily indicative of poor pharmacotherapy response. In the study, patients with mild cognitive impairment or dementia showed a similar ability to achieve remission of LLD as cognitively intact individuals.
Koenig and colleagues retrospectively reviewed data from the acute treatment protocol of the MTLD-III (Maintenance Therapies in Late-life Depression-III) study, which was a randomized, double-blinded, placebo-controlled trial that assessed the efficacy of adjunctive donepezil as part of maintenance treatment for LLD. Participants in the trial completed an acute treatment protocol before entering the placebo-controlled phase of the study. This protocol consisted of three treatment steps. First, participants were treated with escitalopram, a selective serotonin reuptake inhibitor (SSRI). If SSRI treatment did not lead to remission, participants were switched to the serotonin–norepinephrine reuptake inhibitors venlafaxine or duloxetine. Finally, as a third step, participants could receive add-on aripiprazole. In addition, concurrent low-dose benzodiazepines were administered for anxiolytic or hypnotic purposes on an as-needed basis. The purpose of this protocol was to help participants achieve remission of their depressive symptoms, as indicated by scores of 10 or less for 3 consecutive weeks on the Hamilton Rating Scale for Depression (HRSD).
A total of 153 participants completed the acute treatment protocol, and Koenig and colleagues divided these individuals into three groups based on their cognitive status: normal cognitive function (n=74), mild cognitive impairment (n=60), and dementia (n=19). They then proceeded to evaluate how many treatment steps each group needed to reach remission, the average length of time each group required to reach remission, and the proportion of participants in each group requiring concurrent benzodiazepines for anxiolytic or hypnotic purposes. They also assessed weekly HRSD scores to identify patterns of response for each cognitive profile.
Koenig and colleagues found no statistically significant differences between cognitive groups in the number of treatment steps needed to achieve remission of LLD (P=.68) or in the proportion of subjects requiring concurrent benzodiazepines (P=.79). In addition, they were surprised to find that a greater proportion of participants with dementia (73.7%) responded to first-line treatment than those who were cognitively intact (58.1%) or had mild cognitive impairment (56.7%). All groups also demonstrated a similar mean time to remission, which occurred at 22.4 weeks, 22.8 weeks, and 21.7 weeks for participants with dementia, mild cognitive impairment, and normal cognition, respectively.
“These data indicate that patients with mild cognitive impairment or dementia do not necessarily need more intense pharmacotherapy to treat their depression to remission, as compared with cognitively intact patients,” said Koenig in an interview with Clinical Geriatrics.® “In fact, our study suggests that depression severity at the start of treatment and longer depressive episode duration seem to correlate more strongly with antidepressant response variability than with cognitive function, at least in short-term treatment. However, physicians should tailor their treatment approach to the individual patient and take into account all available data when making treatment decisions,” Koenig noted.
One study limitation was a lack of complete data on participants who dropped out of the study before completing the acute treatment phase. “We can’t discount that our results may have been influenced by selection bias, such that individuals who didn’t respond to treatment may have had greater propensity to drop out of the study prior to completion,” Koenig said. “In addition, this was an open-label trial, so we don’t know if the subjects who responded to pharmacotherapy would have responded just as well to placebo. And this really prevents us from saying if it was the medication that was helping these individuals remit or if it was the supportive environment of the clinic, with very close follow-up, that helped them get better,” he concluded.—Christina T. Loguidice
Study Sheds Light on Predictors of Antipsychotic Use in the Nursing Home
Although the American Geriatrics Society 2012 Beers Criteria recommend against the use of antipsychotics as a treatment for problematic behaviors associated with cognitive impairment, a poster presented by Brian M. Ludwin, BSN, and Suzanne Meeks, PhD, University of Louisville, Louisville, KY, at the AAGP annual meeting indicates that these agents are still commonly prescribed for this purpose in the nursing home setting. They also found severity of cognitive impairment to be predictive of antipsychotic use in this setting.
Ludwin and Meeks derived these conclusions by randomly selecting 280 medical records from 19 nursing homes and using the Minimum Data Set (MDS) 2.0 to retrospectively review relevant data from the 254 records that were for residents aged 65 years and older. They performed logistic regression analyses to predict the use of antipsychotics in the previous 7 days, controlling for age because previous studies reported a greater likelihood of antipsychotic use in younger patients. The severity of patients’ cognitive impairment was measured using the validated Cognitive Performance Scale, and the severity of behavioral symptoms was measured using the validated Aggressive Behavior Scale (all from the MDS 2.0).
Based on their assessments, severity of cognitive impairment (odds ratio [OR], 1.376; 95% confidence interval [CI], 1.043-1.816) and severity of behavioral symptoms (OR, 3.479; 95% CI, 1.577-7.677) were predictive of antipsychotic use. Age (OR, .958; 95% CI, .916-.1.001) was nearly predictive of antipsychotic use. In addition to these patient variables, Ludwin and Meeks observed that three of the 19 facilities included in their study accounted for 48% of all antipsychotic prescriptions.
Based on these findings, they concluded, “The results support the notion that cognition and behaviors are important drivers of antipsychotic use and that facility characteristics should be further explored as a possible issue related to this outcome.”—Christina T. Loguidice
Pseudobulbar Affect in the Nursing Home: Interview With Yadagiri Chepuru, MD
Pseudobulbar affect (PBA) is a condition characterized by episodes of involuntary, sudden, and frequent crying and/or laughing. These episodes are paroxysmal (sudden and intense), often recur several times a day, and can last from seconds to minutes. PBA is attributed to several neurological conditions that commonly affect residents of long-term care facilities, including individuals with multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, and traumatic brain injury. The symptoms can be distressing to patients and severely disruptive, leading to social phobia, withdrawal, and isolation. Clinical Geriatrics® had the opportunity to discuss PBA with Yadagiri Chepuru, MD, FAPA, chief of psychiatry, Riverside Health Care Systems, Yonkers, NY, who reviewed the condition and its treatments during a product theater at the AAGP annual meeting.
CG: How long has PBA been recognized as a clinical entity?
Chepuru: Charles Darwin first described elements of the condition more than 140 years ago in his seminal work, The Expression of the Emotions in Man and Animals, which was published in 1872. More than a decade later in 1886, Oppenheim and Siemerling introduced the term pseudobulbar affect to describe the condition. Since then, PBA has gone by a variety of terms in the scientific literature, including emotional incontinence, pathological laughing and crying, emotional lability, and post-stroke emotionality. These different labels have made it difficult to determine the true incidence and prevalence of this condition.
PBA occurs in patients with a variety of neurological conditions, but what causes it to manifest in some of these patients but not in others?
This is still unclear, but current data indicate that PBA occurs when there is disruption of the neural networks that control emotional motor expression and there is also a loss of frontal voluntary control. Autopsy reports and neuro-imaging studies have indicated that brain lesions in the cortico-pontocerebellar pathway are responsible for disrupting signaling from the cerebral cortex to the cerebellum, leading to affective dysmetria.
Is there any way to prevent PBA or determine who is at high risk of developing it?
I do not know of any way to prevent PBA from occurring, but it is important to look for PBA in patients with neurological conditions and/or brain injuries. The condition has been most commonly observed in patients with amyotrophic lateral sclerosis (estimated prevalence, 2%-53%), Alzheimer’s disease and other dementias (9%-39%), multiple sclerosis (7%-46%), Parkinson’s disease (5%-43%), stroke (6%-52%), and traumatic brain injuries (5%-48%).
In your experience how common is PBA? Is the condition underdiagnosed? If so, why?
The medical literature suggests that PBA is an underrecognized and underdiagnosed condition. Currently, the largest observational study to have assessed the prevalence of PBA symptoms is the PBA Registry Series (PRISM), which found that 27.6% of all neurological patients have PBA symptoms. Low patient awareness, confusion with depression, and reluctance to discuss PBA symptoms due to embarrassment are some of the contributing factors for underrecognition and underdiagnosis of this condition.
How do you distinguish PBA from mood disorders like depression?
PBA is often mistaken for depression, but they are quite different. Crying is a predominant emotional expression in depression, and the patient’s mood is congruent with sadness, which can last for weeks to months. Patients with depression also commonly experience feelings of hopelessness, worthlessness, guilt, and thoughts of death, and these feelings may lead to changes in sleep and appetite. Finally, these patients may not have an underlying neurological disorder. In contrast, patients with PBA have an underlying neurological condition or injury and express emotions that are not congruent with the emotions they are feeling, so they may cry despite feeling happy or laugh when they feel sad. The emotions in these patients tend to be sudden and unpredictable, and they do not stem from a mood disorder; however, PBA and depression can coexist in some patients.
Once PBA is diagnosed, how is it treated?
Historically, because crying is a common emotional expression with PBA, many patients have been treated rather unsuccessfully with antidepressants. However, in October 2010, the FDA approved Nuedexta (dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg) as the first treatment specifically for PBA. Nuedexta is dosed at one capsule daily for the first 7 days and then increased to two capsules daily thereafter, which are given 12 hours apart. I have found this agent to be very effective in controlling PBA symptoms in my patients.
Is Nuedexta contraindicated in any patients?
The agent should not be given to patients with hypersensitivity to the drug or any of its components. It also should not be used in patients receiving quinidine or related agents; monoamine oxidase inhibitors; or any drugs that prolong the QT interval and are metabolized by CYP2D6, such as thioridazine and pimozide. Finally, it may be contraindicated in patients with certain cardiovascular conditions, but particularly in those who have risk factors for arrhythmia. In cardiovascular patients, an electrocardiogram may be warranted before initiating treatment. As with all medications, prescribers need to carefully review the prescribing information before administering this agent.—Christina T. Loguidice
This product theater was sponsored by Avanir Pharmaceuticals, Inc.