Cardiovascular Safety of Amphetamine/Dextroamphetamine versus Methylphenidate in Older Adults.

Background: Recent epidemiological data has shown a sharp increase in stimulant use among older adults, which is notable as older adults may be especially vulnerable to their cardiovascular effects. Results of recent studies have shown an increase in cardiovascular events among older adults using stimulants; however, little data exists comparing cardiovascular safety of these agents head-to-head. Objective: To determine if the incidence of serious cardiovascular events, including myocardial infarction (MI), stroke/transient ischemic attack (TIA), or arrhythmia, are different in patients taking amphetamine/dextroamphetamine compared with patients taking methylphenidate. Methods: Retrospective chart review of veterans 50 years and older at the Veterans Affairs North Texas Health Care System (VANTHCS) who were first prescribed a stimulant between 2015 and 2021. The primary outcome was the difference in composite cardiovascular events between amphetamine/dextroamphetamine and methylphenidate. Secondary outcomes were the composite cardiovascular endpoints compared individually (MI, stroke/TIA, or arrhythmia). Hazard ratios were calculated based off of a time-to-event analysis displayed using a Kaplan-Meier curve for primary and secondary outcomes. Results: 466 veterans were screened for inclusion, 30 were excluded, and 436 were included. There was no difference found in composite cardiovascular events between the 241 veterans in the amphetamine/dextroamphetamine group and the 195 veterans in the methylphenidate group with 12 (5%) vs 8 (4.1%) events respectively (P = .6635). There was also no difference in time-to-event analysis (P = .4966). Conclusion: In elderly veterans, there was no difference found in incidence of major cardiovascular events with the use of amphetamine/dextroamphetamine compared with methylphenidate.

A Review of Therapeutics for Treatment-Resistant Depression in the Older Adult.

One-third of older adults with depression meet criteria for treatment resistance, typically defined as a lack of response to two or more adequate trials of an antidepressant. Treatment resistance contributes to an unfavorable prognosis, compromised medical outcomes, heightened disability, accelerated cognitive decline, and an elevated risk of developing dementia. Despite this significant morbidity, evidence is sparse for how to proceed with treatment in this population. Non-pharmacologic therapy (e.g., diet, psychotherapy) can be utilized as adjunctive therapy, despite little published evidence of benefit, given that the risks are low. Pharmacotherapy trials in the treatment-resistant late-life depression population lack strong methods and external validity; however, the use of venlafaxine as monotherapy and add-on therapy, as well as lithium, bupropion, or aripiprazole as add-on therapy to standard antidepressant therapy, have enough evidence that a trial with appropriate monitoring is a prudent strategy. Electroconvulsive therapy remains a well-studied safe therapy, especially when used as maintenance treatment once an initial cycle is completed but is traditionally underutilized in the treatment-resistant late-life depression population. Ensuring non-pharmacologic and pharmacologic strategies are optimized and given a sufficient trial in those with treatment-resistant late-life depression is the best we can do for this vulnerable population.

An Evaluation of Nonacademic Predictors of Success in a Doctor of Pharmacy Program.

Objective. Pharmacy programs have struggled to predict who will be successful in their programs based solely on cognitive skills. The primary objective of this study was to determine which, if any, nonacademic factors are associated with on-time progression within the school of pharmacy curriculum.Methods. A survey was developed and offered to all Texas Tech University Health Sciences Center Jerry H. Hodge School of Pharmacy students in fall 2020. This survey included questions to collect demographic data and incorporated four validated questionnaires: the Grit-Grid, the Academic Pharmacy Resilience Scale (APRS-16), the Cohen Perceived Stress Scale (CPSS), and the Turkish Time Management Questionnaire (TTMQ).Results. Completed surveys were submitted by 213 students out of 569 (37.4% response rate). On-time progression rate was calculated separately for each class. Through binary logistic regression, we found that on-time progression was significantly associated with prepharmacy grade point average >3.20, high school Grit-Grid score >0.9, APRS-16 score >35, and CPSS score >34. Pharmacy College Admission Test (PCAT) composite scores and admissions committee rubric scores were not associated with on-time progression.Conclusion. Based on the results of this study, it may be reasonable to implement the Grit-Grid, APRS-16, and the CPSS in the admissions process to help determine the most appropriate candidates for our program or use them as screening tools for incoming students to identify who may be at academic risk. However, these factors need to be validated in pharmacy programs in other private and public universities before widespread adoption can be condoned.

Comparison of lithium to second generation antipsychotics for the treatment of bipolar disorder in older veterans.

Approximately 25% of all adults with bipolar disorder are over the age of 65. Literature in older age bipolar disorder is sparse and typically extrapolated from data in younger adults. This retrospective cohort study included patients 65-89 years of age with bipolar I or II disorder who were prescribed lithium or SGA treatment. Primary efficacy outcome was defined as time to discontinuation of treatment and numerous secondary safety outcomes were included such as adverse effects; lab changes; mental health related hospitalizations; and death. No difference was found between the lithium group and the SGA group in days until discontinuation.

Pharmacologic management of behavioral and psychological symptoms of major neurocognitive disorder.

Behavioral and psychological symptoms of dementia (BPSD) occur in approximately 80% of patients who receive a diagnosis of major neurocognitive disorder. Nonpharmacologic strategies are the first-line treatment for BPSD. However, psychotropic medications are often necessary when nonpharmacologic methods are not effective in treating symptoms that are distressing or are causing behaviors that are dangerous to the patient or the patient's caregivers. The article provides a review of evidence-based recommendations for the use of antipsychotics, cognitive enhancers, and serotonin reuptake inhibitors for the treatment of BPSD. Different pharmacologic approaches are demonstrated through 2 patient cases in which nonpharmacologic management was not effective. The severity of BPSD must be weighed against the risks and benefits of pharmacologic intervention in order to implement an optimal medication regimen.

Antipsychotic discontinuation after the initiation of selective serotonin reuptake inhibitors therapy for the treatment of behavioral and psychological symptoms associated with dementia.

INTRODUCTION: Antipsychotics are used off label to treat behavioral and psychological symptoms of dementia (BPSD). Due to the emerging data of selective serotonin reuptake inhibitors (SSRIs) for treatment of BPSD, clinicians may choose to use this medication class instead of antipsychotics when pharmacologic therapy is necessary. The objective of this study was to evaluate the prevalence of antipsychotic discontinuation 6 months after SSRI initiation for the treatment of BPSD. METHODS: Patients with Alzheimer dementia who were prescribed an antipsychotic and later prescribed an SSRI for BPSD during January 1, 2009, through December 30, 2014, were studied. Exclusion criteria included (1) a dementia diagnosis besides Alzheimer; (2) scheduled benzodiazepines, mood stabilizers, or non-SSRI antidepressant use during the study period; (3) diagnoses of bipolar or psychotic disorders; and (4) diagnosis of delirium during the study period. Patients' age, sex, race, and functional assessment of staging for Alzheimer disease scores were collected. The names, doses, and stop dates of SSRIs and antipsychotics were also recorded. RESULTS: Thirty-six patients were included in the analyses. Overall, antipsychotic use was reduced in 11 patients (30.6%). Ten patients (27.8%) discontinued the antipsychotic, and 1 additional patient had a reduction in dose. When comparing specific SSRIs, 8 (72%) responders were prescribed citalopram, and 15 (60%) nonresponders were prescribed sertraline. DISCUSSION: Approximately 30% of patients with Alzheimer dementia who were prescribed antipsychotics for BPSD were able to discontinue the medication or had a dose reduction after starting SSRI therapy. Most SSRI responders were prescribed citalopram.

The Impact of Cholinesterase Inhibitors with or without Memantine on Antipsychotic Prescribing.

Background Alzheimer's disease (AD) medications have been suggested to positively affect behavior, though not universally in all studies. Their impact on antipsychotic use is not well-defined. Methods This cross-sectional, retrospective study evaluated residents with AD on cholinesterase inhibitors, memantine, both, or neither throughout multiple long-term care facilities during July 2014. Patients were included if they: were between 65 and 89 years of age, had a diagnosis of AD, and had a cognitive assessment within three months of the study period. Patients residing in the facility for 100 days or fewer, or those having a Centers for Medicare & Medicaid Services-approved diagnosis for antipsychotic use were excluded. The primary outcome was the prevalence of antipsychotic prescribing in patients receiving AD medications compared with those without AD therapy. The Texas Tech University Health Sciences Center institutional review board approved the study protocol. Results Of 1,282 patients screened, 285 (161 AD medications and 124 no-AD medications) were analyzed. Median cognitive status scores suggested severe cognitive impairment. Patients receiving AD medications had higher antipsychotic utilization compared with those without AD medications (27% vs. 19%, respectively; P = 0.08). Patients receiving combination AD medications had the highest antipsychotic use. No statistically significant differences were detected in cognitive status subgroups. Of interest is that a post-hoc analysis found a statistically significant association with greater antipsychotic use and increasing number of AD medications. Conclusion Long-term care facility residents with AD receiving AD medications had higher rates of antipsychotic use compared with those not receiving AD treatment. The link between antipsychotic use and the number of AD medications may point to overprescribing in dementia with behavioral disturbances as a potential contributing factor.

Antidepressant Exposure and Risk of Dementia in Older Adults with Major Depressive Disorder.

OBJECTIVES: To identify whether duration of antidepressant use in depressed elderly veterans differed between those who later developed dementia and those who did not. DESIGN: Single-center, retrospective, observational, electronic chart review. SETTING: Medical charts from a Veterans Affairs Mental Health Clinic. PARTICIPANTS: Veterans aged 65 and older with history of depression. MEASUREMENTS: Information on sociodemographic characteristics; duration of antidepressant, antipsychotic, and benzodiazepine therapy; diagnosis of dementia; and comorbid disease states was collected. Medication use since August 1, 1998 was recorded. RESULTS: Of 1,547 charts reviewed, 605 met inclusion criteria; 128 were excluded on the basis of psychiatric comorbidities. Of the remaining 477, 41 developed incident dementia. Thirty-seven of those were matched to individuals with depression without dementia according to age, cardiovascular disease, cerebrovascular disease, diabetes mellitus, and substance use. There were no differences between the groups with (n = 37) and without (n = 37) dementia with respect to baseline characteristics, antidepressant types, or benzodiazepine or antipsychotic use. Median duration of antidepressant use was 891 days in the group with dementia and 1,979 days in the group without (P = .03, W = -260, z = -2.13). Significantly fewer participants with dementia received antidepressant treatment for at least 5 years [n = 8 with dementia, n = 20 without dementia, P = .004, odds ratio = 0.235, 95% confidence interval = 0.085-0.647). CONCLUSION: Older veterans with depression who developed dementia were treated with antidepressants for a significantly shorter duration than matched veterans who did not develop dementia.

Evaluation of QTc prolongation and dosage effect with citalopram.

INTRODUCTION: Recently, controversy has surrounded a 2011 Food and Drug Administration warning against using citalopram at doses >40 mg/day due to QTc prolonging effects. METHODS: Patients ≥18 years old at the VA North Texas Health Care System were included in this retrospective review if they had received at least 1 prescription for a 30-day supply of citalopram between January 1, 2007, and February 29, 2012, and had a baseline electrocardiogram (ECG) within 1 year before initiation or dose increase of citalopram and at least 1 repeat ECG within 3 months after citalopram initiation or dose increase. The primary endpoint was the prevalence of QTc prolongation (QTc interval ≥470 ms for men and ≥480 ms for women) after initiation or a dose increase of citalopram. For secondary objectives, Fisher exact tests were used determine if there was a dose-dependent difference in prevalence of QTc prolongation among the whole study sample and among the subgroup of patients ≥60 years old. RESULTS: Among the entire study sample, QTc prolongation was identified in 12 patients (16.4%) after initiation or a dose increase of citalopram. In the subgroup of patients ≥60 years old, QTc prolongation was identified in 7 patients (21.9%). Prevalence of QTc prolongation increased with dose in the entire study population (P = .016) and in patients ≥60 years (not significant). DISCUSSION: This retrospective study suggests that citalopram produces a dose-dependent increase in QTc interval.

Effect of pharmacy students as primary pharmacy members on inpatient interdisciplinary mental health teams.

PURPOSE: The effect of pharmacy students as primary pharmacy members on inpatient interdisciplinary mental health teams was investigated. METHODS: This retrospective study used Veterans Affairs data from veterans who were admitted to an inpatient mental health unit from January 1, 2010, through December 31, 2012. Eligible veterans had to have been hospitalized for at least five days and treated with at least five scheduled medications during the hospitalization. Information collected by the investigators included patient age, psychiatric diagnoses, accuracy of medication reconciliation on admission and at discharge, and readmission rates within six months and one year. Additional information collected included monitoring parameters for lithium, divalproex, first-generation antipsychotics, and second-generation antipsychotics. The primary outcome was the percentage of accurate medication reconciliations for treatment teams with a fourth-year pharmacy student and without a pharmacy student. Clinical monitoring and readmission rates were also compared. RESULTS: A total of 526 patients were eligible for study inclusion. Medication reconciliation was performed on admission for all patients followed by a team involving a pharmacy student (experimental group), but only 51% of patients in the control group had documented medication reconciliations in the medical chart. Of the medication reconciliations completed, 82% were performed correctly in the experimental group, compared with 61% when a pharmacy student was not involved (p = 0.006). There were no significant differences between groups in psychotropic monitoring and readmission rates. CONCLUSION: The presence of fourth-year pharmacy students on inpatient mental health interdisciplinary teams was associated with more frequent interventions, patient counseling, and medication reconciliation, compared with rates for teams without a pharmacy student. Medication reconciliation was performed more consistently and accurately when the teams had a pharmacy student than when they did not.

Visual hallucinations treated with the reinitiation of memantine in a patient with Lewy body dementia.

OBJECTIVE: To report on a patient with Lewy body dementia who developed worsening of hallucinations with memantine withdrawal and significant improvement with reinitiation of the drug. CASE SUMMARY: A 78-year-old man presented to a geriatric psychiatry clinic in March 2011. The patient had experienced gradual memory loss since 2007 and was diagnosed with dementia with Lewy bodies (DLB) in 2009. His medication regimen included donepezil and memantine; his cognitive and functional status appeared stable. Occasional mild visual hallucinations occurred but were not concerning to the patient or his wife. The patient did well to July 2011, when memantine became restricted within the health care institution; memantine was therefore tapered to discontinuation. From July to September 2011, the patient's cognition and function appeared to decline significantly. He also began experiencing severe visual hallucinations daily. Memantine was reinitiated in September 2011 and, within days, the patient was free of hallucinations. By November 2011, his cognition and function were noted to have improved to previous status, and hallucinations were rare. DISCUSSION: Three small randomized studies and 4 case reports were found addressing the use of memantine for DLB. Both improvement and worsening of hallucinations were noted with memantine use in the case reports, but the studies showed only a small benefit in cognition. However, cognitive and psychiatric symptoms worsened when memantine was discontinued. One study found that Neuropsychiatric-Inventory scores and hallucination scores improved significantly for patients taking memantine. CONCLUSIONS: The literature investigating the use of memantine for the psychiatric symptoms of DLB is limited but there are data noting results similar to what we observed in our patient when his memantine was discontinued and reinitiated.

Targeting treatment-resistant depression.

Only 50% of depressed patients achieve remission of symptoms after 2 trials of antidepressants. Therefore one half of patients are considered treatment resistant. Studies have shown that with each failed antidepressant, chances of remission continue to decline. Untreated depressive symptoms lead to impaired social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization. Clinicians recognize there is an urgent need to find an efficacious treatment, but it becomes more difficult to decide on an appropriate therapy once a patient has failed 2 to 3 trials of antidepressants. An evidence-based review was performed to assess the efficacy and safety of several different antidepressant strategies to help the clinician decide which may be beneficial for specific patients.

Incidence of abnormal metabolic parameters and weight gain induced by atypical antipsychotics in elderly patients with dementia.

OBJECTIVE: To determine if atypical antipsychotic therapy leads to the development of abnormal metabolic parameters and weight gain in elderly patients with dementia. DESIGN: Retrospective chart review. SETTING: Veterans Affairs Medical Center. PATIENTS: Veterans 65 years of age or older with the diagnosis of dementia. MAIN OUTCOME MEASURE: The incidence of impaired fasting glucose (> 100 mg/dL) after initiation of atypical antipsychotic therapy. The secondary objectives were to determine the incidence of significant weight gain, worsening of lipid values, new onset of type 2 diabetes mellitus, and metabolic syndrome. RESULTS: After reviewing 979 charts for inclusion and exclusion criteria, 56 patients were found eligible for the study. More than 50% of patients were excluded because they were lacking baseline or follow-up glucose laboratory results. Ten percent of the study population developed impaired fasting glucose after starting atypical antipsychotic therapy. Overall glucose increased by 9.7 mg/dL from baseline to follow-up. Significant weight gain (>or= 7% of baseline weight) occurred in 8.92% of elderly. However, overall weight decreased by 1.3 kg during the study periods. Patients who developed worsening lipid parameters or were started on lipid-lowering therapy were 14.5% of the study population even though overall lipid levels improved or remained unchanged. CONCLUSION: Periodic monitoring of glucose should be considered for patients with dementia begun on atypical antipsychotics, although aggressive monitoring may be controversial for end-stage dementia. Overall, weight reduction and improvement in lipid parameters were observed in this study. The common metabolic adverse effects noted frequently with atypical antipsychotics may not be as much of a concern with the elderly population.

Pharmacologic agents for the treatment of obesity.

Obesity guidelines state that pharmacologic therapy can be considered if a patient fails to lose 10 percent of their original body weight after 6 months of adhering to a low calorie diet, exercise, and behavior modification. Many published trials have shown sibutramine and orlistat to be effective for weight loss and weight maintenance when used with lifestyle modifications. However, few trials have studied the efficacy and safety of these medications in the elderly. This article provides a review of the FDA approved medications currently available for the treatment of obesity. Pertinent clinical trials are also reviewed and recommendations regarding the use of these agents in the elderly are discussed.