Ryan M. Carnahan

The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity.

Anticholinergic Drug Scale (ADS) scores were previously associated with serum anticholinergic activity (SAA) in a pilot study. To replicate these results, the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long‐term care facility residents who were not included in the pilot study. Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects. In the replication analysis, ADS scores were significantly associated with SAA (R 2 = .0947, P <.0001). In the modification analysis, each model significantly predicted SAA, including ADS scores (R 2 = .0741, P <.0001). The modifications examined did not appear useful in optimizing the ADS. This study replicated findings on the association of the ADS with SAA. Future work will determine whether the ADS is clinically useful for preventing anticholinergic adverse effects.

The association of weight gain and olanzapine plasma concentrations

Abstract: Atypical antipsychotics, including olanzapine, have been associated with clinically significant weight gain in some patients. The purpose of this study was to determine if weight gain was associated with increasing plasma concentrations during olanzapine treatment in subjects with schizophrenia. This study included 39 acutely ill subjects with schizophrenia, schizoaffective disorder, or schizophreniform disorder (DSM-III-R or DSM-IV). Assessments included the Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a dose of 5 to 20 mg/d for 2 to 6 weeks. A 24-hour plasma concentration was obtained after 6 weeks of treatment. Analysis using a receiver operator characteristic curve identified a threshold dose-weighted plasma concentration of 20.6 ng/mL being associated with an increased likelihood of clinically significant weight gain (≥7% baseline weight) during olanzapine treatment. The associations remained significant after adjusting for age, gender, baseline body mass index, baseline symptom severity, and symptom improvement (OR = 10.1; 95% CI, 1.3-75.0; P = 0.024). Similar analysis determined that a threshold olanzapine dose of 13.3 mg/d was associated with ≥7% weight gain. However, after adjusting for potential confounders, the results did not remain significant. The association of weight gain with plasma concentrations during treatment with olanzapine may support the utilization of plasma drug concentration as a marker for antipsychotic-induced weight gain in the treatment of schizophrenia.

Increased risk of extrapyramidal side‐effect treatment associated with atypical antipsychotic polytherapy

Objective:  To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side‐effects (anti‐EPS drugs) and whether the risk is attributable to antipsychotic dose.

Hypomania with Agitation Associated with Varenicline Use in Bipolar II Disorder

TO THE EDITOR: Varenicline is an α4β2 nicotinic receptor partial agonist approved for smoking cessation.1 We report a case of probable hypomania due to initiation of varenicline therapy in a woman diagnosed with bipolar II disorder. Case Report. A 41-year-old white woman with a history of bipolar II disorder and polysubstance abuse presented to the hospital with irritability and suicidal ideation. She reported abstinence from alcohol for 3 months and from methamphetamine for 3 years. Her medications at the time of admission included bupropion XL 300 mg every morning, clonazepam 1 mg at bedtime, oxcarbazepine 150 mg every morning and 300 mg at bedtime, quetiapine 100 mg as needed for insomnia, montelukast 10 mg, and pantoprazole 40 mg every morning. With the exception of clonazepam, which had been started 5 months prior to her admission, she had taken these medications for more than a year. She was also taking varenicline 1 mg twice daily, started approximately 1 month prior. She smoked 2 packs of cigarettes per day and made several unsuccessful attempts to quit with nicotine replacement formulations and bupropion. The patient was otherwise healthy—all laboratory test results were within normal limits. Using the recommended titration schedule, the woman had found that, within 2 days of starting varenicline, cigarettes had begun to taste unpleasant, and she decreased her amount of smoking. However, she also reported that, after 3 days of taking varenicline, she became irritable, her “skin crawled,” and she felt “wacko.” At that point, she decided to discontinue taking the drug. She reported that upon discontinuation of varenicline, those symptoms resolved. A few days later, she developed a “head cold” which she treated with over-the-counter products, including vitamin C and Alka Seltzer Cold (which contains a decongestant and an antihistamine). When the cold reinforced her desire to quit smoking, she decided to restart varenicline. She became increasingly irritable and angry and was sleeping only about 2 hours a night. Her symptoms continued for several weeks, at which point she had a fight with her husband and made a suicidal gesture. She reported crying uncontrollably and feeling so tense that she felt that her “body was crawling”; she also scratched her arms and pulled clumps of hair from her head. At that point she was admitted to the hospital due to suicidal ideation, feelings of hopelessness and irritability, insomnia, agitation, and racing thoughts. Her psychiatrist, who had treated her for approximately 10 years, diagnosed a hypomanic episode with suicidal ideation. By the patient’s own report, she had experienced a similar episode 10 years prior to this. Varenicline was discontinued; quetiapine dosing was changed to 25 mg 3 times per day as needed for agitation and 50 mg at bedtime for sleep; guanfacine 1 mg every night was added for explosive anger. Her symptoms improved greatly and she was discharged 3 days later. Discussion. Alternatives to varenicline’s being the cause of the patient’s symptoms include (1) nonadherence to drug therapy (the patient asserted that she had been taking her medications as directed and nothing suggested otherwise), (2) illicit drug use (she reported abstinence from illicit drugs and alcohol; a urine drug screen was positive for cannabis, but she was discharged before the results were known and was unavailable to respond), and (3) nicotine withdrawal (the timing of the symptoms went beyond that expected if withdrawal were the culprit; nicotine withdrawal symptoms are generally short-lived and the patient’s symptoms lasted at least a month). The Naranjo criteria indicated a probable association of varenicline with this episode of hypomania.1 Psychiatric complaints such as insomnia (20.9–33.9%), irritability (21%), and abnormal dreams (11.6–19.4%) were reported as adverse events in clinical trials of varenicline, but those trials were conducted in nonpsychiatric populations.2,3 We identified one published case of a manic episode4 and another of an exacerbation of schizophrenia associated with varenicline.5 Recently, the Food and Drug Administration sent out a safety alert informing healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken varenicline.6 With the widespread use of smoking cessation products in psychiatric populations, it is important that providers be made aware of the potential for psychiatric adverse effects with this medication.

Dementia and Comorbidities: An Overview of Diagnosis and Management

The term “dementia” describes various neurodegenerative disorders that effect cognition, including Alzheimer disease, vascular dementia, and others. This article reviews the diagnosis and management of common types of dementia and comorbidities. Dementias are differentiated clinically by history, symptom presentation, and exclusion of other causes through laboratory and imaging studies. Cholinesterase inhibitors are useful but may not be effective for all types of dementia and provide only modest benefits. Certain medical comorbidities may increase the risk of dementia, although genetics are also important in its etiology. Psychiatric comorbidities in dementia include delirium, which is treated primarily by addressing underlying medical disorders, but antipsychotics can be useful for symptom management and patient comfort. Nonpharmacologic interventions are first-line treatments for other psychiatric comorbidities, although drug therapy may be useful in some cases. The management of patients with dementia presents many challenges and will continue to do so unless agents with pronounced disease-modifying capabilities are developed.

Exacerbation of panic disorder with rifampin therapy in a patient receiving citalopram.

Citalopram, a selective serotonin reuptake inhibitor, is used in the management of anxiety disorders. A 55‐year‐old man receiving citalopram for panic disorder reported a decrease in the agents therapeutic efficacy when rifampin was started for osteomyelitis. His condition improved when the rifampin was stopped. Rifampin is known to induce the metabolism of cytochrome P450 3A4 substrates and thus plays a role in several drug‐drug interactions. We suspect that the efficacy of citalopram was blunted with the concurrent use of rifampin. To our knowledge, only one other case of an interaction of rifampin with a selective serotonin reuptake inhibitor is described in the literature. Clinicians should monitor all drugs and dietary supplements that patients with psychiatric conditions take, regardless of the indication, intended purpose, or prescriber. This is especially important, however, for a drug that is pivotal to a patients well‐being; its therapeutic effect should be carefully monitored when any new drug is added or a change in the dosage of a concurrent drug is made.

Antipsychotic Medication Use in the Elderly Patient

The use of antipsychotic medications in the elderly can be very complex and is ever changing. Consideration must be given to not only the physiologic and functional changes normally associated with age but also to the latest data on safety and adverse outcomes associated with using these agents. Because of new and changing information, this article will review the effects of aging, side effects of antipsychotic medications, and the current issues surrounding their use in elderly patients for those clinicians who are not specialists in this area of practice.

Clostridium difficile-associated diarrhea in a tertiary care medical center

This retrospective, case-control study aimed to identify variables associated with the incidence of Clostridium difficile–associated diarrhea (CDAD) in acute care facilities and to specifically identify the relationship of fluoroquinolones and acid suppressive agents in the development of CDAD. Seventy-one symptomatic patients positive for C. difficile toxin A or B hospitalized for at least 72 hours were compared with 142 control patients hospitalized for at least 72 hours who were not positive for C. difficile toxin A or B. Two controls were matched to one case patient for age within 5 years, unit of admission, and date of admission. The mean ages for cases and controls were 63.5 and 62.7 years, respectively. After adjusting for two confounding variables—hospital stay within 3 months and Charlson Comorbidity Index—conditional multiple logistic regression identified six risk factors for development of CDAD: gastrointestinal procedures within 60 days (odds ratio [OR] 9.1, P < 0.013), levofloxacin exposure (OR 8.2, P < 0.033), moxifloxacin exposure (OR 4.1, P < 0.026), imipenem exposure (OR 14.9, P < 0.014), laxative use (OR 20.2, P < 0.0001), and immunosuppressive use (OR 20.7, P < 0.034). The risk of CDAD after exposure to levofloxacin or moxifloxacin was not significantly different. Acid suppressive therapy was not a risk factor for CDAD development.

Consistency of antidepressant and chronic nonpsychiatric medication use in a high-risk clinical population

BACKGROUND Antidepressant nonadherence is a significant threat to clinical outcomes and can be divided into 2 primary domains, persistence and consistency. Although antidepressant persistence has been well described, little is known about consistency patterns. OBJECTIVES The primary objective of this study was to characterize consistency among persistent antidepressant users. Patients with depression may also exhibit poor adherence to medications for chronic comorbid conditions. Thus, a second objective was to compare their consistency with chronic, nonpsychiatric medications with that of nonantidepressant users. METHODS Continuously eligible adult patients were selected from the Iowa Medicaid Pharmaceutical Case Management program based on receiving an antidepressant or a selected chronic nonpsychiatric medication for at least the first 4 months after program enrollment. Consistency over the first year of enrollment was determined from prescription refill patterns, using the MED-OUT index. RESULTS The mean consistency rate was 86% among the 1122 persistent antidepressant users. Consistency was not significantly different among polyantidepressant users or across the antidepressant classes. Among antidepressant users, consistency with antidepressants was not significantly different from consistency with chronic nonpsychiatric medications. Antidepressant users were not significantly less consistent with chronic nonpsychiatric medications than nonantidepressant users, after controlling for the confounding factors of age, sex, and total number of medications. CONCLUSIONS Consistency with medications in this population of persistent antidepressant users with medical illnesses was fairly good, and comparable to that of nonantidepressant users. The unique population may have influenced consistency rates. Focusing on persistent antidepressant users may have limited the expected impact of depression on medication consistency.

Premorbid Intellect and Current RBANS Performance: Discrepancy Scores in Three Geriatric Samples

Assessing cognitive change during a single visit requires the comparison of estimated premorbid abilities and current neuropsychological functioning. As newer instruments are developed to measure current cognitive functioning, their relationships with premorbid estimates need to be evaluated. The current study examined the clinical utility of discrepancy scores between an estimate of premorbid intellect derived from demographic variables (i.e., Barona) and the Total score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in three geriatric samples. A large community-dwelling “control” sample and two clinical samples were examined. As expected, there was little difference between estimated premorbid intellect and current RBANS Total Scale scores in the community-dwelling sample, while estimated premorbid intellect obtained from the two clinical samples significantly differed from obtained RBANS Total scores. Similar findings were observed on Discrepancy scores for the five Indexes of RBANS. The current findings, along with normative data on these discrepancy scores, can provide additional confidence for clinicians and researchers who need to determine cognitive decline when using these screening measures of neuropsychological status.