Rebecca B. Sleeper

Psychotropic Drugs and Falls: New Evidence Pertaining to Serotonin Reuptake Inhibitors

Falls are a significant cause of fatal and nonfatal injuries in older persons. Risk factors include previous falls, several disease states, and certain drugs such as tricyclic antidepressants and antihypertensives. We conducted a MEDLINE search from January 1966–March 1999 to identify studies and review articles on the association of neuroleptics, benzodiazepines, and antidepressants with fall risk in older people. The focus was on the risk associated with serotonin reuptake inhibitors, biologic plausibility, and limitations of these studies. It was thought that the agents did not increase the risk of falls, although recent evidence suggests that this is not the case.

Implications of Rosiglitazone and Pioglitazone on Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus

Clinical data suggest that thiazolidinediones—specifically, rosiglitazone and pioglitazone—may improve cardiovascular risk factors through multiple mechanisms. Low insulin sensitivity has been described as an independent risk factor for coronary artery disease and cerebrovascular disease. Patients with insulin resistance often have several known risk factors, such as obesity, dyslipidemia, and hypertension. Other emerging risk factors may be prevalent in patients with insulin resistance, such as hyperinsulinemia, elevated C‐reactive protein, elevated plasminogen activator inhibitor levels, and small, dense, low‐density lipoproteins. The only available drug class that primarily targets insulin resistance is the thiazolidinediones. These drugs have shown efficacy in affecting surrogate markers of cardiovascular risk in patients with diabetes mellitus. Alterations in these risk factors are likely due to their effects on improving insulin sensitivity and/or glycemic control. Trials to assess whether thiazolidinediones actually reduce cardiovascular outcomes are continuing.

Megestrol Acetate and Mirtazapine for the Treatment of Unplanned Weight Loss in the Elderly

A rising concern among clinicians is treatment of unplanned weight loss in the elderly, especially given the predicted growth of this population over the next few decades. Unexpected weight loss in the geriatric patient worsens overall health outcomes. A variety of pharmacotherapeutic options are available for treatment; however, evidence underlying their use is limited, and none has gained approval from the United States Food and Drug Administration for this indication. At present, no guidelines support the choice of one agent over another. Although several drug interventions have been employed for this problem, megestrol acetate and mirtazapine are becoming increasingly used for appetite stimulation. These drugs represent two feasible options for geriatric patients because of their generally favorable adverse‐effect profiles and few drug interactions, but they are often misused. In a comprehensive search of the MEDLINE and International Pharmaceutical Abstracts databases, we identified all published reports on the use of megestrol acetate or mirtazapine for the treatment of weight loss and on any adverse events associated with these drugs. Special emphasis was placed on trials performed in an elderly population. Results were conflicting, most likely because of differing study designs and small numbers of patients. Megestrol acetate and mirtazapine appear to be effective for appetite stimulation and weight gain in some settings. However, applicability of the data to elderly individuals is unclear, and adverse events reported in a few of the trials and in case reports were not benign. Therefore, the use of megestrol acetate or mirtazapine for weight loss should be thoroughly evaluated on an individual basis. Pharmacotherapy should be used only after all underlying causes of weight loss are assessed and treated.

Adverse Reaction to a Dietary Supplement in an Elderly Patient

OBJECTIVE To describe the case of an elderly patient who experienced hepatic enzyme elevations and symptoms of hepatitis associated with the administration of a dietary supplement. CASE SUMMARY A 92-year-old white woman with no history of hepatic disease developed jaundice and increased confusion associated with increased hepatic enzymes. The hepatitis panel, abdominal ultrasound, and antinuclear antibody screen indicated no abnormalities. A drug regimen review revealed that the patient was receiving a dietary supplement, Nutrilite Double X Multivitamin–Multimineral. Following discontinuation of the supplement, the patients symptoms resolved and the hepatic enzymes decreased or returned to the reference range at evaluations occurring 1 week and 1 month after intervention. An objective causality assessment revealed this to be a probable adverse drug event. DISCUSSION While the association of certain herbal preparations with hepatotoxicity has been demonstrated, the potential for this adverse effect is easily overlooked. In this patient, infectious or autoimmune causes of acute hepatitis were ruled out, and drug-induced causes were considered. The resolution of symptoms and laboratory values following discontinuation of the supplement support a relationship between the dietary supplement and this episode of hepatitis. CONCLUSIONS Our case indicates that there was a probable relationship between the dietary supplement Nutrilite Double X Multivitamin–Multimineral and the development of acute hepatitis. Due to the multiingredient formulation of the product, as well as lack of data describing manufacturing procedures, it is difficult to determine which component may be associated with this effect. Over-the-counter supplements should be considered as a part of the differential diagnosis in patients presenting with increased liver enzymes and related symptoms.

Antipsychotic Dose-Sparing Effect with Addition of Memantine

OBJECTIVE: To describe a case of an antipsychotic-sparing effect achieved after the addition of memantine to the regimen of a patient with severe Alzheimers disease and aggressive behavioral disturbances. CASE SUMMARY: A 78-year-old white man with severe Alzheimers disease was receiving risperidone 2 mg 3 times daily for persistent aggressive and dangerous behavioral disturbances. Memantine was initiated, and the dose was titrated to 10 mg twice daily. The patients response included improvement in functional status and resolution of problematic behaviors, allowing repeated reduction of the risperidone dose and ultimate discontinuation. DISCUSSION: Antipsychotics are often employed to treat behavioral disturbances for patients with Alzheimers disease; however, the adverse effect potential of these agents remains a significant concern. Adjunctive medications that maintain or improve behavioral symptoms yet allow an antipsychotic-sparing effect are attractive. Such experiences have previously been described with other drug classes, but clinical experience is evolving with memantine. For this patient, the effect of this agent on behavioral symptoms and risperidone requirements is one example of such an antipsychotic-sparing effect. CONCLUSIONS: Response to memantine therapy may include behavioral improvements allowing a dose-sparing effect of antipsychotic medication. Changes in psychoactive drug burden may be a valuable surrogate marker of memantines effects on behavior.

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 patients 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.

Mind Your P's and Q's: Transcription Errors and Elderly Patients:

TO THE EDITOR: With the recent intensified focus on medication errors, the play on words in this letter is intended to highlight the importance of accurate transcription of drug regimen details. Two inadvertent overdoses of levothyroxine in elderly patients are described, one a tenfold overdose as a result of a misplaced decimal point (P) and the other a twofold overdose as a result of a mis-transcribed interval, qd instead of qod (Q). Case Reports. The first scenario involves an 82-year-old male nursing facility resident with Alzheimer’s disease and hypothyroidism. While receiving 25 mcg levothyroxine daily, his thyroid-stimulating hormone (TSH) level was 0.25 μU/mL (thyroxine not reported) and an order was handwritten to “decrease levothyroxine to 20 mg daily.” Due to a poorly legible designation of mg vs μg, this was transcribed as .20 mg and subsequently supplied as 200 mcg, resulting in a tenfold increase in the intended dose. The patient received the new dose for 6 days. No overt symptoms of hyperthyroidism were observed, although a repeat TSH test revealed an undetectable level. The TSH normalized after discontinuation of the medication. The second scenario involves a 96-year-old female resident of a skilled nursing facility. Although hypothyroidism was not among her admission diagnoses, levothyroxine 0.175 mg qd was among the admission medications. Review of hospital discharge records revealed a previous dose of 0.175 mg qod (every other day). Laboratory work revealed a TSH level of 0.14 μU/mL. Facility staff described the patient as anxious and agitated with a poor appetite, for which olanzapine and cyproheptadine were also prescribed. The levothyroxine dose was reduced, and the TSH normalized one month later. As the woman’s mood and appetite improved, recommendations to reduce the olanzapine and cyproheptadine doses resulted in discontinuation of cyproheptadine. Discussion. These cases illustrate the need for vigilance when transcribing medication orders, particularly when transferring patients between healthcare environments, when old records may be required to provide baseline information about drug therapy. Interdisciplinary review can identify inaccuracies and potentially prevent or resolve medication errors and related adverse effects. Such reviews may also help to eliminate a “prescribing cascade,” based on which new medication is prescribed to alleviate the adverse effects of an existing medication. Several published reports and guidelines describe strategies healthcare systems can implement to prevent or reduce errors.1-3 However, it remains relevant to report individual cases that highlight specific medications that may be particularly error prone. Levothyroxine may be associated with several commonly cited problematic aspects of prescription writing.3 In the first case, 20 mcg was transcribed as 20 mg, and subsequently transcribed again as .20 mg without a leading zero. In the second case, the Latin abbreviation qod was transcribed as qd. Levothyroxine is not included in the Institute for Safe Medication Practices’ list of high-alert medications.3 It is not among the medications commonly cited in list criteria as potentially problematic in elderly patients,4 and hormone and hormone antagonists represent only 2.5% of adult toxic exposures and 0.062% of fatalities.5 However, it nonetheless has the potential to be harmful if administered incorrectly. Elderly patients are particularly vulnerable to adverse drug events, and even medications generally considered benign may be problematic when erroneously transcribed. Rebecca B Sleeper PharmD FASCP BCPS Assistant Professor, Geriatrics Department of Pharmacy Practice School of Pharmacy Health Science Center Texas Tech University 3601 4th Street, Suite 1C162, Mail Stop 8162 Lubbock, Texas 79430-8162 fax 806/743-4209 rebecca.sleeper@ttuhsc.edu

Using a Polypharmacy Simulation Exercise to Increase Empathy in Pharmacy Students

Objective. To assess whether the Jellybean Polypharmacy Simulation Exercise (JPSE) improved empathy in pharmacy students. Methods. The JPSE was given to all third-professional year pharmacy students in a required Special Populations course with pre- and post-scores on the Kiersma-Chen Empathy Scale (KCES) assessed, and open-ended questions on lessons learned from the exercise. Results. Pharmacy students showed a statistically significant increase in KCES scores after completing the JPSE. Open-ended question responses reflected personal growth and appreciation for patients managing difficult medication regimens. Conclusion. This polypharmacy simulation showed the ability to increase empathy in pharmacy students, as well as mimic a realistic experience in managing a multi-drug, multi-dose medication regimen.