Duloxetine Deemed Safe in Elderly Patients

A team of investigators conducted a meta-analysis of safety data in six studies of duloxetine (Cymbalta) used to treat depression in patients over 55 years old. All six studies were double-blind, placebo-controlled trials and involved 209 patients over 55, 119 who were assigned to duloxetine and 90 who were assigned to placebo. The dose of duloxetine used in these studies ranged from 40 to 120 mg/day. Safety data evaluated included discontinuation rates, changes in vital signs, ECG, blood pressure, laboratory analyses and reports of adverse events. Data from all randomized patients were included in the analysis.

The mean age of patients was 63.91 ± 6.79 years for placebo-treated patients and 61.84 ± 5.89 years for duloxetine-treated patients (p=0.005). The subjects did not differ according to baseline characteristics such as gender, ethnicity or illness history. Adverse events leading to discontinuation that occurred in at least one percent of duloxetine-treated patients and at least twice as often as in placebo-treated patients included dizziness, nausea, erectile dysfunction, somnolence and syncope. However, there were no significant differences between the rates of these adverse events in duloxetine-or placebo-treated patients. Adverse events not which is primarily metabolized by catecho-O-methyltransferase (COMT), whereas monoamine oxidase is primarily responsible for the metabolism of centrally released norepinephrine.

There have been no reports of interaction between MAOIs and epinephrine eye drops in the literature, but a lack of interaction between MAOIs and systemically administered epinephrine was reported in an earlier study with two different MAOIs: phenelzine (Nardil) 15 mg three times daily and tranylcypromine 10 mg three times daily. Both sympathomimetic amines were administered for seven days in the four subjects prior to receiving an epinephrine infusion. No adverse effects on blood pressure or heart rate were recorded.

In conclusion, it appears that epinephrine eye drop can be safely administered to patients who require a MAOI for treatment of refractory depression. However, unless further necessarily leading to discontinuation and occurring in at least five percent of duloxetine-treated patients and significantly more often than in placebo-treated patients included: nausea (p=0.007), dry mouth (p=0.002), constipation (p=0.027), decreased appetite (p=0.039), insomnia (p=0.039), fatigue (p=0.044) and decreased libido (p=0.011). The researchers also found that duloxetine had no clinically relevant effects on blood pressure and did not induce hypertension in this group of patients.

The researchers conclude, "In these studies, duloxetine was found to be well tolerated, and to exhibit a safety profile similar to that of currently available SSRI medications." They add, "Duloxetine exhibited a favorable cardiovascular safety profile, and did not induce hypertension."

Mallinckrodt CH, Kennedy JS, Tran PV, et al.: Duloxetine for the treatment of major depressive disorder in patients age >/=55: a meta-analysis of safety data.

Low-dose Risperidone Treats Delirium in Open Trial

A team of researchers found that low doses of risperidone (Risperdal) improved cognition and symptoms of delirium in an open-label prospective trial. Ten medically ill patients with DSM-IV diagnoses of delirium and Delirium Rating Scale (DRS) scores of at least 13 were administered risperidone, starting at 0.5 mg twice daily. The mean age of the patients was 64.7 years. The presumed medical etiology in these ten patients included: Crohn's disease; lithium toxicity; sepsis; congestive heart failure; chronic obstructive pulmonary dis-ease; hypnotremia/hypokalemia; anemia, deep venous thrombosis and pulmonary infiltrate; anemia, hip fracture and hypoxia; pulmonary effusion and infection; and S/P subdural hematoma evacuation. All patients were receiving various other medications, with an average of 10.4 per patient and ranging from four to 17 concomitant medications.

The patients were treated with risperidone for five days. After the initial dose, patients could be treated with additional doses of risperidone 0.5 mg for behavioral symptoms such as hallucinations, delusions or agitation. The total dose for the first day of treatment was continued until the DRS score was 12 or less, following which the dose was decreased by 50 percent each day. Eight patients completed the study, with one patient withdrawing due to medical complications unrelated to risperidone. Final assessments were made on day three and days four through six for these two patients. The mean dosage on day one was 1.35 ± 0.41 mg/day (range 1 to 2 mg/day) and the mean maintenance dosage was 0.75 ± 0.33 mg/day (range 0.5 to 1.5 mg/day). It took an average of 3.89 days to reach a maintenance dose in these patients and one patient did not reach a maintenance dose.

The researchers found significant clinical difference from day 1 to day 6 on the DRS (p<0.001), the Cognitive Test for Delirium (p<0.001) and the Karnofsky Scale of Performance Status (p=0.008). These improvements occurred without significant changes in the severity of medical illness, as measured by the Cumulative Illness Rating Scale total (CIRS TOT; p=0.872) or severity index (CIRS SI; p=0.213). Additionally, while mild sedation was noted in two patients, there were no extrapyramidal symptoms or changes in QTC interval noted. The researchers conclude that low doses of risperidone were effective in treating delirium in this sample.

Mittal D, Jimerson N, Peoples E, et al.: Treatment of delirium with risperidone: results from an open-label prospective trial.

[New research presented at the Academy of Psychosomatic Medicine Annual Meeting, Tuscon, Arizona, November 2002.]