LZHEIMER DISEASE (AD) IS A neurodegenerative disorder characterized by cognitive decline, impaired performance of activities of daily living, and behavioral and psychiatric signs and symptoms. Pathological features of AD include intraneuronal neurofibrillary tangles containing abnormally phosphorylated tau protein, extracellular amyloid plaques containing the peptide ␤ amyloid, neuronal cell death, and anatomic as well as functional impairment of neurotransmitter systems. 1,2 Alzheimer disease affects approximately 4.5 million people in the United States. 3 Treatments approved by the Food and Drug Administration were previously limited to monotherapy with cholinesterase inhibitors in patients with mild to moderate AD. 2 In October 2003, the Food and Drug Administration approved memantine for the treatment of moderate to severe AD; memantine is now available in more than 40 countries worldwide. Memantine, a low-to moderateaffinity, uncompetitive N-methyl-Daspartate (NMDA) receptor antagonist , represents the first member of a new class of medications showing clinical benefit and good tolerability in AD. Although other NMDA receptor modulators (eg, milacemide and D-cycloserine) have failed in development as Author Affiliations, Financial Disclosures, and Members of the Memantine Study Group are listed at the end of this article.

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Context.-Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression. Objective.-To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease. Design.-Two-week placebo lead-in followed by a double-blind randomized 6week medication trial. Setting.-Research clinics in 4 university centers. Patients.-Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease. Interventions.-Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks. Main Outcome Measures.-For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events. Results.-By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (PϽ.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (PϽ.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (PϽ.03). Conclusions.-Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.

Context.-The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use. Objective.-To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia. Design.-Twelve-week, multicenter, randomized, double-blind trial. Setting.-Thirteen centers across the United States and 1 in Canada.

Antidepressants may not be useful adjunctive therapy for bipolar depressed patients with high serum lithium levels. However, antidepressant therapy may be beneficial for patients who cannot tolerate high serum lithium levels or who have symptoms that are refractory to the antidepressant effects of lithium.