November 2009

And a One, and a Two… Exercise for Depression
As an adjunct to medication and psychotherapy or by itself, exercise can be an effective treatment for depression.

Milnacipran (Savella)
Milnacipran (Savella) is the third compound to be approved in the United States for the treatment of fibromyalgia syndrome.

Preventing Depression in Adolescents
Current depression in parents negates the positive effects of a group cognitive behavioral prevention program in preventing depression in adolescents.

Anticholinergic Medicines and Cognitive Decline in the Elderly
Anticholinergic medications can impair cognition and memory, especially in elderly patients.

In Brief
Predictors of Mortality in Depressed Patients following Cardiac Events; Disruption of Dopamine Neurotransmission in ADHD

Raising the SSRI Dose: Does It Help?
Selective serotonin reuptake inhibitors (SSRIs) do not appear to have an obvious relationship of dose to likelihood of benefit.

Generic Antidepressants: Bioequivalent?
Generic formulations of antidepressants may not have the same pharmacokinetics and clinical effects as the original brand-name versions.

Lamotrigine in Borderline Personality Disorder
Preliminary research found lamotrigine (Lamictal) superior to placebo in improving symptoms of affective instability and impulsivity in patients with borderline personality disorder.

Anticholinergic Medicines and Cognitive Decline in the Elderly

November 2009

The world eagerly awaits better treatments to ameliorate and someday prevent symptoms of Alzheimer's and other dementias. In the meantime, the differential diagnosis of a patient with cognitive decline includes a search for treatable causes. Elderly people typically take many medications—prescribed and over-the-counter. A number of these drugs have anticholinergic properties, which can impair cognition and memory and decrease psychomotor speed.

Between 1999 and 2001, Carrière and coauthors conducted a multi-site cohort study in France of community-dwelling people 65 years or older.1 Among other goals, researchers examined the relationship over time between anticholinergic drug use and cognitive decline and the onset of dementia. Participants were 4128 women and 2784 men, whose average age was approximately 74 years. Cognitive performance, clinical diagnosis of dementia, and anticholinergic drug use were evaluated at baseline and 2 and 4 years later.

At baseline, 7.5% of participants reported taking an anticholinergic drug. Women who used anticholinergics at baseline showed greater decline over 4 years in verbal fluency scores and global cognitive functioning compared with women who were not taking anticholinergics. In men, consumption of anticholinergic medicines was associated with a decline in visual memory and, to a lesser extent, executive function. Cognitive decline and the risk of a clinical diagnosis of dementia increased in patients who continuously used anticholinergic drugs but not in those who discontinued them.

There was a significant interaction between anticholinergic intake and apolipoprotein E (APOE) genetic status. Women who were taking anticholinergics and were APOE ɛ4 positive had a twofold higher risk of global cognitive decline (P = .005) than women who took anticholinergics but were APOE ɛ4 negative. This suggests that the presence of the APOE ɛ4 gene confers increased long-term cognitive vulnerability to the effects of anticholinergic medicines in older people—especially in postmenopausal women.

Results from this study reaffirm established clinical wisdom. When faced with cognitive decline in an older patient, seek treatable causes—such as medications that can compromise cognitive function. High on that list should be drugs with anticholinergic properties, including antihistamine products containing diphenhydramine (Benadryl and others). When prescribing or recommending medications for older patients, if possible choose those without anticholinergic properties.

1Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML: Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study. Arch Intern Med 2009;169:1317–1324.