August 2007

Lithium and the Risk of Alzheimer's
Lithium treatment may decrease the risk of Alzheimer's disease in patients with bipolar disorder.

T3 Augments SSRI Treatment
Adding triiodothyronine (T3) to sertraline (Zoloft and others) treatment increased response and remission rates in depressed patients.

Adding Atomoxetine to an SSRI: A Negative Study
Adding atomoxetine (Strattera) to sertraline (Zoloft and others) did not increase remission rates for depressed patients who responded incompletely to the antidepressant alone.

A Tale of Two Interactions
Quetiapine (Seroquel and others) can raise levels of r-methadone, and carbamazepine (Tegretol and others) can lower levels of aripiprazole (Abilify).

Risperidone and Prolactin in Young Patients
Prolactin levels increased in children and adolescents treated with risperidone (Risperdal) for pervasive development disorder.

In Brief
Topiramate and Cognitive Impairment in Children; Brain Structure Abnormalities in Pedophiles

More on Antidepressants and Suicide
A meta-analysis of studies of children and adolescents with depression, obsessive compulsive disorder, or anxiety disorders found a small increased risk of suicidal ideation/suicide attempt, but no completed suicides.

Lithium and the Risk of Alzheimer's

August 2007

Bipolar disorder is associated with an increased risk for dementia.1 At therapeutic concentrations, lithium, one of the main treatments for bipolar disorder, inhibits glycogen synthase kinase-3, an enzyme involved in the metabolism of amyloid precursor protein and the phosphorylation of tau protein. Both of these are integral in the formation of neuritic plaques and neurofibrillary tangles, which are pathognomonic of Alzheimer's disease. Nunes and others in Brazil investigated whether lithium might attenuate the risk of elderly patients with bipolar disorder developing Alzheimer's disease.1

Recruiting patients at their medical school, investigators identified 118 with bipolar disorder who were at least 60 years old. These 37 men and 81 women had an average age of 68.2 ± 5 years. Fifty-nine percent had normal cognitive function; 21%, mild cognitive impairment; and 19%, dementia. (In an age-matched population, the expected rate of dementia would be only 7%—underscoring the heightened prevalence of dementia in patients with bipolar disorder.) Of 23 patients with dementia, 19 were diagnosed with Alzheimer's disease.

For their analysis, the authors divided the patients into two groups. Sixty-six patients had been on continuous treatment with lithium for a mean of 71.2 ± 71.7 months. Another 48 patients had been treated with other mood-stabilizing drugs for at least the past 6 months. Strikingly, the prevalence of Alzheimer's disease was 5% in the group on continuous lithium treatment (3 of 66 patients) versus 33% (16 of 48 patients) in those without recent lithium therapy (P < .001).

The sample is small and naturalistic, but it was a hypothesis-driven study and is indeed intriguing. This finding merits follow-up as the population ages and the number of people suffering from Alzheimer's is expected to explode over the coming decade.

1Nunes PV, Forlenza OV, Gattaz WF: Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder. Br J Psychiatry 2007;190:359-360.