Dear Dr. Aiken: The article on Trintellix and cognition (TCPR, February 2019) reminded me of another industry claim: that atypical antipsychotics improve cognition. Any truth to that one?

Dr. Aiken: I’ve also heard this whispering campaign, and there is reason to doubt it. The logic goes like this: Unlike the typical antipsychotics, atypicals improve both cognitive and psychotic symptoms of schizophrenia, so they must have procognitive effects of their own that can be harnessed in mood disorders, ADHD, and even dementia. The problem is that the data show the opposite.

Atypicals tend to worsen cognition in mood disorders, and the problem is more pronounced as the dose goes up. Most of this research was done in bipolar disorder, where atypicals came out behind on cognitive measures in head-to-head comparisons with anticonvulsants and lithium (Daglas R et al, Eur Psych 2016;31:20–28; Cankorur V et al, Noro Psikiyatr Ars 2017;54:244–250). Lurasidone (Latuda) may be an exception. This atypical actually improved cognition independently of mood in stable bipolar I patients with cognitive problems in a 6-week, randomized, open-label, industry-funded trial (dose 20–80 mg/day) (Yatham L et al, Lancet Psych 2017;4(3):208–217).

One antipsychotic, aripiprazole (Abilify), is rumored to have specific benefits in ADHD through its unique partial dopamine agonism. This theory has been discredited, but not completely quieted, by two negative randomized controlled trials (Ghanizadeh A et al, Neurosciences 2013;18(4):323–329).

The cognitive benefits of atypicals don’t translate from schizophrenia to other disorders, but how well do they hold up in schizophrenia? Cognition definitely improves when schizophrenia is treated with atypicals, but that improvement appears due to the resolution of psychosis rather than direct cognitive effects of the atypicals. Early studies did find superior cognitive outcomes when atypicals were compared to typical antipsychotics, but that research was stacked in favor of the newer drugs (for example, the typical antipsychotics were dosed higher and often used with anticholinergics). In the larger, NIH-funded CATIE trial, cognition improved equally well with either class. On the other hand, there are concerns that atypicals may impair cognition over the long term, such as through their effects on metabolism, frontal lobe functioning, or cholinergic transmission (MacKenzie NE et al, Front Psych 2018;9:622).

There are many reasons to use atypicals, but cognition is not one of them. When a patient complains of feeling cloudy headed on an atypical antipsychotic, consider a lower dose, particularly if the patient has a mood disorder.