Is Modafinil a ‘Smart’ Choice to Treat Cognitive Problems in Psychiatric Disorders?

Modafinil was developed to promote wakefulness in people with narcolepsy and other sleep disorders, but the stimulant’s reported ability to improve thinking and memory has led to its off-label use as a “smart drug” by people without sleep problems.

Banner Health/Mount Sinai School of Medicine

Despite modafinil’s popularity as a cognitive enhancer, there has been little conclusive evidence on the extent and nature of the cognitive effects of the medication in healthy people. A meta-analysis published last month in the journal European Neuropsychopharmacology suggests that modafinil does indeed confer some cognitive benefits in non-sleep deprived individuals.

The analysis revealed that people who took modafinil had greater improvements in certain areas of executive function, primarily decision making and planning. Moreover, modafinil was also well-tolerated.

There are still medical concerns with this stimulant (such as potential addictive properties), which coupled with ethical considerations (modafinil could be seen as a performance enhancer) would suggest that it is premature to consider modafinil as a brain booster among the general public.

Modafinil may be able to improve cognitive performance in patients with neuropsychiatric disorders, but few trials have assessed the medication in this patient population.

For example, patients with Alzheimer’s disease or other dementias might benefit greatly from modafinil, Anna Burke, M.D., a geriatric psychiatrist at Banner Alzheimer’s Institute in Phoenix, told Psychiatric News.

“About 70 percent of Alzheimer’s patients will develop apathy, and that severely impacts cognitive decline, particularly executive function and ability to plan,” Burke said. “And often physicians will mistake apathy for depression and prescribe an antidepressant, which only makes the patient more withdrawn and disengaged.”

According to Burke, many of the modafinil studies carried out in healthy participants found that the medication could boost energy, and participants reported less fatigue and better reaction time. A similar effect in people with dementia might help to improve social function and, by extension, brain health, Burke said.

Some physicians have been prescribing modafinil for that purpose, though so far there is scant evidence for how effective it might be besides individual case reports. One small clinical study (23 patients) in 2012 found no evidence that modafinil lowered apathy, while a 2013 trial in Italy (7 patients) suggested the drug was associated with improvements in attention and cognitive state. Two recent clinical trials have shown that methylphenidate—another stimulant—might improve attention and apathy among Alzheimer’s patients, which provides some rationale that modafinil would have beneficial properties as well. “And we would expect modafinil to have fewer side effects than methylphenidate or some other stimulating agents in these patients, so I think it would be worth pursuing further clinically,” Burke said.

Modafinil has shown some promise as a treatment for patients with bipolar depression, though primarily to assist with the sleep problems that are core components of this disorder. There are data suggesting that modafinil is an effective adjunct to help with depressive symptoms in people with bipolar disorder, but now some researchers are beginning to explore modafinil’s cognitive effects in these patients as well.

“Most people didn’t really think cognitive defects were a significant problem in bipolar disorder, so targeting them wasn’t considered a goal of clinical studies,” said Katherine Burdick, Ph.D., an associate professor of psychiatry and neuroscience at Mount Sinai School of Medicine.

Burdick noted that one reason these deficits may have gone unrecognized is that the cognitive effects of bipolar disorder have great heterogeneity, with many people being able to function at very high levels while others have problems performing basic cognitive tasks.

Sleep disturbances are likely a factor that contributes to cognitive difficulties, and prescribed sleep medications like benzodiazepines have cognitive side effects that only exacerbate problems. Also, oftentimes insomnia associated with bipolar disorder is the result of a shift in circadian biology, leading to patients’ staying up late at night while they lack energy and drive during the day.

Burdick is undertaking a clinical study to see whether modafinil can improve this imbalance in circadian rhythm and whether a morning dose can improve cognition and sleep schedules.

“Dosing in the morning is important because we do not want to induce sleep deprivation, which has been shown to increase risks of inducing mania or psychosis,” Burdick told Psychiatric News.

Burdick said she is hopeful that her work in this area may lead to increased interest in the connection between bipolar depression, sleep disorders, and cognition. ■