Cognitive dysfunction is a core symptom of depression that tends to persist even after treatment and improvements in mood. A study published December 13, 2016, in Biological Psychiatry suggests that modafinil—a wake-promoting agent approved to treat patients with narcolepsy—might be able to help patients with remitted depression who are experiencing cognitive deficits.

Katherine Burdick, Ph.D., says that before health care professionals start prescribing modafinil for persistent cognitive dysfunction to patients with remitted depression, more studies must evaluate the long-term effectiveness and safety of the drug.

“This study points toward an often-overlooked problem in treating depression, which is the assumption that once the depressive symptoms remit, our clinical job is done,” said Katherine Burdick, Ph.D., a professor of psychiatry and neuroscience at the Icahn School of Medicine at Mount Sinai, who was not involved with the study. “In reality, a fair number of patients [with remitted depression] will suffer from persistent difficulties in attention and memory functions. These problems need to be addressed,” she told Psychiatric News.

Past studies have highlighted the cognitive-enhancing effects of modafinil in patients with schizophrenia and attention-deficit/hyperactivity disorder as well as healthy controls, but few have looked at the potential of the medication to treat cognitive deficits in patients with remitted depression.

For the current study, Barbara Sahakian, Ph.D., of the University of Cambridge and colleagues recruited patients in remission from depression (score of less than 12 on the Montgomery-Asberg Depression Rating Scale for at least two months). A total of 60 patients (48 were taking antidepressants) were evaluated using the Cambridge Neuropsychological Test Automated Battery, which includes tests of episodic memory, working memory, planning, and attention. One week after the baseline evaluation of cognitive function, the patients were randomized to receive either a single dose of modafinil (200 mg) or placebo, followed by another round of cognitive tests two hours later.

The researchers found that the modafinil group significantly outperformed the placebo group on episodic memory and working memory tests. There was no significant difference between the groups on planning and attention tests.

Although none of the study participants reported significant adverse events during the testing or 24 hours after the study, two patients taking modafinil reported sleep disturbances on the night of the study session.

“To our knowledge, this study is the first to investigate the effects of modafinil in remitted depression,” wrote Sahakian and colleagues.

“People with persistent cognitive symptoms often experience poorer outcomes such as impaired work functioning and are at increased risk for relapse,” Sahakian told Psychiatric News. “Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.”

Both Sahakian and Burdick noted limitations in the study’s design, such as investigating only the acute effects of modafinil. Sahakian mentioned that longer-term studies with modafinil are needed to determine the drug’s direct impact on quality of life. Burdick, who is currently studying modafinil in patients with bipolar disorder, was concerned about long-term safety.

“Safety will be an additional important focus, as modafinil appears to be safe in single-dose studies, but little is known about what happens if a person takes it daily over the course of a longer period,” said Burdick.

The study was funded by the Medical Research Council and the Wellcome Trust. ■