Why so many negative studies? It might be that the best targets have not yet been identified. Alternative agents might include allosteric modulators, reuptake inhibitors, or enzyme inhibitors. Perhaps the problem has been in the choice of dose or dosing schedule, as there are data suggesting that intermittent or once-weekly dosing might better hit the "sweet spot" of drug efficacy, Dr. Buchanan postulated.
Or, it’s possible that drugs require "practice," in the form of cognitive remediation, to be effective. "Rather than continue to search for the miracle drug that will single-handedly reverse the various cognitive impairments, should we be examining the extent to which pharmacological agents can enhance the therapeutic effects of nonpharmacological approaches for the enhancement of cognition?" he asked.
Such interventions might include cognitive remediation such as PositScience (www.positscience.com), cognitive enhancement therapy, cognitive-behavioral therapy (CBT), and even exercise.
In an interview, Dr. Buchanan said that studies are underway using d-cycloserine to enhance CBT and cognitive remediation, and his own group has proposed a study using nicotine to enhance cognitive remediation. Another potential agent that could be used with psychosocial treatment is oxytocin, a naturally occurring hormone, which might facilitate social interactions.
Dr. Buchanan has received grant/research support from Janssen and is a consultant to Abbott Laboratories, GlaxoSmithKline, Sanofi-Aventis, Schering-Plough, and Takeda. He serves on advisory boards for Abbott, Astellas Pharma, AstraZeneca, Cypress Bioscience, Merck, Pfizer, Roche, Solvay Pharmaceuticals, and Wyeth. He also is a data and safety monitoring board member for Cephalon, Otsuka, and Pfizer.