Treating the Cognitive Symptoms of Schizophrenia

Leslie Citrome, MD, MPH


October 24, 2013

Adjunctive Pharmacotherapy for Cognitive Deficits in Schizophrenia: Meta-analytical Investigation of Efficacy

Choi KH, Wykes T, Kurtz MM
Br J Psychiatry. 2013;203:172-178

Study Summary

Choi, Wykes, and Kurtz examined the comparative efficacy of adjunctive medications on cognition and other symptoms in patients with schizophrenia. They identified 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic, or serotonergic receptor classes. Cholinergic medications (agonists such as donepezil, galantamine, and rivastigmine) produced marginal improvement in verbal learning and memory and moderate improvements in spatial learning and memory. Cholinergic and glutamatergic agents (agonists such as D-cycloserine, D-serine, and CX516) produced moderate effect-size improvements in negative symptoms and small effect-size improvements in general symptoms. Serotonergic agents (agonists such as buspirone, tandospirone, tropisetron, and mianserin) produced small effect-size improvements in positive symptoms.


At present, no agents are approved by the US Food and Drug Administration (as adjunctive medications for the treatment of schizophrenia; however, this is an active area of commercial drug development. The results so far, as shown in this meta-analysis, are minimal to modest. Agents undergoing regulatory approval in the United States for the indication of cognitive improvement in schizophrenia require that both cognitive testing and an assessment of functioning be used as co-primary outcomes. These are high hurdles. In contrast, agents undergoing regulatory approval for the indication of negative symptoms in schizophrenia do not require a co-primary outcome of functionality.

In phase 3 of clinical development are adjunctive bitopertin, a glycine transport inhibitor being tested for negative symptoms associated with schizophrenia, and EVP-6124, an alpha-7 nicotinic acetylcholine receptor agonist being tested for its potential procognitive effects. Stay tuned.



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