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Alternative pharmacologic targets for the treatment of schizophrenia: results from phase I and II trials

Purpose of review The current article provides a brief review of the clinical efficacy and safety outcomes from selected phase I and II clinical trials of compounds in development acting on targets beyond the dopamine D2 receptor in patients with schizophrenia. Recent findings A number of experimental pharmacological targets have been studied in clinical trials. Among those, glutamatergic and nicotinergic pathways have received most attention. Glycine transporter 1 inhibitors used adjunctively with antipsychotics suggest efficacy for negative symptoms of schizophrenia. Adjunctive alpha7 nicotinic acetylcholine receptor agonists and minocycline may improve negative symptoms and cognitive deficits. Adjunctive oxytocin may benefit psychotic symptoms and social cognitive deficits. Adjunctive erythropoietin may improve cognitive function. Summary Experimental therapeutic research for schizophrenia is rapidly expanding and a number of compounds with novel mechanisms of action are demonstrating encouraging evidence for efficacy across a range of symptoms. However, much work still needs to be conducted before these new agents can be considered for routine clinical treatment. In particular, further assessment of efficacy and longer term safety and tolerability monitoring are required.