Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia.

Abstract

Current treatments for schizophrenia function by blocking neurotransmission at dopamine D2 receptors. These compounds have proven highly effective for treatment of schizophrenia and especially for management of positive symptoms. A range of compounds and formulations are presently available, which permits tailoring of side effects to optimize treatment for individual subjects. Nevertheless, many patients suffer from persistent negative symptoms and neurocognitive deficits that contribute to persistent psychosocial impairments and long-term disability. At present, there are no approved pharmacological treatments for either negative symptoms or neurocognitive dysfunction. Instead, various behavioral approaches such as diet, exercise and cognitive remediation may be needed to help optimize cognitive function and mitigate symptoms. Furthermore, neuromodulation approaches, such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) are beginning to be employed both to minimize symptoms and to augment cognitive retraining approaches. At present, encouraging effects of tDCS on persistent auditory hallucinations have been reported, and if confirmed, may open the way for more widespread use of non-pharmacological treatments. At present, phase III studies remain ongoing for α7 nicotinic agonists in treatment of cognitive impairments and glycine reuptake inhibitors for suboptimal treatment response. Furthermore, preclinical studies suggest that glutamate-based treatment approaches may be effective if applied early in the illness. Future studies are needed to determine whether this will lead to effective approaches to halt illness progression for individuals at high clinical risk for schizophrenia.