Skip to main content

Second-Generation Antipsychotics Recommended for Negative Symptoms of Schizophrenia

July 01, 2019

A proposed clinical algorithm recommends the antipsychotic cariprazine as the first-line pharmacological treatment for patients with schizophrenia with pronounced negative symptoms. In the event of cariprazine failure, the algorithm advises using the antipsychotic amisulpride.

Researchers published the algorithm in the journal Neuropsychiatric Disease and Treatment.

“Overall, data from the literature suggest that second-generation antipsychotics, such as cariprazine and amisulpride, should be preferred over first-generation antipsychotics, as they are associated with better functional outcomes and lower cognitive impairment,” researchers wrote.

The clinical algorithm was based on current knowledge of negative symptoms of schizophrenia. Studies investigating negative symptoms specifically are scant, however, researchers explained.

Antipsychotic Patch Outperforms Placebo in Phase 3 Trial

“So far, only a few treatments for schizophrenia negative symptoms have been tested, showing only modest results,” they wrote. “The lack of a shared definition of negative symptoms among pharmaceutical regulatory agencies, as well as among researchers, contributes to the inconsistency in inclusion criteria of the existing clinical trials, reducing the chance of drawing solid conclusions.”

Cariprazine demonstrated effectiveness for anhedonia in preclinical models and was more effective than risperidone in patients with schizophrenia with predominant negative symptoms, according to the paper. Meanwhile, amisulpride demonstrated significant efficacy for predominant negative symptoms compared with placebo, although its effect was difficult to disentangle from its effect on depression.

“Further treatment lines may include the use of olanzapine and quetiapine, and add-on therapy with antidepressants,” wrote researchers, who also voiced an urgent need for additional trials and  stronger efforts in drug discovery and development targeting negative symptoms.

—Jolynn Tumolo


Cerveri G, Gesi C, Mencacci C. Pharmacological treatment of negative symptoms in schizophrenia: update and proposal of a clinical algorithm. Neuropsychiatric Disease and Treatment. 2019;15:1525-1535.

Back to Top