The negative symptoms of schizophrenia are an unmet treatment target as currently approved treatments mostly control positive symptoms. The persistence of these symptoms holds back the patient's reinstatement in society, making them incapable of fulfilling their social, professional, or family roles. There is overwhelming research evidence suggesting that the negative symptoms of schizophrenia are associated with poorer functioning and lower quality of life than positive symptoms, confirming the need for developing new treatments for this particular category of symptoms. This present review aims to review clinical trials addressing novel pharmacological approaches addressing primary negative symptoms of schizophrenia. We overview both monotherapies, first-generation and second-generation antipsychotics, and add-on therapies, including psychostimulants, anti-inflammatory drugs, antidepressants, molecules targeting glutamatergic, cholinergic or serotonergic systems and hormones. Our findings suggest that the primary negative symptoms of schizophrenia may be mitigated by adjunctive therapies, and we highlight the pharmacological agents that have proven superior efficacy. Novel compounds such as cariprazine and MIN-101, to date, show promising results, but large clinical trials are needed to test their efficacy and safety.
Keywords: antipsychotic add-on therapies; deficit syndrome; pharmacological treatment; primary negative symptoms; schizophrenia.
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