MIN-101, a compound with sigma-2 and 5-HT2A affinities that does not block D₂ receptors, reduced negative symptoms of schizophrenia, according to findings from a study published in The American Journal of Psychiatry.

Previous research has not produced sufficient evidence for a specific pharmacologic treatment for negative symptoms of schizophrenia, and current treatments can exacerbate negative symptoms.

Researchers in this placebo-controlled trial identified 244 symptomatically stable patients with schizophrenia who had scores ≥20 on the Positive and Negative Syndrome Scale negative subscale and score <4 for specific symptoms such as excitement and poor impulse control. Overall positive subscale scores were not limited. Patients diagnosed with additional mental disorders, at high risk for suicide, or with a history of substance abuse were excluded from the study.

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Although investigators noted that ideal patients for this trial would have had severe negative symptoms and mild positive symptoms, such requirements would have excluded a significant proportion of the population. However, they added, the mean Positive and Negative Syndrome Scale negative symptom score of patients was 26.8 (range, 20-38), above the moderate minimum of 20.

Patients were assigned to groups that were prescribed MIN-101 at 32 mg/d, MIN-101 at 64 mg/d, or placebo for 12 weeks.

Patients in the 32 mg/d group saw improvement in negative symptoms at 2 weeks, and both MIN-101 groups saw improvements at 8 weeks. Improvements were maintained throughout the trial. No notable improvement or worsening of positive symptoms occurred over the 12 weeks, and there was no significant change in body weight. Among those taking MIN-101 who reported adverse events (57.7% in the 32 mg/d group and 57.1% in the 64 mg/d group), headache (7.5%) and anxiety (6.8%) were the most common. Others included insomnia, schizophrenia symptoms, asthenia, and nausea.

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The investigators noted that the clinical applicability of MIN-101 is difficult to ascertain while the drug is still in early stages of development. However, they concluded that “MIN-101 demonstrated statistically significant efficacy in reducing negative symptoms and good tolerability in [stable patients with schizophrenia].”

Limitations of the study include its short washout period. Antipsychotic withdrawal could have influenced the improvement in negative symptoms.

Funding: This phase 2b clinical trial was funded by Minerva Neurosciences.

Disclosures: Dr Davidson, Dr Luthringer, and Mr Reilly are employees of Minerva Neurosciences and own stock options in Minerva Neurosciences. Dr Saoud, Dr Staner, Dr Noel, Ms Luthringer, Dr Werner, and Dr Schaffhauser are employees of PPRS Research, a consultant to Minerva Neurosciences; Dr Schaffhauser owns stock in Minerva Neurosciences. Dr Rabinowitz and Dr Weiser are consultants to Minerva Neurosciences.


Davidson M, Saoud J, Staner C, et al. Efficacy and safety of MIN-101: a 12-week randomized, double-blind, placebo-controlled trial of a new drug in development for the treatment of negative symptoms in schizophrenia. Am J Psychiatry. 2017;174(12):1195-1202.