Novel Compound Shows Promise in Treating Negative Symptoms of Schizophrenia

MIN-101—a novel compound that binds to sigma-2 and 5-HT2A receptors—appears to reduce negative symptoms of schizophrenia without major side effects, according to a study in AJP in Advance. Unlike current antipsychotics, MIN-101 has no direct activity on dopamine receptors. 

While most current antipsychotics are effective at treating the positive symptoms of the disorder (such as hallucinations and delusions), targeting the negative symptoms (such as anhedonia) has proven more difficult.

To compare the safety and effectiveness of MIN-101 with placebo, Michael Davidson, M.D., of Minerva Neurosciences and colleagues recruited 244 patients with schizophrenia who had been symptomatically stable for at least three months and had scores of at least 20 on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). After at least five days of withdrawal from all antipsychotic medication, the patients were randomly assigned to receive placebo or MIN-101 daily (either at 32 mg/day or 64 mg/day) for 12 weeks. 

After 12 weeks, the patients taking MIN-101 showed statistically significant improvements in their PANSS negative symptom scores (effect sizes of 0.45 and 0.57 for the low and high doses, respectively [indicating a moderate effect]), but no differences in their positive symptom scores or their Abnormal Involuntary Movement Scale (AIMS) scores. Additionally, no clinically significant changes were observed in vital signs, weight, and metabolic indices, the authors reported. 

“A relevant clinical question is whether the improvement in negative symptoms reported here is specific and clinically meaningful. Indeed, it is possible that MIN-101 has a beneficial effect on mood. However, the effect on negative symptoms was maintained after controlling for depression, which suggests the effect was not synonymous with improvement in mood,” Davidson and colleagues wrote. 

“Furthermore, in the present trial, there was no significant improvement in positive symptoms. Similarly, the AIMS scores were low at baseline and showed only small variations throughout the trial. Hence, the improvement in negative symptoms cannot be attributed to improvements in extrapyramidal symptoms, at least with respect to dyskinetic symptoms.”

This phase 2b clinical trial was funded by Minerva Neurosciences, the developer of MIN-101. The study authors have financial ties to the company.

For related information, see the Psychiatric News PsychoPharm article “Study Suggests Cariprazine May Have Direct Effects on Negative Symptoms.”

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