New. Min-101 helps negatives in trials. But positives?

Min 101shows to help with schizophrenia negatives, but not so much with positives. But they say that they can adjust min101 to hopefully target positive symptoms.

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Need a login to view the article.

That’s funny, I don’t think I need to log in.
If anyone can quote the article that’ll be good.

It’s basically saying that min101 is very good for negatives, but not really positives, or something like that.

MIN-101, an investigational antipsychotic, appears to be safe and effective for the treatment of negative symptoms of schizophrenia, new research shows.
Investigators led by Michael Davidson, MD, professor of psychiatry, Sackler School of Medicine, Tel Aviv University, Israel, compared two different doses of MIN-101 (32 mg/day and 64 mg/day) to placebo in patients with schizophrenia.
At 12 weeks, they found a statistically significant difference in negative factor score on the Positive and Negative Syndrome Scale (PANSS), with lower scores for the MIN-101 groups compared with the placebo group. Similar improvements were seen in scores on Other measures of negative symptoms, including the Brief Negative Symptom Scale.
“For the majority of schizophrenia patients, negative symptoms persist long after positive symptoms improve or remit and are responsible for the poor social and vocational abilities of these individuals,” Dr Davidson told Medscape Medical News.
“For the first time, there is a real possibility that a drug could ameliorate negative symptoms without the adverse effects of the currently available drugs used to treat schizophrenia,” he said.
The study was published online July 28 in the American Journal of Psychiatry.
Alternative to Dopaminergic Agents

“Currently available antipsychotic drugs, all of which to varying degrees have antidopaminergic activity, ameliorate positive symptoms in about two-thirds of acutely ill patients,” but do not sufficiently address negative symptoms, the authors write.
Although amisulpride, asenapine, and cariprazine have been regarded as beneficial for negative symptoms, “their specificity and advantages in this regard remain debatable.” Moreover, some dopamine D2 receptor blocking agents produce secondary negative symptoms.
MIN-101 is a novel cyclic amide derivative that has high equipotent affinities for sigma-2 and 5-hydroxytryptamine2A (5-HT2A) receptors but has no direct dopamine affinities.
The authors hypothesize that sigma-2 receptors may be involved in counteracting dysregulations in key dopamine and glutamate neurotransmitter pathways. Moreover, "5-HT2A receptors may be implicated in schizophrenia, hence blocking these receptors may contribute to MIN-101’s therapeutic effect."
A previous phase 2a randomized, placebo-controlled study of patients with acute schizophrenia found that MIN-101 yielded statistically significant improvements in negative symptoms, as compared to placebo.
The current phase 2b trial “was designed to confirm and extend the findings of the phase 2a trial in symptomatically stable schizophrenia patients,” the authors state.
“While benefiting positive symptoms, currently available antipsychotic drugs possess effects which are very similar to negative symptoms, and as such, no FDA-approved drug targeting negative symptoms exists, making the development of drugs for negative symptoms an unmet need and a research priority,” Dr Davidson said.
Spurious Findings Unlikely

To investigate the efficacy, safety, and tolerability of MIN-101 in patients with schizophrenia who have negative symptoms, the researchers studied 244 patients (aged 18-60 years) who were symptomatically stable and had had negative symptoms for less than 3 months prior to entering the trial.
Patients were required at baseline to have at least “moderately severe” negative symptoms, defined as a score of ≥20 on the “classic” seven-item negative symptom scaled of the PANSS (items N1 - N7). In addition, they were required to have scored <4 on six PANSS items (excitement, hyperactivity, hostility, suspiciousness, uncooperativeness, and poor impulse control).
Patients with arrhythmias, such as long QT syndrome, were excluded. Also excluded were patients who had been diagnosed with another mental disorder, had experienced suicidality, had an unstable medical disorder, or had engaged in substance abuse within 3 months of the screening.
Patients underwent a washout period prior to the study onset. Those being treated with depot antipsychotics were withdrawn from their treatment for at least 1 month, were hospitalized, and were then withdrawn from all psychotropic drugs for at least 5 days prior to randomization. Close to 70% of patients had been treated with oral second-generation antipsychotics prior to entering the trial.
No psychotropic drugs other than MIN-101 were allowed during the trial. However, patients were allowed to take rescue medications for insomnia or agitation. Anticholinergic agents were also discontinued at baseline but were allowed for patients who experienced emergent extrapyramidal symptoms (EPS).
Patients were randomly assigned in a 1:1:1 ratio to receive either placebo or oral MIN-101 (32 mg/day or 64 mg/day) for 12 weeks. The researchers assessed efficacy and safety at baseline before the first dose of medication, at weeks 2, 4, 8, and 12, or on premature termination. Outpatients were contacted by telephone or at weeks 6 and 10 to ascertain safety and adherence to the study medication.
The researchers selected the negative factor score of the PANSS from the pentagonal structure model as the primary outcome measure (items N1 - N4, G5 - G8, G13, G14).
Secondary outcome measures were the PANSS total score, PANSS positive, negative, and general psychopathology scale scores, the individual pentagonal factors of the PANSS, the Brief Negative Symptom Scale score, CGI severity and improvement scores, Brief Assessment of Cognition in Schizophrenia (BACS) score, and Calgary Depression Scale for Schizophrenia (CDSS) score. The Abnormal Involuntary Movement Scale (AIMS) was used to evaluate EPS.
At the end of 12 weeks, the researchers found a statistically significant reduction in the primary endpoint — ie, the PANSS negative symptom pentagonal structure factor score for the MIN-101 32 mg/day and 64 mg/day groups, as compared with the placebo group (P ≤ .024, d = 0.45; and P ≤ .004, d = 0.57, respectively).
The MIN-101 32 mg/day group showed statistically significant improvements at 2 weeks, and both MIN-101 dosage groups at showed statistically significant improvement at 8 weeks. Benefit was maintained throughout the 12-week period. Similar findings were obtained in the PANSS negative “classic” (N1 - N7) scale and the PANSS total score.
The researchers conducted a per-protocol analysis of the primary outcome measure and found a statistically significant reduction for the MIN-101 32 mg/day group and the 64 mg/day group, compared with the placebo group.

So it’s only been tested as a stand-alone ap, not as an add-on?


I think so.

Yes it’s being tested as a stand alone for people with low positive symptoms who are stable. And they didn’t get any worse as far as positive symptoms over the study period.

They haven’t said anything about it, but it wouldn’t surprise me if eventually it gets used as an add on, the way that some doctors now combine APs to try to get the best effects for their patients. But they are not testing it as an add on.

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I was kinda hoping min101 would be mono therapy, but as an add-on I’m fine with that.

Honestly I’m disappointed in these new drugs in the pipeline.
Nothing stands out for me.

I take it back.
This drug has grabbed my attention.

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Hi @Wave.

That new drug ENLIGHTEN sounds good. I like the name too…ENLIGHTEN.

Hope it’s good antipsychotic. :slight_smile:

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So far it looks promising.