SEP-363856 does not block dopamine 2 (D2) or serotonin 2A (5-HT2A) receptors in vivo, which are thought to mediate the effects of currently available antipsychotic medicines
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What does this mean?
“SEP-363856 was found to be generally well tolerated with notable similarities to placebo treatment in discontinuation rates; proportion of patients experiencing extrapyramidal symptoms or akathisia (restlessness); and change in metabolic parameters such as weight, lipids, glucose and prolactin.”
Does this imply there are or aren’t extra pyramidal effects of this drug? Or are the EPS the same as the placebo? It doesn’t seem clear with the semi colon.
If the placebo has the same effect on eps and weight gain as the AP , it looks like a new wonder drug!
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This is good news. I hope the results of the phase 3 trials are good.
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Yeah that’s what they are saying - similar levels of EPS, akathisia and weight gain, prolactin, lipids, glucose - between the placebo and the drug. This was at 4 weeks, so I would like to see longer term, but so far so good.
As far as the side effects that were greater than placebo:
Authors noted that study completion rates between both groups were similar, with the placebo group retaining 79.2% of patients and SEP-363856 group retaining 78.3%. Adverse events occurring with an incidence of 2% or greater and at a higher rate than placebo include somnolence (6.7% vs. 4.8%), agitation (5.0% vs. 4.8%), nausea (5.0% vs. 3.2%), diarrhea (2.5% vs. 0.8%), and dyspepsia (2.5% vs. 0%).
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i think sep-363856 is alternative to current antipsychotics(with better side effect profile) but it is not for negative symptoms. i think it is impossible to treat both negative and positive symptoms with a drug. positive and negative symptoms opposite
That is if the negatives weren’t caused by the APs in the first place.
most negative effects imo are accentuated by meds, sedation- Apathy, blunt effect- sedation numbing,
idk i forget a lot but i think meds playa huge part in negative symptoms
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They did measure the PANSS negative subscale separately, and there was improvement in the medication group vs placebo. But I don’t know how meaningful this change really is. 3.6 points is better than 1.6 but is it life altering? IDK, maybe? I don’t know how this compares to other medications.
Edit: I still don’t know but apparently MIN-101 had a similar result on the negative subscale of the PANSS, around 3.5 points. Different patient profile though, acute exacerbation vs chronically ill but stable. Also I don’t know the effect size.
Secondary efficacy assessments that compared SEP-363856 versus placebo support the findings of the primary endpoint including change from baseline to Week Four in the Clinical Global Impressions-Severity (CGI-S) score (-1.0 vs. -0.5; p<0.001), PANSS positive subscale score (-5.5 vs. -3.9; p=0.019), PANSS negative subscale score (-3.1 vs. -1.6; p=0.008), PANSS general psychopathology subscale score (-9.0 vs. -4.7; p<0.001).
This drug and Karxt are the drugs Im keeping an eye on.