Is lumateperone effective for negative symptoms?

is lumateperone effective for negative symptoms?

and they say novel for lumateperone but there are 5-HT2A receptor antagonist and D1 receptor antagonist. how is lumateperone novel??

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I’m afraid it’s going to turn out to be another dud antipsychotic.

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Novel is a vague term. It is novel in that it has such low dopamine D-2 occupancy compared with previous meds.

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We wont know until it is able to be used for the general population. Like @robertc said it is a partial agonist at the D2 receptor site like abilify, vraylar and rexulti, but to a greater extent as well as D4. I think this could huge for negative symptoms which might worsen on some APs due to less dopamine in certain receptors, but D1 is the main culprit (as far as we know) for sz

But still, Ill believe it when I see it

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so there is not so much change…

Promising but still in stage III trials. Still have a ways until we know if it will work effectively for negative symptoms.

Intracellular says it helps some negative symptoms.

Specifically related to social function.

The data presented at ASCP included analyses from our schizophrenia studies (‘301 and ‘005) showing that lumateperone selectively improves this critical negative symptom domain of emotional experience compared to placebo. Importantly, these results are consistent with previous data that demonstrated improved social function with lumateperone as measured by the Personal and Social Performance Scale.

It does target many of the old familiar neurotransmitter systems, but also ones not (apparently) covered by current meds.

Lumateperone is a potent 5-HT2A antagonist, a mesolimbic/mesocortical dopamine phosphoprotein modulator (DPPM) with pre-synaptic partial agonist and post-synaptic antagonist activity at D2, a glutamate GluN2B receptor phosphoprotein modulator with D1-dependent enhancement of both NMDA and AMPA currents via the mTOR protein pathway and an inhibitor of serotonin reuptake.

Probably the most important new feature though is that it had a safety profile similar to placebo, with no cardiometabolic or movement side effects.

Of course it’s going to work for some people and not others. After all, not even clozapine works for everyone.

It has finished phase 3 and word is expected from the FDA by the end of August or so.

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if it does target many of the old familiar receptors, should it have similiar side effects?

Its affect on dopamine D-2 is much smaller than any previous antipsychotic. That may be why the side effects are much smaller for most patients.

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Sleepiness is apparently the most common side effect. But I believe this has a once a day dosing so it could be taken at night.

Somnolence was the most common drug-related adverse event, occurring in 6.6% of the lumateperone cohort.
No drug-related serious adverse events occurred, according to researchers.
Akathisia occurred in 0.3% of participants and extrapyramidal side effects occurred in 0.7%.

I believe that’s well below other commonly used antipsychotics. There was another study with the larger, 120 mg dose where 32% of the participants reported the sleepiness side effect. Likely dose related.

A responder analysis of participants who were presumed symptomatically stable indicated more than 20% of participants exhibited at least a 20% improvement in PANSS total scores.
Researchers found significant improvements in positive symptom subscale scores ( P < .001), general psychopathology subscale scores ( P = .014), PANSS-derived prosocial factor scores ( P < .001), and social functioning as measured by the Personal and Social Performance scale ( P < .001).
Among a subgroup of participants (n = 36) with prominent negative symptoms at baseline, negative symptom subscale ( P = .029) and the Marder Negative Factor ( P = .014) also significantly improved.

From baseline to treatment end, body weight ( P = .001), BMI ( P = .001) and waist circumference ( P = .005) decreased.

From baseline to day 42, total cholesterol ( P = .002), LDL cholesterol ( P = .001), triglycerides ( P = .035) and prolactin ( P = .001) significantly decreased.

Multi-positional blood pressure or heart rate did not change after lumateperone treatment, and there were no reported cases of orthostasis and QTc interval prolongation

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