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Posted by revv33 on June 23, 2020, at 5:59:37
Lumateperone is an antipsychotic with 5-ht2a activity and was wondering how does it compare to other antidepressant? Could I get Post-SSRI sexual dysfunction or serotonin syndrome? Or can you not compare both of these antidepressant activity?
Posted by linkadge on June 23, 2020, at 18:07:32
In reply to How does Lumateperone compare to antidepressants?, posted by revv33 on June 23, 2020, at 5:59:37
Lumateperone is a very strong antagonist of 5-ht2a and much less potent as an antagonist at dopamine receptors. As an antipsychotic, it may have fewer dopamine related side effects (i.e. apathy), and as a 5-ht2a antagonist it would be expected to improve sleep, anxiety and perhaps anhedonia (to some degree). Using it alone in unipolar depression, it may behave only weakly as an antidepressant (but it likely depends on the person). It shares the 5-ht2a antagonist effects of drugs like mirtazapine, amitriptyline, and trazodone. If sleep / anxiety were prominent, then it might be more beneficial.
Where it could be particularly useful is either a) as an adjunct to other antidepressants or b) in bipolar depression. Bipolar depression tends to respond differently to antidepressants and oftentimes antipsychotics are better at addressing depression than regular antidepressants. It is not an SSRI (it doesn't increase serotonin by blocking the reuptake mechanism). You could get some sexual dysfunction (owing to the dopamine blockade) but I would think it would be much less likely than with an SSRI. On its own you won't get serotonin syndrome. If it is combined with an SSRI, there is a very very low possibility of some degree of serotonin syndrome. Because the mechanism is quite different to antidepressants, it is not really possible to compare them directly.
Linkadge
Posted by undopaminergic on June 23, 2020, at 21:32:29
In reply to Re: How does Lumateperone compare to antidepressants?, posted by linkadge on June 23, 2020, at 18:07:32
> Lumateperone is a very strong antagonist of 5-ht2a and much less potent as an antagonist at dopamine receptors.
>
> If it is combined with an SSRI, there is a very very low possibility of some degree of serotonin syndrome.
>Why's that? You say it's a very strong serotonin 5-HT2A receptor antagonist, so if anything, I would expect it to be an *antidote* to serotonin syndrome.
-undopaminergic
Posted by linkadge on June 24, 2020, at 7:35:54
In reply to Re: How does Lumateperone compare to antidepressants?, posted by undopaminergic on June 23, 2020, at 21:32:29
From what I understand, over-activation of the 5-ht1a receptor is part of the process mediating serotonin syndrome (both 5-ht1a and 5-ht2a mediate different aspects of serotonin syndrome). When you block one serotonin receptor, this leaves more serotonin to activate other receptors (i.e. 5-ht1a).
Again, I said the risk was very very low, but there have been case reports of serotonin syndrome when adding atypical antipsychotics to SSRIs.
For example:
https://pubmed.ncbi.nlm.nih.gov/12639169/
(although there is some overlap between the symptoms of serotonin syndrome and neuroleptic malignant syndrome).
Linkadge
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