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Aripiprazole: Difference between revisions

From Pharmacopedia
[checked revision][checked revision]
home-claude house-rule fix (terminology)
Safety wave: FDA 2016 impulse-control labeled Warning (May 3 2016 DSC); labeled, not boxed
 
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| legal            = [[USLegal:Prescription only|Rx-only]] in US. Carries the atypical-neuroleptic '''Boxed Warning''' for increased mortality in elderly patients with dementia-related psychosis, and the antidepressant suicidality '''Boxed Warning''' when used for MDD adjunct in patients under 24<ref name="abilify-label" />
| legal            = [[USLegal:Prescription only|Rx-only]] in US. Carries the atypical-neuroleptic '''Boxed Warning''' for increased mortality in elderly patients with dementia-related psychosis, and the antidepressant suicidality '''Boxed Warning''' when used for MDD adjunct in patients under 24<ref name="abilify-label" />
| mechanism        = <vote slug="aripiprazole-mech-claim">'''D2 and D3 dopamine receptor partial agonist''' (the third-generation neuroleptic signature, distinct from olanzapine/risperidone full D2 antagonism), with additional 5-HT1A partial agonism and 5-HT2A receptor antagonism. The D2 partial agonism is the "dopamine system stabilizer" rationale: in hyperdopaminergic states (psychosis, mania) aripiprazole functions as a partial antagonist; in hypodopaminergic states (prefrontal cortex, MDD adjunct) it functions as a partial agonist.</vote> '''Akathisia''' is the most common dose-limiting adverse effect, particularly with the MDD-adjunct dose range. Lower weight gain, lower metabolic burden, and lower prolactin elevation than most second-generation neuroleptics, the principal pharmacological selling points. CYP2D6 and CYP3A4 metabolism; CPIC PGx guidance applies for CYP2D6 dose individualization<ref name="abilify-label" />.
| mechanism        = <vote slug="aripiprazole-mech-claim">'''D2 and D3 dopamine receptor partial agonist''' (the third-generation neuroleptic signature, distinct from olanzapine/risperidone full D2 antagonism), with additional 5-HT1A partial agonism and 5-HT2A receptor antagonism. The D2 partial agonism is the "dopamine system stabilizer" rationale: in hyperdopaminergic states (psychosis, mania) aripiprazole functions as a partial antagonist; in hypodopaminergic states (prefrontal cortex, MDD adjunct) it functions as a partial agonist.</vote> '''Akathisia''' is the most common dose-limiting adverse effect, particularly with the MDD-adjunct dose range. Lower weight gain, lower metabolic burden, and lower prolactin elevation than most second-generation neuroleptics, the principal pharmacological selling points. CYP2D6 and CYP3A4 metabolism; CPIC PGx guidance applies for CYP2D6 dose individualization<ref name="abilify-label" />.
| effects          = In May 2016 the FDA warned that aripiprazole can cause intense, uncontrollable urges, most often compulsive gambling, but also compulsive eating, shopping, and hypersexuality; these urges can arise at any dose, are easily missed, and generally resolve when the dose is lowered or the medicine is stopped.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about new impulse-control problems associated with mental health drug aripiprazole (Abilify, Abilify Maintena, Aristada). May 3, 2016.</ref> The association is commonly linked to aripiprazole's dopamine D2 partial agonism, though the FDA stated the mechanism is not established. This is a labeled Warning, separate from the medicine's boxed warnings.
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