Download File - Open Source Psychiatry

Lurasidone/Latuda
1. why should it work?
—some dope pharmacodynamics - blocks D2, partial agonist at 5HT-1, antagonist at
5HT-2 and 5HT-7; no significant affinity for H1 and M1 receptors! also only weak
affinity for the alpha-2 adrenergic receptor, which correlates with its lower risk of
producing orthostasis
2. does it work?
—FDA approved for schizophrenia, bipolar monotherapy, and bipolar augmentation
at a range of 20 mg to 120 mg
--4 or 5 point difference on the MADRS
--when we look at differences in response and remission rates it’s actually pretty
good, 15 to 20% separation from placebo (number needed to treat/NNTs of 5 to 6)
awesome
—AJP, 2014, augmentation study - completion rate of 75 to 80% (many bipolar
studies with much higher dropout rates! for example in the seminal BOLDER study
leading to the approval of quetiapine for bipolar depression the completion rate was
54% in patients taking 600 mg/day and 67% in patients taking 600 mg/day),
indicating it is truly well-tolerated; also tolerability even better for patients with
schizophrenia, 8% discontinuation rate versus 4% for placebo
—great study design for augmentation - worked with both Depakote and Lithium also patients more “real-world,” included those with rapid cycling
—also, on the MADRS, subscales worked across domains producing significant
improvements compared to placebo in sadness, lassitude, inability to feel,
pessimistic thoughts, and sleep in the augmentation study; in the monotherapy
study worked in these domans and also inner tension, 7/10 MADRS subscales
—jmprovements in functional outcomes
—like any antipsychotic, it produces side effects of EPS and akathisia BUT the
absence of or minimal weight gain and other adverse metabolic effects in multiple
studies and multiple treatment populations (mood and psychosis) is impressive! can
be thought of as comparable to Geodon metabolically but without the QT problems
cardiovascularly
—for augmentation in mood studies, relatively rapid response with separation from
placebo beginning in week 3
—although studies were international, the majority of patients/study sites were U.S.
bummer
—bipolar 1 patients only…
—cost
—it does raise prolactin a little but way less than halperidol, risperidone, or zyprexa
how to use this drug
—can be taken once daily, usually at night; for full absorption must be taken with a
meal or within 30 minutes of eating; meal 350 - 1000 cal; doesn’t have to be fatty;
similar to Gedon absorption can be reduced by 1/2 to 2/3 without food
—most studies patients taking doses greater than 80 mg; no significant differences
in adverse effects between lower and higher doses
—for bipolar I, a reasonable titration schedule is the following: 20 mg/day for days
1-2, 40 mg/day for days 3-4, 60 mg/day for days 5-6, 80 mg/da on day 7; from 80
mg, adjust by 20 mg increments q 1 week if necessary
—if using as an augmenting agent, same titration as above but hold at 60 mg rather
than 80 mg for 1 week prior to adjusting in 20 mg increments
—higher may not be better: in the monotherapy study, 20 - 60 mg doses were as
effective as 80 to 120 mg
—most common side effects: nausea, headache, akathisia, and somnolence