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Apr 28, 2014, 01:31 AM
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Member Since: Oct 2013
Location: Texas
Posts: 340
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Quote:
Originally Posted by Miguel'smom
He doesn't want me on anything sedating or that decreases gray matter.
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Latuda (lurasidone) is mildly sedating about 1 hours after taking it and then it goes anyway a few hours later. I take it at night to help me get to sleep. Come morning it's sedating effects have completely worn off.
Quote:
If you give rats a brain toxin called MK-801, they will become forgetful, as measured by rat activities such as navigating mazes. In preclinical trials, lurasidone did a better job of reversing MK-801-induced memory impairment in rats than risperidone, olanzapine, or quetiapine (Enomoto T et al, Behav Brain Res 2008;186(2):197–207).
Also in rats, lurasidone was shown to upregulate BDNF(brain derived growth factor) in the prefrontal cortex (Fumagalli F et al, Int J Neuropsychopharmacol 2011:14(1):1–12). Since BDNF is decreased in both schizophrenia patients (Weickert CS et al, Mol Psychiatry 2003;8(6):592–610) and animal models of schizophrenia (Fumagalli F et al, Eur J Neurosci 2004;20(5):1348–1354; Roceri M et al, Biol Psychiatry 2004;55(7):708–714), a drug that can upregulate BDNF has theoretical appeal.
But what about lurasidone’s cognitive effects in humans? Thus far, two human studies have examined the question. One administered lurasidone 80 mg or placebo to 180 patients with schizophrenia for six weeks, and showed a small (-2.1 vs -0.5) but significant (p=0.0015) improvement in the cognitive subscale of the PANSS versus placebo (Nakamura M et al, J Clin Psychiatry 2009;70(6):829–836).
That sounds impressive, but the study did not compare lurasidone with other medications. Also, the cognitive subscale of PANSS does not really measure cognitive dysfunction per se, but rather thought patterns common in schizophrenia, such as stereotyped thinking, lack of abstract thinking, and lack of judgment and insight.
The other study in humans was a randomized double-blind three-week trial of lurasidone 120 mg (n=123) versus ziprasidone 80 mg twice daily (n=111) (Harvey PD et al, Schizophr Res 2011;127(1–3):188–194). Two outcome measures were used. One was a subset of tests from the MATRICS Consensus Cognitive Battery (MCCB), which is an interviewer-rated measure of cognitive function.
This showed a small but significant improvement in the lurasidone group, but not the ziprasidone group, which was consistent with a “practice effect.” It’s not clear why the ziprasidone group did not equally benefit from the practice effect, but several other antipsychotics have shown the effect in other studies.
The other outcome measure was the Schizophrenia Cognition Rating Scale (SCoRS). This is a structured 20-question interview of both the patient and an informant that is not susceptible to practice effects, because it measures functionality. The lurasidone group showed statistically significant improvements over three weeks on these measures, whereas the ziprasidone group did not. However, in direct comparisons between the two drugs, lurasidone did not show a statistical benefit over ziprasidone.
So—is lurasidone pro-cognitive, or isn’t it? The jury is still out. All antipsychotics appear to improve cognition to some degree, but the improvements are thought to be either artifacts of practice, or reflections of improvement in general psychotic symptoms (see Dr. Balt’s article in this issue for details). At this point, all we can say for sure is that in trials designed by Sunovion, lurasidone’s manufacturer, lurasidone appears slightly more pro-cognitive than one particular comparator, ziprasidone. Given the proven ability of companies to manipulate study design to make their drugs look better than their competitors’, we will have to await non-sponsored data before drawing clear conclusions.
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Here is a study about Latuda and Modulation of BDNF expression by ... [Int J Neuropsychopharmacol. 2012] - PubMed - NCBI
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