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Re: Linkadge - Lurasidone - What do you think?

Posted by SLS on January 22, 2011, at 3:46:27

In reply to Re: Linkadge - Lurasidone - What do you think? » linkadge, posted by SLS on January 20, 2011, at 20:37:27

> > Yeah, looks ok in terms of an antipsychotic. The d2 antagonism might be a drawback, if desired as a depression adjunct.

Here is a more comprehensive overview of lurasidone:

Full article:

http://tinyurl.com/4knbgsa


Abstract:

Lurasidone, a new-generation atypical antipsychotic, has been approved by FDA for the treatment of schizophrenia and is under investigation for the treatment of bipolar disorder. In 4 separate clinical trials, lurasidone has demonstrated efficacy in treating schizophrenia, with total Positive and Negative Syndrome Scale scores decreasing by a range of 14 to 17 points depending on the lurasidone dosage. In addition to the studies in schizophrenia, ongoing trials in patients with bipolar disorder are being completed. The most common adverse events associated with lurasidone treatment are nausea, vomiting, akathisia, dizziness, and sedation. Lurasidone has similar affinity for the dopamine D2 and serotonin 5-HT2A receptors, but a much greater affinity for 5-HT7, 5-HT1A, and a2C-adrenergic subtype receptors, than other atypical antipsychotics. Experimental data support the theory that antagonism of 5-HT7 can improve cognition, memory, and mood symptoms. This may provide a unique place for lurasidone in the treatment of schizophrenia and bipolar disorder. (Formulary. 2010;45:313317.)


Excerpts:

In addition to lurasidone's affinity for the D2 and 5-HT2A receptors, it has the highest affinity of any atypical antipsychotic for the 5-HT7 receptor. Experimental data support the theory that antagonism of 5-HT7 can improve cognition, memory, and mood symptoms. Additionally, lurasidone has a much greater affinity for 5-HT1A and a2-adrenergic receptors, which have been implicated in improving cognition, negative symptoms, and mood symptoms, such as depression and anxiety.

Lurasidone has the highest affinity of any atypical antipsychotic for the 5-HT7 receptor. Portions of the brain with a large distribution of 5-HT7 receptors include the thalamic and hypothalamic areas, which are integral to sleep cycles, and the hippocampus, raphe nuclei, and cortical area, which play a role in mood regulation.12 Also, blockade of 5-HT7 in the thalamus, which is an area that aids in sensory functioning, could potentially add to the antipsychotic effect.13 Experimental data support the theory that antagonism of 5-HT7 can improve cognition, memory, and mood symptoms.14,15

In addition to 5-HT7, lurasidone has a much greater affinity for 5-HT1A and a2C-adrenergic subtypes than most atypical antipsychotics.16 Antagonism at these receptors is implicated in improving cognition, negative symptoms, and mood symptoms, such as depression and anxiety.10

The number of subjects with significant weight gain (>7% change in weight) was less with lurasidone than with placebo and olanzapine (5.9%, 6.9%, 34.4%, respectively).

Lurasidone caused a slight increase in weight and BMI, but olanzapine caused a more significant increase

Hyperprolactinemia.Lurasidone has shown evidence of increasing prolactin levels, which is dose dependent and slightly greater in women than men. However, in this study the patients did not experience any adverse events related to this increase in prolactin levels.16

The efficacy data for lurasidone have been evaluated for dosages 20 mg to 120 mg per day. The 20-mg/d dose is less effective in terms of improvement in schizophrenia symptoms compared with higher doses. The 40-mg/d dose has been considered optimal in the outpatient population, and the 80-mg/d dose is more effective in the inpatient population.

The most common adverse events associated with lurasidone treatment are nausea, vomiting, akathisia, dizziness, and sedation. With the propensity of several atypical antipsychotics to cause metabolic disturbances or metabolic syndrome, new medications are needed that minimize this risk. Clinical trials of lurasidone have demonstrated that there are minimal risks for the development of metabolic syndrome. Additionally, there are no significant increases in QTc and only minimal increases in prolactin levels, which are dose dependent.

In addition to lurasidone's affinity for the D2 and 5-HT2A receptors, it has the highest affinity of any atypical antipsychotic for the 5-HT7 receptor. Experimental data support the theory that antagonism of 5-HT7 can improve cognition, memory, and mood symptoms. Additionally, lurasidone has a much greater affinity for 5-HT1A and a2-adrenergic receptors, which have been implicated in improving cognition, negative symptoms, and mood symptoms, such as depression and anxiety.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

 

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