title: The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder.
abstract: The treatment of bipolar depression is one of the most challenging issues in contemporary psychiatry. Currently only quetiapine, the olanzapine-fluoxetine combination and recently lurasidone are officially FDA-approved against this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of lurasidone fit to a previously developed model which was the first to be derived on the basis of the strict combination of clinical and preclinical data with no input from theory or opinion. The authors performed a complete and systematic review of the literature to identify the pharmacodynamic properties of lurasidone. The original model suggests that a constellation of effects on different receptors are necessary but the serotonin reuptake inhibition does not seem to play a significant role for bipolar depression. On the contrary norepinephrine activity seems to be very important. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition is essential in order to sustain it. Overall the properties of lurasidone fit well the model and add to its validity. A point that needs clarification is norepinephrine reuptake inhibition which is not yet studied for lurasidone.
authors.affiliation: 3rd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Greece. Electronic address: kfount@med.auth.gr.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Fountoulakis
authors.affiliation: Department of Basic Biological Science, Laboratory of Biology, School of Medicine, University of Athens, Greece. Electronic address: maria.gazouli@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.affiliation: Department of Psychiatry, Laboratory of Psychiatric Genomics, University of California, San Diego and VA San Diego Healthcare System, La Jolla, CA, USA. Electronic address: jkelsoe@ucsd.edu.
authors.forename: John
authors.initials: J
authors.lastname: Kelsoe
authors.affiliation: International Mood Disorders Center, University of California at San Diego, CA, USA. Electronic address: hakiskal@ucsd.edu.
authors.forename: Hagop
authors.initials: H
authors.lastname: Akiskal
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D006801:Humans; D000069056:Lurasidone Hydrochloride / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016239:MEDLINE / Q000706:statistics & numerical data
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000069056:Lurasidone Hydrochloride
keywords: Biological models; Bipolar depression; Bipolar disorder; Lurasidone; Neurobiology