Lurasidone for the treatment of bipolar depression: an evidence-based review

Figures & data

Figure 1 Three-dimensional structure of lurasidone, also known as (3aR,4S, 7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexy-lmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride or Latuda.

Notes: Molecular weight is 529.13698 g/mol and molecular formula is C₂₈H₃₇ClN₄O₂S. Teal atoms represent hydrogen, gray atoms carbon, red atoms oxygen, blue atoms nitrogen, and the yellow atom a sulfur; the associated hydrogen chloride salt is not pictured.¹⁸

Table 1 Binding profile of the chemical lurasidone: endogenous neurotransmitter, characteristic activity type, and experimental K_i values associated with major receptors

Binding profile of lurasidonea
Receptor	Neurotransmitter	Activity	Binding affinity (Ki)b (nM)
D1	Dopamine	Antagonist	262
D2	Dopamine	Antagonist	1.68±0.09c
5-HT1A	Serotonin	Partial agonist	6.75±0.97
5-HT2A	Serotonin	Antagonist	2.03±0.46
5-HT2C	Serotonin	Antagonist	415
5-HT7	Serotonin	Antagonist	0.495±0.090
α1A	Norepinephrine	Antagonist	47.9±7.8
α2A	Norepinephrine	Antagonist	40.7±7.7
α2C	Norepinephrine	Antagonist	10.8±0.64
H1	Histamine	Antagonist	>1,000
M1	Acetylcholine	Antagonist	>1,000

Notes:

a Experimental values reported by Ishibashi et al.²²

b The equilibrium dissociation constant, decreased value indicated increased affinity.

c Values are means ± standard error of the mean of three or more separate experiments.

Figure 2 Differences among behavioral outcomes by lurasidone treatment regimen between baseline and Week 6 as measured by MADRS score and CGI-BP score.

Notes: (A) Mean change in MADRS from baseline to week 6 across different treatments in patients with bipolar I depression. (B) The mean change in depression severity score on the CGI scale from baseline to week 6 for the same treatment groups. Placebo, 20–60 mg/day and 80–120 mg/day values reported in Loebel’s monotherapy study;³⁹ adjunct experimental values from Loebel et al’s investigation of lurasidone as adjunctive treatment with lithium and valproate.⁴⁰
Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; CGI-BP, Clinical Global Impressions Scale for use in bipolar illness; d, day.

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LoebelACucchiaroJSilvaRLurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled studyAm J Psychiatry2014171216917724170221

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