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

Franklin R, Zorowitz S, Corse AK, Widge AS, Deckersbach T - Neuropsychiatr Dis Treat (2015)

Bottom Line: These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea.Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels.However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

ABSTRACT
Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients' lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors; moderate-affinity antagonism at α2C-adrenergic receptors; low- to very low-affinity antagonism at α1A-adrenergic, α2A-adrenergic, H1, M1, and 5-HT2C receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2-3 weeks of treatment (as measured by the Montgomery-Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine-fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.

No MeSH data available.


Related in: MedlinePlus

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
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f1-ndt-11-2143: 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

Mentions: Lurasidone or (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylm-ethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride20 (as it is known chemically) (Figure 1 for 3D chemical structure) is a chemical in the benzisothiazole class, structurally related to perospirone and ziprasidone, as well as the benzisoxazole derivative risperidone.21 In vitro assays have demonstrated that lurasidone is a full antagonist at D2 (Ki=1.68 nM)22 (Table 1) and 5-HT2A (Ki=2.03 nM) receptor subtypes, a property shared by other atypical antipsychotics such as risperidone, olanzapine, quetiapine, clozapine, and aripiprazole.22 In comparison to similar drugs, lurasidone has the highest binding affinity for the 5-HT7 receptor (Ki=0.5 nM).22 Other notable pharmacological properties include moderate-affinity α2C-adrenergic antagonism, partial agonism at the 5-HT1A receptor, and low affinity for the muscarinic (M1), histamine (H1) (both Ki values >1,000 nM), 5-HT2C (415 nM), α1A (47.9 nM), and α2A (40.7 nM) adrenergic receptors.23Table 1 shows the pharmacological profile of lurasidone.


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

Franklin R, Zorowitz S, Corse AK, Widge AS, Deckersbach T - Neuropsychiatr Dis Treat (2015)

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
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4547662&req=5

f1-ndt-11-2143: 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
Mentions: Lurasidone or (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylm-ethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride20 (as it is known chemically) (Figure 1 for 3D chemical structure) is a chemical in the benzisothiazole class, structurally related to perospirone and ziprasidone, as well as the benzisoxazole derivative risperidone.21 In vitro assays have demonstrated that lurasidone is a full antagonist at D2 (Ki=1.68 nM)22 (Table 1) and 5-HT2A (Ki=2.03 nM) receptor subtypes, a property shared by other atypical antipsychotics such as risperidone, olanzapine, quetiapine, clozapine, and aripiprazole.22 In comparison to similar drugs, lurasidone has the highest binding affinity for the 5-HT7 receptor (Ki=0.5 nM).22 Other notable pharmacological properties include moderate-affinity α2C-adrenergic antagonism, partial agonism at the 5-HT1A receptor, and low affinity for the muscarinic (M1), histamine (H1) (both Ki values >1,000 nM), 5-HT2C (415 nM), α1A (47.9 nM), and α2A (40.7 nM) adrenergic receptors.23Table 1 shows the pharmacological profile of lurasidone.

Bottom Line: These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea.Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels.However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.

View Article: PubMed Central - PubMed

Affiliation: Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

ABSTRACT
Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients' lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors; moderate-affinity antagonism at α2C-adrenergic receptors; low- to very low-affinity antagonism at α1A-adrenergic, α2A-adrenergic, H1, M1, and 5-HT2C receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2-3 weeks of treatment (as measured by the Montgomery-Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine-fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.

No MeSH data available.


Related in: MedlinePlus