Lurasidone is a newer second-generation antipsychotic drug that is a full antagonist at dopamine D2 and serotonin 5HT2A receptors. It also has antagonist effects at 5HT7 receptors and is a partial agonist at 5HT1A receptors. Lurasidone has minimal affinity for receptors like alpha1, 5HT2C, histamine H1, and muscarinic M1, which predicts a lower risk of side effects like orthostatic hypotension, weight gain, and anticholinergic effects. Lurasidone has been approved by the FDA for the treatment of schizophrenia and bipolar depression.

1. LURASIDONE:- NEWER
ANTIPSYCHOTIC
Dr. V. K. Saini
Resident (Psychiatry)
S.P. Medical College, Bikaner

2. INTRODUCTION
 Lurasidone is a newer second-generation
antipsychotic .
 Lurasidone belongs to the chemical class of
benzoisothiazol derivatives.
 It was approved by U.S.FDA-
- for Schizophrenia – in 2010
- for Bipolar Depression – in 2013

3. MECHANISM OF ACTION
 Lurasidone is a full antagonist at dopamine
D2 and serotonin 5HT2A receptors, properties
shared by most second-generation
antipsychotics.
 Lurasidone is antagonist at serotonin 5HT7
receptor and partial agonist at 5HT1A
receptors; these properties can be potentially
related to effects on cognition and mood.

4.  Lurasidone has minimal affinity for alpha 1
noradrenergic receptor - lower risk for
orthostatic hypotension .
 Lurasidone has minimal/no affinity for 5HT2C
receptors and histamine H1 predicts a lower
risk for weight gain as well .
 Lurasidone’s lack of affinity for cholinergic M1
receptors predicts a low propensity for
anticholinergic side effects except sedation.
 But sedation may be speculated due to 5HT
antagonism.

5. PHARMACOLOGICAL PROPERTIES
 Lurasidone is rapidly absorbed, with a time
to maximum concentration of 1 to 3 hours and
a mean half-life of 18 hours for 40 mg
 Lurasidone is metabolized in the liver by the
CYP3A4 enzyme system ,so use of lurasidone
in the presence of strong inducers and
inhibitors of CYP3A4 (such as rifampin and
ketoconazole, respectively) is contraindicated

6.  Food increase the absorption of lurasidone,
should be taken with food atleast 350 calories.
 Dosing of lurasidone need not be modified for
elderly patients with psychosis (ages 65–85
years), as lurasidone concentrations when dosed
at 20 mg/d were similar to those in young
subjects.
 However, patients with moderate or severe renal
and hepatic impairment will require a dose
adjustment to no greater than 40 mg/d

7. Efficacy of lurasidone in schizophrenia
 A total of 5 randomized controlled trials (6 weeks)
were used in the FDA’s evaluation were conducted
comparing lurasidone with placebo, of which 4
considered as positive demonstrating efficacy &
greater reduction in PANSS and CGI-S as compared with
olanzapine,haloperidol and placebo.#
 In a pooled analysis of 4 short-term, placebo-
controlled studies, lurasidone significantly improved
depressive symptoms in patients with schizophrenia.*
# Leslie Citrome. Lurasidone for Schizophrenia: A Brief Review of a New Second-Generation
Antipsychotic. Clinical Schizophrenia & Related Psychoses January 2011
*Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-
week, placebo-controlled studies.Nasrallah HA,Cucchiaro JB,Mao Y,Pikalov AA,Loebel AD. CNS
Spectr2015 Apr;20(2):140-7.)

8.  A randomised, double-blind, 12-month trials that include
comparison OF Lurasidone with risperidone .Lurasidone
was associated with comparable improvement in efficacy,
with similar relapse rates at 12 months but with
significantly greater improvement in cognition .*
 Compared to QutiapineXR, lurasidone treatment for 12
months was non-inferior to QXR in relapse prevention
but associated with lower risk of relapse and
hospitalization, and a high remission rate.#
* Citrome L, Cucchiaro J, Sarma K, Phillips D, Silva R, Tsuchiya S, et al. Long-term safety and tolerability of lurasidone in
schizophrenia: a 12month, double-blind, active-controlled study. Int Clin Psychopharmacol 2012; 27: 165
# Loebel A, Cucchiaro J, Xu J, Sarma K, Pikalov A, Kane JM. Effectiveness of lurasidone v. quetiapine XR for relapse
prevention in schizophrenia: a 12-month, double-blind, noninferiority study. Schizophr Res 2013; 147: 95-
102.

9. Lurasidone in Bipolar Depression
Lurasidone was safe and well tolerated in this bipolar
depression up to 2 years. Relapse rate was lesser in
monotheraphy group as compared to adjunctive
theraphy and with minimal effects on weight and
metabolic parameters. *
Lurasidone adjunctive with lithium or valproate
demonstrated significant improvement in depressive
symptoms based on the MADRS from weeks 2–5 .
Adverse events most frequently reported for lurasidone
were akathisia, somnolence, and extrapyramidal side
effects. **
* Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of
treatment. Andrei Pikalov,Joyce Tsai, Yongcai Mao, Robert Silva, Josephine Cucchiaro and Antony Loebe.
International Journal of Bipolar Disorders2017 5:9
**Lurasidone adjunctive with lithium or valproate for bipolar depression: A placebo-controlled trial utilizing
prospective and retrospective enrolment cohorts. Trisha Suppes, Hans Kroger, Andrei Pikalov, Antony Loeb.
Int J Psy Res July 2016

10.  6 week double-blind, placebo-controlled, fixed-
flexible dose study established the efficacy of
lurasidone as a monotherapy treatment* for
bipolar depression and another study with
adjunct to sod.valprote /Li**. Both the studies
found that lurasidone group had greater
improvement as compared to placebo.
*Loebel A, Cucchiaro J, Silva R, et al. Lurasidone monotherapy in the treatment of bipolar I depression: a
randomized, double-blind, placebocontrolled study. Am J Psychiatry. 2014;171(2):160–168. 40.
**Loebel A, Cucchiaro J, Silva R, et al. Lurasidone as adjunctive therapy with lithium or valproate for the
treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J
Psychiatry. 2014;171(2): 169–177. 41

11. TOLERABILITY
• Most Common treatment-emergent adverse
events
• Somnolence
• Akathisia
• Nausea
• Parkinsonism
• Agitation
Int J Clin Pract. 2011;65(2):189-210
Clin Schizophr Relat Psychoses. 2011;4(4):251-7

12. Lower risk of Weight gain
Lurasidone demonstrated lower risk of weight gain
compared to olanzapine and risperidone
Int Clin Psychopharmacol. 2012;27(3):165-76

13. Lurasidone associated with less Prolactinemia
and better metabolic profile
CNS Spectr. 2016;6:1-10Int Clin Psychopharmacol. 2012;27(3):165-76

14. Better cardiac profile
• Lurasione associated with good cardiovascular
tolerability and lesser QTc prologation.*
*Comparative efficacy and tolerability of 15 antipsychotic drugs in
schizophrenia: a multiple-treatments meta-analysis. Leucht
S, Cipriani A,Spineli L, Mavridis D, Orey D,Richter F et al. Lancet.
2013;382(9896):951-62.

15. Side effects : Lurasidone v/s Other Antipsychotics
Ther Clin Risk Manag. 2011; 7: 239–250

16. **p<0.01
Change in Neurocognitive Z-scores from
Baseline to Month 6
N=167 patients with acute schizophrenia; Age=18 to 75
years; Dose=Lurasidone 40-160 mg/day and quetiapine
XR 200-600 mg/day;
T= 6 month
Better Cognitive Profile
Significant
improvement in
cognitive performance
compared to
quetiapine XR

17. SUMMARY
 Lurasidone is newer antipsychotic along with D2
blocking property has antagonistic activity at
5HT2A,5HT2C and 5HT7 receptors & partial agonism at
5HT1A receptor.
 Minimal /No affinity for M1,Alpha &H1 receptor.
 US FDA approved for Schizophrenia & Bipolar
Depression.
 Should be taken with food.
 Should be avoided with CYP3A4 inhibitor/inducers.
 Most common observed adverse effects are
somnolence, akathasia, nausea ,parkinsonism etc.

18.  Advantages of LURASIDONE–
Better lipid profile, lesser change in glucose level
and less risk of weight gain
Lesser chances of Hyperprolactinemia and EPS
due to 5HT2a &5HT7 antagonism
Least cognitive &memory deficit due to lack of
anticholinergic effect
Lesser risk of QT prolongation
No adjustment in dose required in elderly