Clinical potential of lurasidone in the management of schizophrenia

Figures & data

Table 1 Summary of completed trials with information available for lurasidone

Authors/Trial number	Trial details	Length	Sample	Randomized (n)	Lurasidone (± active comparator)		Outcome (primary endpoint)
					Dose (mg/day)	n
Lurasidone dose–response study
Harvey et al^Citation29	RCT, DB Dose-response study	8 weeks	Inpatients and outpatients with schizophrenia	195	20	65	Limited information available.
					40	72	LOCF analysis demonstrated that single daily doses of 40 and 80 mg of lurasidone were associated with significant improvement from baseline on the PANSS and BPRS.
					80	58
Lurasidone versus placebo studies
D1050006^Citation16	RCT, DB, PC Efficacy and safety study	6 weeks	Acute schizophrenia	149	40	49	Mean BPRS total (SD)
					120	47	Change from baseline (LOCF)
					Placebo	49	−9.4 (1.58, P = 0.02)
							−11 (1.58, P = 0.004)
							−3.8 (1.57)
Nakamura et al^Citation27 (D1050196)	RCT, DB, PC Efficacy and safety study	6 weeks	Acute schizophrenia	180	80	90	Mean BPRS total (SD)
					Placebo	90	Change from baseline (LOCF)
							−8.9 (1.32, P = 0.012)
							−4.2 (1.36)
D1050229 PEARL 1^Citation16	RCT, DB, PC Efficacy and safety study	6 weeks	Acute schizophrenia	500	40	121	Mean PANSS total (SD)
					80	118	Change from baseline (MMRM)
					120	123	−19.2 (1.7, P = 0.59)
					Placebo	124	−23.4 (1.8, P = 0.03)
							−20.5 (1.8, P = 0.39)
							−17.0 (1.8)
Lurasidone with active comparator studies
D1050049^Citation16	RCT, DB, PC Efficacy study	6 weeks	Acute schizophrenia	356	20	71	Mean BPRS total (SD)
					40	67	Change from baseline (LOCF)
					80	71	−5.0 (1.38, P = 0.36)
					Haloperidol 10	72	−5.2 (1.44, P = 0.44)
					Placebo	72	−8.0 (1.40, P = 1.00)
							−9.8 (1.37, P = 0.75)
							−7.9 (1.38)
							This is an inconclusive or failed study.
D1050231 PEARL 2^Citation16	RCT, DB, PC Efficacy and safety study	6 weeks	Acute schizophrenia	478	40	118	Mean PANSS total (SD)
					120	118	Change from baseline (MMRM)
					Olanzapine 15	121	−25.7 (2.0, P = 0.002)
					placebo	114	−23.6 (2.1, P = 0.022)
							−28.7 (1.9, P < 0.001)
							−16.0 (2.1)
D1050233 PEARL 3^Citation34	RCT, DB, PC Efficacy and safety study	6 weeks	Acute schizophrenia	488	80	125	Mean PANSS total
					160	121	Change from baseline (MMRM)
					Quetiapine XR 600	116	−22.2 (P < 0.001)
					Placebo	120	−26.5 (P < 0.001)
							−27.8 (P < 0.001)
							−10.3
Cucchiaro et al^Citation28 (D1050254)	RCT, DB Efficacy, and safety	3 weeks	Stable outpatients with chronic schizophrenia or schizoaffective disorder	301	120	150	Mean PANSS total (SD)
					Ziprasidone 160	151	Change from baseline (MMRM)
							−6.2
							−4.5
							Similar for both treatment groups at week 3 (P > 0.05)
Harvey et al^Citation24 (D1050254)	RCT, DB cognitive assessment						Cognition assessment with MCCB and SCoRS. At endpoint there was a statistical trend (P = 0.058) for lurasidone to improve from baseline SCoRS. There was no significant difference between treatment for changes on the MCCB score.
D1050237 PEARL safety trial^Citation33,Citation34	RCT, DB Long term safety study	12 month	Stable outpatients with chronic schizophrenia or schizoaffective disorder	629	40–120	419	Limited information available
					Risperidone 2–6	202	Better metabolic profile (weight gain, glucose, lipids) for lurasidone compared to risperidone.
							Minimal elevation in prolactin in lurasidone-treated patients (+0.10 versus +9.10; P = 0.001).
							Most frequent lurasidone adverse events were nausea, akathisia and vomiting.

Abbreviations: BPRS, Brief Psychiatric Rating Scale; DB, double-blind; LOCF, last observation carried forward; MCCB, Subset of the MATRICS Consensus Cognitive Battery; MMRM, mixed-effect model repeated measure; PANSS, Positive and Negative Syndrome Scale; PC, placebo-controlled; PEARL, Program to Evaluate the Antipsychotic Response to Lurasidone; RCT, randomized controlled trial; SCoRS, Schizophrenia Cognition Rating Scale; SD, standard deviation.

Table 2 Results of a pooled analysis based on a five-factor model of schizophrenia²⁵

Five PANSS factor scores	Lurasidone 40 mg/day			Lurasidone 80 mg/day			Lurasidone 120 mg/day
	Change from baseline	P	Effect size	Change from baseline	P	Effect size	Change from baseline	P	Effect size
Positive factor	−7.92	<0.001	0.35	−8.48	<0.001	0.47	−8.25	<0.001	0.42
Negative factor	−5.59	<0.001	0.41	−4.96	0.02	0.25	−5.21	0.002	0.31
Disorganized thought	−4.86	<0.001	0.40	−5.10	<0.001	0.47	−5.22	<0.001	0.50
Hostility	−2.33	<0.013	0.25	−2.58	0.002	0.33	−2.87	<0.001	0.44
Depression/anxiety	−3.14	0.002	0.31	−3.23	0.002	0.35	−3.01	0.012	0.26

Notes: Five PANSS factor scores were analysed using MMRM analysis. Adjusted effect sizes were calculated from an ANCOVA analysis (LOCF endpoint) as the between-treatment group difference in least squares mean change scores divided by the pooled standard deviation of the change scores. Reprinted from Schizophrenia Research, 117, Loebel A, Cucchiaro J, Silva R, Ogasa M, Severs J, Marder SR, Efficacy of lurasidone in schizophrenia: Results of a pooled analysis based on a 5-factor model of schizophrenia, 267, 2010, with permission from Elsevier.

Abbreviations: ANCOVA, analysis of covariance; LOCF, last observation carried forward; MMRM, mixed-effect model repeated measure; PANSS, Positive and Negative Syndrome Scale.

Table 3 Common adverse events for lurasidone versus active comparator^28,33,34

Adverse event (%)	Short-term trials						Long-term trials
	D1050254 (3 weeks)		D1050233 PEARL 3 (6 weeks)				D1050237 (12 months)
	Lurasidone 120 mg/day	Ziprasidone 160 mg/day	Lurasidone 80 mg/day	Lurasidone 160 mg/day	Quetiapine 600 mg/day	Placebo	Lurasidone 40–120 mg/day	Risperidone 2–6 mg/day
Akathisia	3.3	6.6	8	9	2	1	14.3	7.9
Nausea	7.3	4.6	8	6.6	3.4	3.3	16.7	10.9
Vomiting	8	4	−	−	−	−	10	3.3
Parkinsonism	−	−	5.6	6.6	3.4	0	4.3	5.4
Somnolence	6.7	9.9	4	6.6	13.4	0.8	13.6	17.8
Sedation	4.7	11.3	−	−	−	−	−	−
Insomnia	10.7	9.3	−	−	−	−	−	−
Headache	6.7	4.6	−	−	−	−	−	−
Dizziness	2.7	6.6	4.8	5.8	13.4	1.7	−	−
Dry mouth	−	−	1.6	1.7	7.6	0.8	−	−
Constipation	−	−	2.4	0.8	6.7	2.5	1.9	6.9
Weight gain	−	−	0.8	1.7	6.7	0.8	9.3	19.8

Table 4 Metabolic effects of lurasidone from short-term trials^16,17

	Placebo	Lurasidone
		20 mg/day	40 mg/day	80 mg/day	120 mg/day
Glucose
Mean change from baseline (mg/dL)	−0.7	−0.6	2.5	−0.9	2.5
≥ 126 mg/dL (%)	8.6	11.7	14.3	10.0	10.0
Total cholesterol
Mean change from baseline (mg/dL)	−8.5	−12.3	−9.4	−9.8	−3.8
≥ 240 mg/dL (%)	6.6	13.8	7.3	6.9	3.8
Triglycerides
Mean change from baseline (mg/dL)	−15.7	−29.1	−6.2	−14.2	−3.1
≥ 200 m g/dL (%)	12.5	14.3	14.0	8.7	10.5
Weight
Mean change from baseline (kg)	0.26	−0.15	0.67	1.14	0.68

Table 5 Adverse effects of lurasidone compared with those of other antipsychotics

Drug	QT prolongation	Hypotension	Sedation	Weight gain	Metabolic syndrome	Extrapyramidal symptoms	Prolactin elevation
Lurasidone	−	−	+	+/–	−	+	+/–*
Amisulpride	+	−	−	+	+	+	+++
Aripiprazole	−	−	−	+/–	+/–	+/–	−
Asenapine	+	−	−	+/–	−	+/–	+/–
Chlorpromazine	++	+++	+++	++	++	++	+++
Clozapine	+	+++	+++	+++	+++	−	−
Haloperidol	++	+	+	+	+	+++	+++
Olanzapine	+	+	++	+++	+++	+/–	+
Paliperidone	+	++	+	++	++	+	+++
Quetiapine	++	++	++	++	++	−	−
Risperidone	+	++	+	++	++	+	+++
Sertindole	+++	+++	−	+	+	−	+/–
Sulpiride	+	−	−	+	+	+	+++
Ziprasidone	+++	+	+	+/–	+/–	+/–	+/–

Notes:

* Short-term trials reported an increase and long-term safety study found no increase in prolactin levels. Adapted from The Maudsley Prescribing Guidelines 10th ed;³⁶ reproduced with permission from the publisher.

Abbreviations: +++, high incidence/severity; ++, moderate incidence/severity; +, low incidence/severity; –, very low incidence/severity.

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