Schizophrenia Treatment with Second-Generation Antipsychotics: A Multi-Country Comparison of the Costs of Cardiovascular and Metabolic Adverse Events and Weight Gain

Figures & data

Table 1 Clinical Effectiveness Evidence: Short-Term and Long-Term Outcomes

	Short-Term Outcomes (Up to 13 Weeks)								Long-Term Outcomes (Up to Three Years)
	Treatment Discontinuation (RR)	Weight Gain (kg)	High-Density Lipoprotein Cholesterol (mmol/L)	Total Cholesterol (mmol/L)	Fasting Triglycerides (mmol/L)	Fasting Plasma Glucose (mmol/L)	Prolactin Elevation (ng/mL)	QTc Prolongation (ms)	Relapse (RR)	Discontinuation Due to AEs (RR)	Weight Gain (kg)	Fasting Plasma Glucose (mmol/L)
Lurasidone	0.88	0.32	0.02	−0.03	0	−0.29	7.04	−2.21	0.30	0.97	−0.88	−0.09
Aripiprazole	0.8	0.48	0.04	0.06	0.02	0.13	−7.1	−0.43	0.64	1.34	−0.60	0.02
Brexpiprazole	0.89	0.7	0.05	0.05	−0.01	0.04	0.95	−1.46	0.35	0.45	1.90	0.21
Cariprazine	0.93	0.73	0.02	−0.09	0.01	0.26	−3.19	−1.45	0.52	0.91	0.19	0.07
Olanzapine	0.69	2.78	−0.01	0.4	0.46	0.2	4.47	4.29	0.24	0.58	3.05	0.22
Paliperidone	0.7	1.49	0.01	0.06	0.04	0.08	48.51	1.21	0.26	1.40	2.12	0.12
Quetiapine	0.85	1.94	0.01	0.31	0.32	0.09	−1.17	3.43	0.38	0.69	1.74	0.09
Risperidone	0.82	1.44	0.01	0.06	0.04	0.08	37.98	4.77	0.33	1.02	2.12	0.05
Ziprasidone	0.9	−0.16	0.05	−0.04	0.02	0.05	2.75	9.7	0.28	0.77	−1.35	−0.09
Lumateperone	0.67	0.66	0.02	−0.07	−0.06	−0.08	−1.29	1.98	0.37	0.90	0.92	0.07
Source*	Huhn 2019^Citation9 (NMA of RCTs)		Pillinger 2020^Citation6 (NMA of RCTs)				Huhn 2019^Citation9 (NMA of RCTs)		Zhao 2016^Citation41 (NMA of RCTs)		Multiple* (NMA, trials)	Zhang 2017^Citation42 (NMA of RCTs)

Notes: All comparisons are against placebo; Data are mean differences, unless otherwise indicated; *Short-term evidence for lumateperone is a weighted average of data from Lieberman 2015 and Correll 2020 (RCTs);^22,23 Long-term evidence for brexpiprazole and cariprazine are from Fleischhacker 2017 and Durgam 2016 respectively (RCTs);^24,25 Long-term evidence for lumateperone is not available, so average values for the other antipsychotics were used. Both long-term relative risks for lurasidone were from Kishimoto 2019 (meta-analysis of RCTs);⁴³ See Appendix 4 for details on evidence sources for long-term weight gain.

Abbreviations: AEs, adverse events; RR, relative risk.

Table 2 Country-Specific Annual per Patient Costs (US $)

	France	Hungary	Italy	Slovenia	Spain	Sweden	UK
Weight gain	624	47	229	229	229	463	208
Diabetes	6,677	5,046	3,478	1,242	2,062	3,417	6,553
Fatal CVD event	8,142	4,137	5,178	4,137	10,575	8,175	5,158
CVD event Year 1	23,572	3,006	7,310	11,685	13,557	6,325	4,093
CVD event Years 2+	3,272	1,170	6,405	496	11,060	2,207	1,702
Metabolic syndrome	970	970	970	970	970	970	970
Hyperprolactinaemia	172	83	197	83	360	860	404
QT prolongation	441	129	493	129	477	1,461	832
Stable disease	1,508	612	341	1,089	4,949	10,826	2,497
Relapse	13,707	3,960	1,746	13,352	9,866	16,687	10,605
Treatment switching	330	97	370	97	358	1,096	624

Abbreviation: CVD, cardiovascular disease; includes country-specific proportions of stroke and myocardial infarction.

Figure 1 Model schematic (patient health states).

Abbreviation: CVD, cardiovascular disease.

Table 3 Lifetime Costs, Patients Initiating Acute Treatment (Country-Specific Currencies)

	France (€)	Hungary (HUF)	Italy (€)	Slovenia (€)	Spain (€)	Sweden (SEK)	UK (£)
Lurasidone	60,504	4,020,850	39,828	24,459	67,028	926,893	42,262
Ziprasidone	67,714	4,695,375	46,217	24,526	69,351	931,621	48,135
Aripiprazole	82,391	5,863,345	54,843	29,665	76,136	1,076,633	58,924
Risperidone	84,163	5,862,550	58,202	27,919	75,304	1,070,426	59,264
Brexpiprazole	85,697	6,221,213	59,545	27,919	75,073	1,071,224	61,399
Quetiapine	88,911	6,385,937	61,545	29,710	78,557	1,105,502	62,458
Paliperidone	86,969	6,279,349	61,088	28,621	76,374	1,086,452	63,624
Cariprazine	89,945	6,760,236	61,538	30,429	77,669	1,130,224	66,047
Lumateperone	94,115	8,869,189	68,497	41,789	88,634	1,229,085	70,374
Olanzapine	108,267	8,424,887	78,386	32,193	85,071	1,248,390	77,727

Table 4 Lifetime Costs, Patients Initiating Maintenance Treatment (Country-Specific Currencies)

	France (€)	Hungary (HUF)	Italy (€)	Slovenia (€)	Spain (€)	Sweden (SEK)	UK (£)
Ziprasidone	69,950	4,909,048	48,538	24,932	70,486	935,980	50,061
Lurasidone	71,960	5,109,301	49,590	26,055	71,306	989,858	52,063
Aripiprazole	82,795	5,839,141	55,156	30,158	76,456	1,083,370	59,733
Risperidone	84,367	5,928,102	58,504	28,198	75,427	1,070,048	60,289
Cariprazine	83,487	6,011,674	56,611	29,589	76,035	1,079,753	60,670
Quetiapine	85,504	6,059,230	59,188	28,602	76,000	1,075,033	61,189
Paliperidone	86,969	6,279,349	61,088	28,621	76,374	1,086,452	63,624
Brexpiprazole	90,730	6,652,409	63,910	28,876	77,331	1,107,355	65,858
Olanzapine	94,090	6,871,632	67,536	28,501	77,635	1,127,000	67,802
Lumateperone	93,142	7,837,639	66,641	36,066	83,910	1,180,117	69,145

Figure 2 Distribution of lifetime costs (acute population).

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