Systematic Literature Review of Studies Reporting Measures of Functional Outcome or Quality of Life in People with Negative Symptoms of Schizophrenia

Figures & data

Table 1 Summary of Included Publications

Study	Study Number	Patients, n	Inpatient/Outpatient	Planned Duration of Treatment	Male, %	Mean (SD) age, years	Mean (SD) Duration of Disease, Years	Mean (SD) age at Diagnosis, Years
Beck et al 2013^Citation11 (United States)	NR	94	Outpatient	N/A	75.5	Deficit: 39.9 (11.1) Non-deficit: 39.4 (12.2)	NR	NR
Bryl et al 2020^Citation12 (United States)	NR	31	NR	10 weeks	64.5	Dance/movement therapy: 44.67 (10.97) Treatment as usual: 48.38 (12.70)	Dance/movement therapy: 18.94 (11.36) Treatment as usual: 28.92 (11.08)	NR
Buchanan et al 2012^Citation13 (Multinational)	NCT00212836 NCT00265343 NCT00145496 NCT00174265	949	Mainly outpatient	26 weeks	Eastern Hemisphere: Asenapine: 68 Olanzapine: 68.3 Western Hemisphere: Asenapine: 72.1 Olanzapine: 75.9	Eastern Hemisphere: Asenapine: 40.7 (12.7) Olanzapine: 40.3 (11.7) Western Hemisphere: Asenapine: 43.1 (11.4) Olanzapine: 42.8 (11.3)	NR	Eastern Hemisphere: Asenapine: 27.7 (10.3) Olanzapine: 28.1 (9.4) Western Hemisphere: Asenapine: 24.6 (8.0) Olanzapine: 26.2 (9.3)
Burgarski-Kirola et al 2017^Citation14 (Multinational)	NCT01192906 and NCT01192867	Daylyte n=605 and Flashlyte n=594 (ITT population)	NR	24 weeks	Daylyte: 69.2 Flashlyte: 67.6	Daylyte: Bitopertin 5 mg: 42.0 (11.8) Bitopertin 10 mg: 39.8 (11.3) Placebo: 42.3 (12.0) Flashlyte: Bitopertin 10 mg: 41.1 (11.2) Bitopertin 20 mg: 38.2 (12.0) Placebo: 38.7 (12.3)	NR	NR
Dunayevich et al 2017^Citation15 (Multinational)	NCT01568216 and NCT01568229	232	NR	12 weeks	67.2	43.9 (10.5)	NR	NR
Edgar et al 2014^Citation16 (Multinational)	NCT00616798	323	Outpatient	NR	64	Median approx. 40	Approx. 11.5	NR
Rofail et al 2016^Citation17 (Multinational)	NCT00616798	312	NR	8 weeks	64.1	39.9 (10.1)	11.6 (9.0)	NR
Umbricht et al 2014^Citation18 (Multinational)	NCT00616798	323	NR	8 weeks	Bitopertin 10 mg: 68 Bitopertin 30 mg: 53 Bitopertin 60 mg: 62 Placebo: 56	Bitopertin 10 mg: 41.1 (10.4) Bitopertin 30 mg: 40.7 (9.4) Bitopertin 60 mg: 38.9 (9.5) Placebo: 39.0 (10.8)	NR	Bitopertin 10 mg: 25.8 (9.3) Bitopertin 30 mg: 28.5 (9.4) Bitopertin 60 mg: 27.0 (9.6) Placebo: 26.2 (9.8)
Fleischhacker et al 2019^Citation19 (Multinational)	2012–005485-36	456	NR	26 weeks	NR	NR	NR	NR
Nemeth et al 2017^Citation20 (Multinational)	2012–005485-36	460	NR	26 weeks	Cariprazine: 54 Risperidone: 61	Cariprazine: 40.2 (10.5) Risperidone: 40.7 (11.2)	Cariprazine: 11.98 (8.14) Risperidone: 12.96 (9.17)	NR
Hasan et al 2017^Citation21 (Germany)	NCT00783120	73	NR	3 weeks	82.2	Active rTMS: 33.88 (8.88) Sham rTMS: 36.00 (9.86)	NR	NR
Wobrock et al 2015^Citation22 (Germany)	NCT00783120	175	NR	3 weeks	75.2	Active rTMS: 36.2 (10.5) Sham rTMS: 34.9 (9.1)	NR	NR
Hill et al 2011^Citation23 (United States)	NR	32	Outpatient	12 weeks	Folate: 76.5 Placebo: 86.7	Folate: 45.5 Placebo: 46.5	Folate: 20.1 (10.9) Placebo: 19.1 (11.3)	NR
Hirayasu et al 2016^Citation24 (Japan)	JapicCTI-111627	105	Outpatient	52 weeks	68	Bitopertin 5 mg: 41.8 (11.9) Bitopertin 10 mg: 39.9 (12.2) Bitopertin 20 mg: 41.8 (13.8)	NR	NR
Kane et al 2012^Citation25 (United States)	NCT00772005	285	NR	24 weeks	Armodafinil: 75% Placebo: 64%	Armodafinil 43.8 (10.55) Placebo 42.4 (10.07)	Armodafinil: 18.0 (10.96) Placebo: 16.7 (9.86)	NR
Kaphzan et al 2014^Citation26 (Israel)	NCT00192855	50	NR	12 weeks	73.3	Entacapone: 41.8 (2.7) Placebo: 43.8 (2.3)	Entacapone: 18.7 (10.4) Placebo: 18.9 (12.8)	NR
Kayo et al 2020^Citation27 (Brazil)	NCT00791882	62	Outpatient	20 weeks	70.9	NR	16.3 (SD not reported)	NR
Klingberg et al 2011^Citation28 (Germany)	ISRCTN 25455020	198	Outpatient	9 months	56.1	36.9 (9.9)	NR	NR
Klingberg et al 2012^Citation29 (Germany)	ISRCTN 25455020	198	NR	9 months	56.1	36.9 (9.9)	NR	NR
Levkovitz et al 2011^Citation30 (Israel)	NR	15	NR	4 weeks	73.3	32.73 (11.18)	NR	24.86 (10.69)
Liu et al 2012^Citation31 (Taiwan)	NA	50	Inpatients	NA	46	31.1 (7.5)	8.1 (5.9)	21.6 (6.3)
Mairs et al 2011^Citation32 (United Kingdom)	NR	8	NR	NR	75	33 (9.2)	6.1 (5.1)	NR
Novick et al 2017^Citation33 (Multinational)	NA	3,712	Outpatient	NA	Olanzapine: 59.4 Other atypicals: 55.7 Typicals: 53.8	Olanzapine: 38.6 (12.6) Other atypicals: 40.1 (12.4) Typicals: 40.9 (11.9)	Olanzapine: 10.5 (10.5) Other atypicals: 11.7 (10.8) Typicals: 12.5 (10.3)	Mean (SD) age at first contact:Olanzapine: 28.4 (10.1) Other atypicals: 28.5 (10.1) Typicals: 28.6 (9.7)
Palm et al 2016^Citation34 (Germany)	NCT01378078	20	NR	2 weeks	75	36.1 (11.4)	10.5 (9.9)	28.5 (10.6)
Priebe et al 2016a^Citation35 (United Kingdom)	ISRCTN842165587	275	Outpatient	10 weeks	74	42.2 (10.7)	Median 12.6 (IQR, 9.1)	NR
Priebe et al 2016b^Citation36 (United Kingdom)	ISRCTN842165587	275	Outpatient	10 weeks	74	42.2 (10.7)	Median 11 (IQR 7 to 18)	NR
Savill et al 2016^Citation37 (United Kingdom)	ICTRN842165587	275	Outpatient	Approx. 3 months	73.8	42.2 (10.65)	13.6 (9.1)	NR
Rabinowitz et al 2013^Citation38 (United States)	NR	577	76% outpatient	Up to 18 months	NR	NR	NR	NR
Rabinowitz et al 2019^Citation39 (Multinational)	NR	244	NR	12 weeks	NR	NR	NR	NR
Rohricht et al 2011^Citation40 (United Kingdom)	NR	18	Outpatient	10 weeks	88.9	41.2 (11.4)	18.5 (8.4)	NR
Schaefer et al 2020^Citation41 (Germany)	NCT00148616	13	Inpatient	24 weeks	84.6	Memantine: 26.1 (6.4) Placebo: 26.8 (6.7)	NR	Memantine: 20.7 (3.8) Placebo: 20.3 (1.4)
Schoemaker et al 2014^Citation42 (Multinational)	NCT00725075	215	NR	12 weeks	62.1	Org 25,935 4.8 mg BID: 37.4 (9.5) Org 25,935 12–16 mg BID: 38.8 (11.0) Placebo: 38.1 (10.5)	NR	NR
Shoja Shafti et al 2016^Citation43 (Iran)	NR	50	Inpatients	8 weeks	100	Modafinil 42.18 (5.91) Placebo 39.36 (6.37)	Modafinil: 12.30 (3.78)Placebo: 11.47 (4.23)	NR
Stauffer et al 2013^Citation44 (Multinational)	NR	167	Both	16 weeks	77.4	43.3 (10.71)	18.3 (11.25)	NR
Sum et al 2018^Citation45 (Singapore)	NR	58	NR	N/A	63.8	34.24 (9.25)	8.02 (8.32)	26.22 (6.91)
Valiengo et al 2020^Citation46 (Brazil)	NCT02535676	100	NR	5 days	80	Active tDCS group: 34.6 (8.4) Sham tDCS group: 35.9 (10.1)	Active tDCS group: 14.2 (8.1)Sham tDCS group: 14.1 (8.7)	NR
Walling et al 2016^Citation47 (Multinational)	NCT01488929	477	Outpatient	24 weeks	62.3	TC5619 5 mg: 40.0 TC5619 50 mg: 38.4 Placebo: 38.6	NR	NR

Abbreviations: NR, not reported; rTMS, repetitive transcranial magnetic stimulation; SD, standard deviation; tDCS, transcranial direct current stimulation.

Table 2 Functional Outcome Measures Identified in the Literature Review

Study	Study Number	PSP	GAF	UPSA-B	Objective Social Outcomes Index (SIX)	Sheehan Disability Scale	Social Network Schedule	Time Use Survey	GAS	Index of Functioning	Social Functioning Scale	Social Skills Inventory	SOFAS	WHO-DAS 2.0	Work and Social Adjustment Scale
Total number publications		11	7	3	2	2	2	2	1	1	1	1	1	1	1
Total number of studies		10	5	3	1	2	1	1	1	1	1	1	1	1	1
Beck et al 2013^Citation11 (United States)	NR			✓
Bryl et al 2020^Citation12 (United States)	NR					✓								✓
Buchanan et al 2012^Citation13 (Multinational)	NCT00212836 NCT00265343 NCT00145496 NCT00174265
Burgarski-Kirola et al 2017^Citation14 (Multinational)	NCT01192906 NCT01192867	✓
Dunayevich et al 2017^Citation15 (Multinational)	NCT01568216 and NCT01568229	✓				✓
Edgar et al 2014^Citation16 (Multinational)	NCT00616798	✓
Rofail et al 2016^Citation17 (Multinational)	NCT00616798	✓
Umbricht et al 2014^Citation18 (Multinational)	NCT00616798	✓
Fleischhacker et al 2019^Citation19 (Multinational)	2012–005485-36	✓
Nemeth et al 2017^Citation20 (Multinational)	2012–005485-36	✓
Hasan et al 2017^Citation21 (Germany)	NCT00783120		✓
Wobrock et al 2015^Citation22 (Germany)	NCT00783120		✓
Hill et al 2011^Citation23 (United States)	NR		✓
Hirayasu et al 2016^Citation24 (Japan)	JapicCTI-111627	✓
Kane et al 2012^Citation25 (United States)	NCT00772005	✓
Kaphzan et al 2014^Citation26 (Israel)	NCT00192855
Kayo et al 2020^Citation27 (Brazil)	NCT00791882											✓
Klingberg et al 2011^Citation28 (Germany)	ISRCTN 25455020		✓
Klingberg et al 2012^Citation29 (Germany)	ISRCTN 25455020		✓
Levkovitz et al 2011^Citation30 (Israel)	NR												✓
Liu et al 2012^Citation31 (Taiwan)	NA
Mairs et al 2011^Citation32 (United Kingdom)	NR														✓
Novick et al 2017^Citation33 (Multinational)	NA
Palm et al 2016^Citation34 (Germany)	NCT01378078
Priebe et al 2016a^Citation35 (United Kingdom)	ISRCTN84216587				✓		✓	✓
Priebe et al 2016b^Citation36 (United Kingdom)	ISRCTN842165587				✓		✓	✓
Savill et al 2016^Citation37 (United Kingdom)	ICTRN842165587
Rabinowitz et al 2013^Citation38 (United States)	NR									✓
Rabinowitz et al 2019^Citation39 (Multinational)	NR	✓
Rohricht et al 2011^Citation40 (United Kingdom)	NR										✓
Schaefer et al 2020^Citation41 (Germany)	NCT00148616								✓
Schoemaker et al 2014^Citation42 (Multinational)	NCT00725075		✓
Shoja Shafti et al 2016^Citation43 (Iran)	NR
Stauffer et al 2013^Citation44 (Multinational)	NR	✓		✓
Sum et al 2018^Citation45 (Singapore)	NR
Valiengo et al 2020^Citation46 (Brazil)	NCT02535676		✓
Walling et al 2016^Citation47 (Multinational)	NCT01488929			✓

Abbreviations: GAF, Global Assessment of Functioning; GAS, Global Assessment Scale; NR, not reported; PSP, Personal and Social Performance Scale; SOFAS, Social and Occupational Functioning Assessment; UPSA-B, University of California San Diego Performance-Based Skills Assessment Brief Version; WHO-DAS 2.0, World Health Organization Disability Assessment Scale 2.0.

Table 3 Quality of Life Measures Identified in the Literature Review

Study	Study Number	MANSA	EQ-5D	QLS	SQLS	Subjective Well-Being Under Neuroleptic Treatment-Short Form	Psychological General Well-Being Schedule/Index	Quality of Life Scale, abbreviated (Bilker et al 2003)	Q-LES-Q-18 Quality of Life Index	SF-12	SF-6D	WHOQOL BREF
Number of publications,		4	3	3	3	2	1	1	1	1	1	1
Number of studies		2	2	6	1	2	1	1	1	1	1	1
Beck et al 2013^Citation11 (United States)	NR							✓
Bryl et al 2020^Citation12 (United States)	NR
Buchanan et al 2012^Citation13 (Multinational)	NCT00212836 NCT00265343 NCT00145496 NCT00174265			✓
Burgarski-Kirola et al 2017^Citation14 (Multinational)	NCT01192906 and NCT01192867
Dunayevich et al 2017^Citation15 (Multinational)	NCT01568216 and NCT01568229								✓
Edgar et al 2014^Citation16 (Multinational)	NCT00616798				✓
Rofail et al 2016^Citation17 (Multinational)	NCT00616798				✓
Umbricht et al 2014^Citation18 (Multinational)	NCT00616798				✓
Fleischhacker et al 2019^Citation19 (Multinational)	2012–005485-36
Nemeth et al 2017^Citation20 (Multinational)	2012–005485-36
Hasan et al 2017^Citation21 (Germany)	NCT00783120
Wobrock et al 2015^Citation22 (Germany)	NCT00783120
Hill et al 2011^Citation23 (United States)	NR			✓
Hirayasu et al 2016^Citation24 (Japan)	JapicCTI-111627
Kane et al 2012^Citation25 (United States)	NCT00772005
Kaphzan et al 2014^Citation26 (Israel)	NCT00192855			✓ (assumed)
Kayo et al 2020^Citation27 (Brazil)	NCT00791882
Klingberg et al 2011^Citation28 (Germany)	ISRCTN 25455020
Klingberg et al 2012^Citation29 (Germany)	ISRCTN 25455020
Levkovitz et al 2011^Citation30 (Israel)	NR
Liu et al 2012^Citation31 (Taiwan)	NA
Mairs et al 2011^Citation32 (United Kingdom)	NR
Novick et al 2017^Citation33 (Multinational)	NA
Palm et al 2016^Citation34 (Germany)	NCT01378078					✓
Priebe et al 2016a^Citation35 (United Kingdom)	ISRCTN84216587	✓	✓
Priebe et al 2016b^Citation36 (United Kingdom)	ISRCTN842165587	✓	✓
Savill et al 2016^Citation37 (United Kingdom)	ICTRN842165587	✓
Rabinowitz et al 2013^Citation38 (United States)	NR									✓	✓
Rabinowitz et al 2019^Citation39 (Multinational)	NR
Rohricht et al 2011^Citation40 (United Kingdom)	NR	✓
Schaefer et al 2020^Citation41 (Germany)	NCT00148616
Schoemaker et al 2014^Citation42 (Multinational)	NCT00725075
Shoja Shafti et al 2016^Citation43 (Iran)	NR						✓
Stauffer et al 2013^Citation44 (Multinational)	NR		✓			✓
Sum et al 2018^Citation45 (Singapore)	NR											✓
Valiengo et al 2020^Citation46 (Brazil)	NCT02535676
Walling et al 2016^Citation47 (Multinational)	NCT01488929

Abbreviations: MANSA, Manchester Short Assessment of Quality of Life; QLS, Quality of Life Scale; SQLS, Schizophrenia Quality of Life Scale; WHOQOL-BREF, World Health Organization Quality of Life Brief Assessment.

Figure 1 Summary of literature review process.

Note: This figure represents the number of publications not the number of individual studies; some publications included more than one study and some studies were captured in multiple publications. Articles classed as not reporting trial or observational study results included case studies, narrative reviews, protocols, etc. A 10-year time horizon was applied to searches, despite this, multiple articles were excluded during first-round screening owing to publication outside the timeframe of the review.

Abbreviation: QoL, quality of life.

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