Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years

Table 1 Risk of bias for randomized controlled trials

Ref.	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Abelson et al[67], 2005			-	-	+
Barcia et al[32], 2019		+	-	-	-
Goodman et al[16], 2010			-	-	+
Huff et al[31], 2010					+
Luyten et al[20], 2016	+		-	-
Tyagi et al[17], 2019		+			+	+
Welter et al[39], 2020		+	-	-	-

+: High risk of bias; -: Low risk of bias. If there is no sign, the risk of bias is uncertain.

Table 2 Risk of bias for non-randomized controlled trials

Ref.	Selection	Comparability	Outcome
Anderson and Ahmed[74], 2003	++	+	++
Aouizerate et al[75], 2009	++	+	+++
Azriel et al[76], 2020	++	+	+++
Chabardes et al[29], 2020	++	+	++
Chang et al[77], 2017	++	+	+++
Choudhury et al[78], 2017	++	+	+++
Coenen et al[79], 2017	++	+	+++
Denys et al[44], 2020	++	+	++
Doshi et al[80], 2019	++	+	+++
Farrand et al[42], 2018	++	+	+++
Fayad et al[33], 2016	++	+	+++
Franzini et al[81], 2010	+++	+	+++
Gabriëls et al[53], 2003	++	+	+++
Graat et al[19], 2020	++	+	+++
Grant et al[34], 2016	++	+	+++
Greenberg et al[36], 2010	++	+	+++
Gupta et al[35], 2019	++	+	+++
Holland et al[21], 2020	++	+	+
Huys et al[30], 2019	++	+	+++
Islam et al[40], 2015	++	+	+++
Jiménez et al[55], 2013	++	+	+++
Lee et al[37], 2019	++	+	+++
Maarouf et al[45], 2016	+++	+	++
Mallet et al[22], 2019	++	+	+++
Menchón et al[13], 2021	++	+	++
Mulders et al[82], 2017	++	+	+++
Plewnia et al[83], 2008	++	+	+++
Polosan et al[38], 2019	++	+	+++
Roh et al[61], 2012	++	+	+++
Sachdev et al[84], 2012	++	+	++
Senova et al[85], 2020	++	+	+++
Tsai et al[49], 2012	++	+	++
Winter et al[28], 2021	++	+	+++

Each “+” symbol indicates lower risk of bias.

Table 3 Differences in mean characteristics between the short-term and long-term studies

Characteristic	Short-term		Long-term
	mean ± SD	Range	mean ± SD	Range
Sample size, n	7.9 ± 13.6	1-70	14 ± 14.4	1-50
Female, %	54 ± 36.9	0-100	61.5 ± 22	33-100
Average age, yr	41.7 ± 9.9	28-72	40.5 ± 4.3	32-45
Average duration of illness, yr	24 ± 16.4	5-52	20.4 ± 3.2	16-25
Follow-up since DBS, mo	18.5 ± 8	7-36	63.7 ± 20.7	38-96
Follow-up since DBS, yr	1.5 ± 0.6	1-2.7	5.3 ± 1.7	3-7.7
Baseline Y-BOCS, mean score	33 ± 3.7	19-39	34.4 ± 1.7	32-38
Last Y-BOCS, mean score	17.2 ± 7.4	1-31	18 ± 3.2	11-21
Y-BOCS improvement, %	47.4 ± 21	10-97	47.2 ± 9.9	36-71
Responders, %	60.6 ± 36.2	0-100	70.7 ± 24.8	22-100
	Yes/no		Yes/no
RCT	6/23		1/10
Depression assessment	21/6		9/11
Depression improvement	15/4		8/1
Functionality assessment	16/13		7/4
Functionality improvement	14/1		7/0

DBS: Deep brain stimulation; NR: Not reported; RCT: Randomized controlled trial; Y-BOCS: Yale-Brown Obsessive Compulsive scale.

Table 4 Participant characteristics in the short-term studies

	Ref.	n	Female %	Average age (yr)	Average duration of illness (yr)	Average follow-up since DBS implantation (mo)	Target site
RCT	Abelson et al[67], 2005	4	50	40.2	22.5	12.8	ALIC
	Barcia et al[32], 2019	7	57.1	35.2	25.3	21	NAcc/CN
	Goodman et al[16], 2010	6	66	36.2	24	12	VC/VS
	Huff et al[31], 2010	10	40	36.3	22.2	12	NAcc
	Tyagi et al[17], 2019	6	16.6	45.5	24.1	12	VC/VS, STN, VC/VS/STN
	Welter et al[39], 2020	8	12.5	42.5	NR	22	STN, CN, NAcc
Non-RCT	Anderson and Ahmed[74], 2003	1	100	35	10	10	ALIC
	Aouizerate et al[75], 2009	2	0	51	33.5	15	NAcc/CN
	Azriel et al[76], 2020	1	100	67	44	16	amGPI
	Chabardes et al[29], 2020	19	63.1	39	20.7	24	STN
	Chang et al[77], 2017	1	100	28	8	12	VC/VS
	Coenen et al[79], 2017	2	0	41.5	29	12	MFB
	Denys et al[44], 2020	70	69	41.7	25	12	ALIC
	Doshi et al[80], 2019	1	100	42	NR	12	NAcc
	Farrand et al[42], 2018	7	57.1	46	25	31	NAcc or BNST
	Franzini et al[81], 2010	2	0	37	21.5	25.5	NAcc
	Gabriëls et al[53], 2003	3	67	41.7	24.3	27	NAcc/ALIC
	Grant et al[34], 2016	1	0	30	5	36	NAcc
	Huys et al[30], 2019	20	50	40.1	26.1	12	ALIC-NAcc
	Islam et al[40], 2015	8	17	45.8	30.2	25	BNST, NAcc
	Jiménez et al[55], 2013	6	50	34.7	16.2	24	ITP
	Maarouf et al[45], 2016	4	75	39.3	23.5	11.5	MD/VA
	Menchón et al[13], 2021	29	52	41	24.5	12	ALIC
	Mulders et al[82], 2017	1	100	49	34	24	VC/VS
	Plewnia et al[83], 2008	1	100	51	NR	24	ALIC/NAcc
	Roh et al[61], 2012	4	25	45.5	24.2	24	VC/VS
	Sachdev et al[84], 2012	1	100	32	28	7	NAcc
	Senova et al[85], 2020	1	100	72	52	36	STN
	Tsai et al[49], 2012	4	0	25.5	8.3	15	VC/VS

ALIC: Anterior limb on internal capsule; amGPI: Anteromedial globus pallidus internus; BNST: Bed nucleus of stria terminalis; CN: Caudate nucleus; ITP: Inferior thalamic peduncle; MD/VA: Medial dorsal and the ventral anterior nucleus of the thalamus; MFB: Medial forebrain bundle; NAcc: Nucleus accumbens; NR: Not reported; RCT: Randomized controlled trial; VC/VS: Ventral caudate/ventral striatum.

Table 5 Participant characteristics in the long-term studies

	Ref.	n	Female %	Average age (yr)	Average duration of illness (yr)	Average follow-up since DBS implantation (mo)	Target site
RCT	Luyten et al[20], 2016	24	50	39	NR	77	ALIC/BST
Non-RCT	Choudhury et al[78], 2017	1	100	45	21	51	ALIC
	Fayad et al[33], 2016	6	66	44.5	NR	92.5	VC/VS
	Graat et al[19], 2020	50	68	41.6	25.2	81.6	ALIC
	Gupta et al[35], 2019	2	100	46.5	23	42	VC/VS/ ALIC
	Greenberg et al[36], 2010	26	46	35.3	22	96	VC/VS
	Holland et al[21], 2020	9	44.4	40.2	NR	54.8	VC/VS
	Lee et al[37], 2019	5	60	32.4	16.2	49.8	ITP
	Mallet et al[22], 2019	14	42.8	43.8	NA	46	STN
	Polosan et al[38], 2019	12	67	38.3	18	38	STN
	Winter et al[28], 2021	6	33.3	39.6	18	72	ALIC/BNST

The study sample conducted by Fayad et al[33] corresponds to the follow-up of Goodman et al[16]’s study sample. Greenberg et al[36] conducted a multicenter study in which some patients from Fayad et al[33]’s study were included. The patients in the studies by Mallet et al[22] and Chabardes et al[29] are included in the STOC study. ALIC: Anterior limb on internal capsule; BNST: Bed nucleus of stria terminalis; ITP: Inferior thalamic peduncle; NR: Not reported; RCT: Randomized controlled trial; VC/VS: Ventral caudate/ventral striatum.

Table 6 Summary of results for the short-term studies

	Ref.	Average baseline Y-BOCS	Average Y-BOCS at LFU	Average Y-BOCS improvement (%)	Average responders (%)	Depression (HDRS, BDI, MADRS, DASS, POMS)	Depression scale improvement	Global functionality (GAF, CGIS, SOFAS)	Functionality improvement
RCT	Abelson et al[67], 2005	32.7	23	30	50	Yes, HDRS	Yes	NR	NR
	Barcia et al[32], 2019	32.2	15.4	51	85.7	Yes, HDRS and BDI	No	NR	NR
	Goodman et al[16], 2010	33.7	18	46	67	Yes, HDRS	Yes	Yes, CGISS	Yes
	Abelson et al[67], 2005	32.3	25.4	21	8.3	Yes, HDRS and BDI	Yes	Yes, GAF	Yes
	Barcia et al[32], 2019	36.1	14.1	61	NR	Yes, MADRS	Yes	NR	NR
	Goodman et al[16], 2010	33.5	23.2	30	37.5	Yes, MADRS	No	NR	NR
Non-RCT	Anderson and Ahmed[74], 2003	34	1	97	100	NR	NR	Yes, GAF	Yes
	Aouizerate et al[75], 2009	25	11	56	100	Yes, HDRS	Yes	NR	NR
	Azriel et al[76], 2020	33	16	48	100	NR	NR	NR	NR
	Chabardes et al[29], 2020	33.3	15.8	53	73	NR	NR	Yes, GAF	Yes
	Chang et al[77], 2017	36	25	30	0	Yes, HDRS	NR	Yes, GAF	Yes
	Coenen et al[79], 2017	30	20.5	31	50	Yes, BDI	Yes	Yes, GAF	NR
	Denys et al[44], 2020	33.7	20.2	40	52	Yes, HDRS	Yes	NR	NR
	Doshi et al[80], 2019	19	5	73.7	100	Yes, HDRS	Yes	NR	NR
	Farrand et al[42], 2018	32.8	24	26	42.8	Yes, DASS-D	Yes	Yes, SOFAS	Yes
	Franzini et al[81], 2010	34	20	41	50	Yes, HDRS	Yes	Yes, GAF	Yes
	Gabriëls et al[53], 2003	33.6	21	37.5	66.6	Yes, POMS	No	NR	NR
	Grant et al[34], 2016	32	9	71	100	NR	NR	NR	NR
	Huys et al[30], 2019	30.9	20.7	33	40	Yes, BDI	No	Yes, GAF	Yes
	Islam et al[40], 2015	35.3	20.8	41	50	Yes, HDRS	NR	Yes, GAF	NR
	Jiménez et al[55], 2013	35.8	15.5	56	100	NR	NR	Yes, GAF	Yes
	Maarouf et al[45], 2016	34.7	31	10	0	Yes, BDI	NR	Yes, GAF	No
	Menchón et al[13], 2021	34.7	20	42	60	Yes, MADRS	Yes	Yes, GAF	Yes
	Mulders et al[82], 2017	34	17	48	100	NR	NR	NR	NR
	Plewnia et al[83], 2008	31	24	25	0	NR	NR	Yes, GAF	Yes
	Roh et al[61], 2012	38	14.8	59.7	100	Yes, HDRS	NR	Yes, GAF	Yes
	Sachdev et al[84], 2012	39	5	87.1	100	NR	NR	NR	NR
	Senova et al[85], 2020	31	1	96	100	Yes, MADRS	Yes	NR	NR
	Tsai et al[49], 2012	36.3	24	33.8	25	Yes, HDRS	Yes	Yes, GAF	Yes

BDI: Beck depression inventory; CGISS: Clinical global impression severity scale; DASS-D: Depression anxiety stress scale-depression; GAF: Global Assessment of Functioning; HDRS: Hamilton depressive rating scale; LFU: Last follow-up; MADRS: Montgomery Asberg Depression rating scale; NR: Not reported; POMS: Profile of mood states; RCT: Randomized controlled trial; SOFAS: Social and Occupational Functioning Assessment scale; Y-BOCS: Yale-Brown Obsessive Compulsive scale.

Table 7 Summary of results for the long-term studies

	Ref.	Average baseline Y-BOCS	Average Y-BOCS at LFU	Average Y-BOCS improvement (%)	Average responders (%)	Depression (HDRS, BDI, MADRS, QIDS, IDS-30)	Depression scale improvement	Global buncionality (GAF, IADL, SF-36)	Functionality improvement
RCT	Luyten et al[20], 2016	35	19.3	45	67	Yes, HDRS	Yes	Yes, GAF	Yes
Non-RCT	Choudhury et al[78], 2017	37	21	43	100	Yes, BDI	Yes	Yes, IADL	Yes
	Fayad et al[33], 2016	33.6	15.1	55	66	Yes, HDRS	No	Yes, SF-36	Yes
	Graat et al[19], 2020	33.3	20.5	39	50	Yes, HDRS	Yes	Yes, GAF	Yes
	Gupta et al[35], 2019	38	11	71	100	Yes, BDI	Yes	NR	NR
	Greenberg et al[36], 2010	34	21.5	36	61	Yes, HDRS	Yes	Yes, GAF	Yes
	Holland et al[21], 2020	34.5	20.7	40.3	22	Yes, HDRS, MADRS, QIDS, IDS-30 and BDI	Yes	Yes, GAF	NR
	Lee et al[37], 2019	35	16	54	100	Yes, HDRS	Yes	NR	NR
	Mallet et al[22], 2019	32.4	15.4	50	75	Yes, BDI	Yes	Yes, GAF	Yes
	Polosan et al[38], 2019	34.3	20	41	NR	NR	NR	NR	NR
	Winter et al[28], 2021	32.1	17.7	45	66	Yes, BDI	Yes	NR	NR

BDI: Beck depression inventory; GAF: Global Assessment of Functioning; HDRS: Hamilton depressive rating scale; IADL: Lawton instrumental activities of daily living scale; IDS-30: Inventory of depressive symptomatology; LFU: Last follow-up; MADRS: Montgomery Asberg Depression rating scale; NR: Not reported; QIDS: Quick inventory of depressive symptomatology; RCT: Randomized controlled trial; SF-36: Short form survey; Y-BOCS: Yale-Brown Obsessive Compulsive scale.