Efficacy of Ginkgo biloba extract EGb 761^® in dementia with behavioural and psychological symptoms: A systematic review

Figures & data

Table I. Characteristics of trial populations.

Clinical trial, author, date	Treatment groups	Randomized [N]	Drop-Outs [N] (%)^1	FAS [N]	Female [%]	Age [years] Mean (SD)
Nikolova et al. 2013	EGb 761^®	203	13 (6)	196	57	69 (8)
	Placebo	205	17 (8)	201	60	69 (8)
Napryeyenko and Borzenko 2007	EGb 761^®	200	4 (2)	198	72	65 (8)
	Placebo	200	5 (3)	197	72	63 (8)
Ihl et al. 2011a	EGb 761^®	206	16 (8)	202	69	65 (10)
	Placebo	204	12 (6)	202	66	65 (9)
Herrschaft et al. 2012	EGb 761^®	205	7 (3)	200	70	65 (9)
	Placebo	205	7 (3)	202	69	65 (9)
Total	EGb 761^®	814	40 (5)	796	67	66 (9)
	Placebo	814	41 (5))	802	68	66 (9)

¹Percent of randomized patients.

FAS, full analysis set (includes all patients valid for efficacy evaluation.

Table II. Baseline scores of clinical outcome measures [mean/(SD)].

Clinical trial	Treatment groups	N ^1	Cognition (SKT) [Mean (SD)] (range 0–27)	NPI total score [Mean (SD)] (range 0–144)	NPI Distress [Mean (SD)] (range 0–60)	ADL scale [Mean (SD)]	Global assessment [Mean (SD)]	Quality of Life [Mean (SD)]
						GBS-ADL (Range 0–36)	GBS-total score (Range 0–126)
Nikolova 2013	EGb 761^®	196	14.9 (4.3)	17.1 (9.5)	10.1 (6.4)	2.3 (3.4)	26.0 (13.1)	–
	Placebo	201	15.4 (4.2)	16.9 (8.7)	9.5 (5.2)	2.6 (3.6)	26.7 (12.7)	–
						GBS-ADL	GBS-total score
Napryeyenko and Borzenko 2007	EGb 761^®	198	15.6 (3.9)	21.3 (9.5)	13.5 (6.7)	4.8 (3.9)	35.3 (9.1)	–
	Placebo	197	15.4 (3.7)	21.6 (9.9)	13.4 (6.4)	4.9 (4.1)	34.3 (8.7)	–
						ADL-IS (Range 0–4)	ADCS-CGIC	(DEMQOL- PROXY) Range(31–124)
Ihl et al. 2011a	EGb 761^®	202	16.7 (3.9)	16.4 (8.1)	9.6 (5.6)	1.9 (0.6)	–	87.9 (11.7)
	Placebo	202	17.2 (3.7)	17.0 (8.2)	10.0 (5.4)	2.0 (0.5)	–	88.0 (10.9)
						ADL-IS	ADCS-CGIC	(DEMQOL- PROXY)
Herrschaft et al. 2012	EGb 761^®	200	15.1 (4.1)	16.8 (6.9)	10.2 (5.3)	1.7 (0.6)	–	85.7 (10.6)
	Placebo	202	15.3 (4.2)	16.7 (6.4)	10.1 (5.1)	1.8 (0.6)	–	86.0 (10.3)

¹N includes all patients valid for evaluation of efficacy (FAS).

Figure 1. Changes of SKT total scores based on the full analysis set (FAS).

Figure 2. Changes of NPI total scores [A] and caregiver distress scores [B] based on the full analysis set (FAS).

Figure 3. Changes of ADL scores (GBS-ADL, ADL-IS) based on the full analysis set (FAS).

Figure 4. Clinical global assessment (change scores of GBS-total score, ADCS-CGIC) based on the full analysis set (FAS).

Figure 5. Changes of DEMQOL-PROXY total score based on the full analysis set (FAS).

Table III. Aggregated outcomes for diagnostic subgroups; mean changes from baseline with standard deviations; LS mean differences (SKT, NPI, DEMQOL-Proxy), standardised LS mean differences (GBS-ADL, ADL-IS) or standardised mean differences (GBS total score, ADCS-CGIC) and 95% confidence intervals.

Outcome measure/ Subgroup	EGb 761^®N/ Mean/SD			Placebo N/Mean/SD			(Standardised) (LS) mean difference/95% CI
SKT total score
Probable AD	279	–1.86	3.11	281	–0.41	3.41	–1.50	[–2.03;–0.98]
Probable VaD	188	–2.42	2.79	186	0.07	3.18	–2.60	[–3.20;–2.00]
Mixed type	329	–2.52	3.35	335	–0.16	3.69	–2.35	[–2.88;–1.82]
NPI total score
Probable AD	279	–4.50	6.62	281	–0.65	7.32	–3.72	[–4.81;–2.62]
Probable VaD	188	–5.01	6.64	186	–0.27	6.85	–4.84	[–6.21;–3.46]
Mixed type	329	–4.26	6.47	335	–1.00	6.66	–3.37	[–4.34;–2.39]
NPI caregiver distress score
Probable AD	279	–2.20	4.30	281	–0.32	4.43	–1.84	[–2.52;–1.17]
Probable VaD	188	–3.57	4.52	186	–0.12	3.86	–3.36	[–4.19;–2.54]
Mixed type	329	–2.48	4.44	335	–0.45	3.63	–2.11	[–2.68;–1.53]
ADL score
Probable AD	279	–0.05	1.35	281	0.22	1.31	–0.35	[–0.51;–0.19]
Probable VaD	188	–1.21	2.37	186	0.49	2.36	–0.80	[–1.02;–0.57]
Mixed type	329	–0.58	1.86	335	0.26	1.52	–0.61	[–0.75;–0.46]
Clinical Global Assessment
Probable AD	278	1.07	5.97	278	2.73	5.59	–0.52	[–0.69;–0.36]
Probable VaD	188	–4.79	9.18	184	3.12	7.27	–1.08	[–1.30;–0.86]
Mixed type	327	–1.12	8.10	335	2.97	5.43	–0.77	[–0.92;–0.61]
DEMQOL-Proxy
Probable AD	171	3.40	8.83	158	0.27	7.00	2.40	[0.85;3.95]
Probable VaD	59	3.31	9.17	54	2.63	7.65	0.74	[–2.17;3.64]
Mixed type	172	3.48	8.60	192	2.06	8.05	1.90	[0.36;3.44]

Table IV. Summary of results of the responder analysis.

Response	Trials	N	Difference of response rates and 95% CI			NNT and 95% CI
Improvement SKT ≥ 3 points	4	1589	0.25	[0.21;	0.29]	4	[4;	5]
Improvement NPI total score ≥ 4 points	4	1589	0.28	[0.24;	0.33]	4	[4;	5]
Improvement GBS-ADL	2	792	0.24	[0.18;	0.30]	5	[4;	6]
Improvement ADL-IS	2	806	0.28	[0.22;	0.35]	4	[3;	5]
Improvement GBS total score ≥ 8	2	792	0.32	[0.27;	0.38]	4	[3;	4]
Improvement ADCS-CGIC	2	806	0.30	[0.23;	0.36]	4	[3;	5]

N, total number of patients included in the meta-analysis; CI, confidence interval; NNT, number needed to treat.

Table V. Numbers of serious adverse events under EGb 761^® and placebo treatment, respectively.

Event	EGb 761^® (n = 814)	Placebo (n = 814)
Angina pectoris	6	11
Arrhythmia	1	0
Acute cardiac failure	1	0
Caridac arrest	1	0
Hemiparesis	1	1
Hypoesthesia	0	1
Aphasia	0	1
Vertebrobasilar insufficiency	1	0
Cerebrovascular accident	1	0
Transitory ischaemic attack	1	0
Ischaemic stroke	1	1
Haemorrhagic stroke	0	1
Vascular encephalopathy	0	1
Head injury	0	1
Agitation	0	1
Pneumonia	0	2
Viral infection	1	0
Erosive gastritis	1	0
Femur fracture	0	1
Breast cancer	1	0
Lung cancer	1	0

Nikolova G, Yancheva S, Raychev I, Hoerr R, for the PLAGIN Study Group. 2013. Ginkgo biloba extract in dementia: A 22-week randomised, placebo-controlled, double-blind trial. Bulgarian Neurology 14:139–143.

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Napryeyenko O, Borzenko I, GINDEM-NP Study Group. 2007. Ginkgo biloba special extract in dementia with neuropsychiatric features. A randomised, placebo-controlled, double-blind clinical trial. Arzneimittelforschung 57:4–11.

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Ihl R, Bachinskaya N, Korczyn A, Vakhapova V, Tribanek M, Hoerr R, et al. 2011a. Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features. A randomized controlled trial. Int J Geriatr Psychiatry 26:1186–1194.

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Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. 2012. Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res. 46:716–723.

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