Table 2. An overview of the key features of the studies that have been included in the evaluation.

LMTM: leuco-methylthioninium bis-hydromethanesulfonate; MT: methylthioninium; MTC: methylthioninium chloride; ADAS-cog: Alzheimer’s Disease Assessment Scale-cognitive subscale; ADCS-ADL: Alzheimer’s Disease Co-operative Study-Activities of Daily Living; ADCS-CGIC: Alzheimer’s Disease Cooperative Study-Clinical Global Impression Change; WBV: whole brain volume; LVV: lateral ventricular volume; RCT: randomized controlled trial.

Sr #	Authors	Publication year	Age group	No. of patients	Study duration	Study type	Intervention group, medication's name, dosage, and administration method	Control (placebo) group, medication's name, dosage, and administration method	Outcome measures	Results
1	Schelter et al. [22]	2019	<90 years	1,162	First RCT = 15 months, second RCT = 18 months	Post hoc analysis of two phase III RCTs	Oral LMTM at 150 and 250  mg/day doses in the first RCT and LMTM 200 mg/day in the second RCT	Oral LMTM 8 mg/day	ADAS-cog 11, ADCS-ADL 23 scales, WBV, and LVV after 65 weeks	"Both monotherapy and add-on therapy result in extremely significant differences in cognitive decline and brain atrophy in patients with above-threshold plasma levels of MT. At 8 mg/day as monotherapy or as an adjunct to symptomatic therapies, hydromethylthionine shows pharmacological effects on brain structure and function. A plateau is observed at higher dosages, and higher dosage is consistent with the absence of dose-response observed in the phase III trials. The treatment benefit is expected to be greatest at 16 mg/day as monotherapy."
2	Wilcock et al. [23]	2018	<90 years	795	18 months	RCTs	The recommended dosage for LMTM used orally was 100 mg, to be taken twice a day	The dosage for oral LMTM was 4 mg administered either twice a day or once daily	The patients were seen once every 13 weeks, including the last session for therapy occurring at week 78 and the last safety check occurring at week 82 after they had stopped receiving treatment. These are the scales that were utilized: ADCS-CGIC, ADCS-ADL scale, ADAS-cog, and ADCS-cog	Patients who received LMTM as monotherapy at either of the two doses tested had constantly superior results than patients who got the same doses as an add-on to cholinesterase inhibitors and/or memantine. LMTM may be beneficial as single-agent therapy and 4 mg twice a day may be as effective as greater doses
3	Gauthier et al. [24]	2016	<90 years	891	15 months	RCTs	The prescribed dosage for LMTM was 75 mg administered twice a day as well as 125 mg administered twice daily	PO of 4 mg LMTM twice a day	ADAS-Cog, ADCS-ADL scale	The primary analysis for this study was negative, and the results do not suggest a benefit of LMTM as an add-on treatment for patients with mild-to-moderate AD
4	Baddeley et al. [25]	2015	___	321	24 months	RCTs	The dosages of oral MT administered were 69 mg/day, 138 mg/day, and 228 mg/day	___	ADAS-cog11, change in regional cerebral blood flow	At a minimal dose of 138 mg MT/day, a significant therapeutic benefit was shown on the ADAS-cog scale in moderate patients after 24 weeks and in both mild and moderate Alzheimer’s dementia after 50 weeks. However, at the same time points, the effect of 228 mg MT/day was less than that of 138 mg MT/day. After 20 weeks of therapy, a similar profile of drop in rCBF was observed in mild individuals. As a result, there was no dosage response relative to the nominal dose for any of these outcomes
5	Wischik et al. [26]	2015	N/A	321	Two years	RCTs	Oral MT 69, 138, and 228 mg three times a day	N/A	ADAS-cog11, change in regional cerebral blood flow	"At 24 weeks, there were vital treatment benefits in two distinct populations when the daily dose of 138 mg was used: in moderate subjects on the ADAS-cog scale and two other clinical scales." Both mild and moderate Alzheimer’s dementia showed improvement after 50 weeks of the ongoing treatment as measured by the ADAS-cog scale. Due to dose-dependent dissolution and absorption restrictions, the greatest dose administration was hampered. The daily minimal dose of safe and effective MT is 138 mg, which shows that further research on MT in AD is recommended
6	Wischik et al. [27]	2008	___	332	Over 50 weeks	RCTs	MTC oral at 30, 60,  and 100 mg three times a day	Placebo	ADAS-cog	At the 60 mg dose, MTC produced a significant improvement versus the placebo group. The overall effect size was -6.8 ADAS-cog units, compared to a fall of 7.8 units in the placebo group. MTC has shown great efficacy in mild and moderate AD