Are there links between Alzheimer’s disease and ADHD? The efficacy of acetylcholinesterase inhibitors and NMDA receptor antagonists in controlling ADHD symptoms: a systematic review

Abdi Dezfouli, Ramin; Akbariforoud, Sara; Esmaeilidezfouli, Ensieh

doi:10.1186/s43045-024-00405-w

Middle East Current Psychiatry

Table 2 Summary result of clinical trials assessing the efficacy of anti-Alzheimer drugs in ADHD

From: Are there links between Alzheimer’s disease and ADHD? The efficacy of acetylcholinesterase inhibitors and NMDA receptor antagonists in controlling ADHD symptoms: a systematic review

Author, year	Final medication administration routine^a	Comparator arm	Other interventions	Trial duration	Result^b	Side effect	Tolerability^b
Memantine
Biederman et al. (2014) [46]	10-mg BID	Placebo	Adjunct to methylphenidate	14 weeks	Similar responses were seen for participants on placebo and memantine (SMD = − 0.29)	• 41.7% appetite decrease • 50% dry mouth • 50% headache	11.5%
Findling et al. (2007) [32]	10 mg/day	Pre- and posttreatment	-	8 weeks	Mean ADHD-IV total score change from baseline value was − 3.5 at week 4	• 25% nausea • 37.5% dizziness (only 20 mg/day group) • 25% headache	0%
Findling et al. (2007) [32]	20 mg/day	Pre- and posttreatment	-	8 weeks	Mean ADHD-IV total score change from baseline value was − 11.5 at week 4 and − 16.5 at week 8		0%
Riahi et al. (2020) [47]	0.1 to 0.25 mg/kg	Pre- and posttreatment	Adjunct to methylphenidate	8 weeks	The mean scores of the Conner’s score in both groups were significantly reduced. There was no significant difference between the two groups	• NR	12.8%
Riahi et al. (2020) [47]	0.25 to 0.5 mg/kg	Pre- and posttreatment	Adjunct to methylphenidate	8 weeks		• NR	12.8%
Mohammadi et al. (2015) [36]	10–20 mg/day	Methylphenidate 20–30 mg/day	-	6 weeks	A significant difference was observed at week 6 compared to baseline in both groups. There was not a significant difference between the two groups	• 22% loss of appetite • 31% irritability • 18% restlessness	-
Mohammadzadeh et al. (2019) [48]	20 mg/day	Placebo	-	6 weeks	There was a significant difference in the effect of drug and placebo changes	• NR	-
Surman et al. (2013) [35]	10-mg BID	Pre- and posttreatment	-	12 weeks	Each individual symptom of ADHD significantly improved	• 10% dizziness or lightheadedness, gastrointestinal, musculoskeletal, headache, and sedation	21.4%
Donepezil
Cubo et al. (2008) [37]	10 mg/day with a 4-week washout period	Pre- and posttreatment	-	18 weeks	There was no significant improvement in any mean measure of ADHD	• 20% irritability • 20% gastrointestinal symptoms • 5% headache, sedation, nightmares, urinary incontinence, and dizziness	50%
Doyle et al. (2006) [22]	Daily dose of 2.5 to 30 mg	Pre- and posttreatment	-	18 weeks	All but one participant showed improvement	No side effects were reported	12.5%
Wilens et al. (2000) [38]	20 mg daily	Pre- and posttreatment	Adjunct to methylphenidate	14 weeks	There was a significant effect of donepezil in improving ADHD symptoms	Only one patient developed diarrhea which resolved after dose adjustment	-
Wilens et al. (2005) [38]	10 mg daily	Pre- and posttreatment	Adjunct to methylphenidate	12 weeks	There were no clinically or statistically significant reductions in the rating-scale measures of ADHD	• 85% gastrointestinal problems • 46% irritability • 38% appetite loss	23%
Galantamine
Biederman et al. (2006) [40]	8–24 md daily	Placebo	-	12 weeks	There was no statistically or clinically significant greater reduction in either symptom cluster in the galantamine-treated patients relative to the placebo-treated subjects	• There were no differences between the galantamine- and placebo-treated subjects in the presence of any adverse effect	16%

^aOD Once daily, BD Twice a day, TDS Three times a day
^bDefined as percentage of patients who left the trial because of side effects

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