1. The Place of Memantine in the Treatment of Alzheimer’s Disease: a Number Needed to Treat Analysis Livingston G. and Kartona C. International Journal of Geriatric Psychiatry 2004; 19:919–925

2. Numbers Needed to Treat The NNT is the number of patients who need to be treated with the treatment in question, compared to another treatment (often placebo) for one patient to gain a specified benefit The NNT is a clinically useful measure of treatment effect NNTs depend on the definition of benefit

3. Numbers Needed to Treat: Calculation 1 NNT == 2 Definition of response e.g. Improvement and stabilisation on SIB scale Calculate % of patients under memantine and under placebo, e.g. 50% and 25% 50% – 25%

4. NNTs for AD Drugs Livingston and Katona used the NNT approach to define whether the effects of reported trials of AChE-I and of Memantine are clinically relevant Compared the NNTs for Memantine to the NNTs for Galantamine where there are the same or similar endpoints in terms of definitions of response Earlier analyzed NNTs of Donepezil and Rivastigmine are shown for comparison Livingston and Katona 2000 and 2004

5. CIBIC-Plus59 406 SIB38237 ADCS-ADL 19 34208 Responder (%)Responder (%)NNT Single domain Responder for Memantine Livingston and Katona 2004 OC analysis; Response = improvement or stabilization Reisberg et al., 2003 MemantinePlacebo

6. Other NNTs for Memantine Reisberg et al., 2003; EPAR 2000 LOCF analysis Responder (%)Responder (%)NNT MemantinePlacebo Improvement or stabilisation in 11618 CIBIC-Plus and SIB and ADL Improvement or stabilisation in 29106 CIBIC-Plus and SIB or ADL Improvement or stabilisation in 2167 CIBIC-Plus and SIB Improvement in 11211 CIBIC-Plus and SIB

7. BGP-D69 384 improvement  15% CGI-C77433 final score  4 Responder analysis64273 both above NNTs for Memantine in Severe Dementia Livingston and Katona 2004 OC analysis Winblad and Poritis 1999 Responder (%)Responder (%)NNT MemantinePlacebo

8. NNTs for Galantamine Livingston and Katona 2004Wilcock et al., 2000 Responder (%)Responder (%)NNT GalantaminePlacebo CIBIC-Plus62 509 no deterioration ADAS-cog63415 improvement  4

9. NNTs for Donepezil Livingston and Katona 2000Rogers et al., 1998 Responder (%)Responder (%)NNT DonepezilPlacebo ADAS-cog81585 no deterioration ADAS-cog53274 improvement ≥ 4 ADAS-cog 2586 improvement ≥ 7 CIBIC-Plus score25118 improvement ≥ 3 CIBIC-Plus score75555 deterioration ≥ 5

10. NNTs for Rivastigmine * Rosler et al., ** Corey-Bloom et al.Livingston and Katona 2000 Responder (%)Responder (%)NNT RivastigminePlacebo ADAS-cog improvement ≥ 4*241613 CIBIC-Plus improvement*37206 PDS (ADL) 291910 improvement  10%* ADAS-cog no deterioration**54274 CIBIC-Plus improvement**241612.5 PDS (ADL)251510 improvement  10%**

11. Conclusions Memantine: NNTs for memantine are comparable with NNTs of AChEIs Memantine is efficacious on cognitive and non cognitive domains Memantine treatment shows a clinically significant benefit in moderate to severe AD Livingston and Katona 2000 and 2004