Narcissus and Daffodil

No significant
correlation
between dose
and cognitive
improvement
Nausea and vomiting
dose-related: mean
dose 29.4 mg: 21%; 34.7
mg: 29%; 37.9 mg: 63%.
Diarrhoea, 4%; abdominal
cramps, 4%, weight
loss, 1.2%, anorexia,
3%. 78% tolerated individual
best dose
Mean improvement in ADAS-
Cog of 5.14, MMSE 1.72 after 3
weeks dose adjustment phase. At
13 weeks, further improvement
(1.7 points) in ADAS-Cog.
Patients taking placebo deteriorated
by 1.4 points. MMSE
improved by 1.7 at 3 weeks and
2.5 at 13 weeks; placebo score
dropped 1.7 points below baseline.
Changes in CGIC described
Initial 3-week
dose titration
phase, then
20–50 mg best
dose or placebo
for 10 weeks
Multicentre.
Randomised,
double-blind,
placebo
controlled
after initial
recruitment
of responders.
MMSE
ADAS-Cog
CGIC
141 with mild/
moderate,
probable AD
(NINCDS)
International
Berzewski
et al.,
1994
Pilot study.
Number of patients
on which analyses
based unspecified
Nausea and vomiting at
start of therapy. Light
headedness, agitation
and sleep disturbance.
Blood chemistry
normal
as favourable on galanthamine
Mean improvement in ADAS-
Cog of 1.33 with galanthamine
and deterioration of 0.81 points
with placebo. Results not statistically
significant. Significant
improvement in physicians global
evaluation on galanthamine
20–50 mg for
10 weeks
Multicentre.
Double-blind,
placebo
controlled.
ADAS-Cog
Germany 95 (60–87 years)
with mild/moderate
primary degenerative
dementia;
recruited after a
positive initial response
under single
blind conditions
England 235 with mild/
moderate AD
(NINCDS)
Kewitz
et al.,
1994
Interim report of
on-going trial.
Some evidence of
dose-response
correlation.
Authors suggest
that 30 mg/day may
be the optimum, to
balance side effects
with efficacy
Incidence of nausea
dose-related: 0, 13, 18,
35% in placebo, 22.5,
30.0 and 45.0 mg
galanthamine groups.
The groups had 8, 19,
12 and 38% withdrawals
respectively. Adverse
events occurred mainly
during dose escalation.
No changes in liver
In patients remaining at 12
weeks, galanthamine attenuated
decline in ADAS-Cog at all 3
doses. In the 30 mg/day group,
difference from placebo
(3.4 points) statistically, highly
significant, on intention
to treat basis. Positive trends in
CIBIC Plus also observed
22.5, 30.0 or
45.0 mg for
10 weeks
Randomised,
double-blind,
placebo
controlled
after initial
1/2 week dose
adjustment.
ADAS-Cog
CIBIC Plus
Wilcock
and
Wilkinson,
1997
function tests
Not reported Pilot study.
Improvements
reversed on
stopping drug.
No statistical tests
reported
‘Significant’ improvement in
attentional tasks starting as
early as 2 weeks
After 4-week dose
titration, either 30
or 40 mg for 12
weeks
Randomised,
double-blind,
parallel group.
Battery of
attentional tests
England 30 with AD
(diagnostic
criteria not
reported)
Wesnes
et al.,
1998
Notes
a
ADAS-Cog: Alzheimer’s Disease Assessment Scale – Cognitive Subscale (a positive number indicates decline and a negative number, improvement); CIBIC Plus:
Clinician Interview Based Impression of Change; CGIC: Clinical Global Impression of Change; MMSE: Mini-Mental State Examination.