Narcissus and Daffodil

364 D. Brown
( Jann, 1998); see Table 14.1). Adverse events were recorded and haematological and
biochemical parameters were monitored. Patients were assessed at baseline and at
6 and 12 weeks during treatment. An analysis of patients remaining in the trial at
12 weeks showed that the cognitive performance of placebo-treated patients had
deteriorated during the treatment phase, but this was attenuated in all the
galanthamine groups, with mean ADAS-Cog scores one or two points greater than
zero. A trend in relationship to dose was apparent, although no statistical analysis
of this was reported. The differences between the placebo and active scores for the
30 mg and 45 mg/day groups were 3.8 and 3.9 points, respectively. Positive trends
on the CIBIC Plus scale were also associated with galanthamine. On an intentionto-treat
basis, the 30 mg/day dosage produced a statistically significant rise in
ADAS-Cog score of 3.4 points from placebo. Side effects were mostly related to the
cholinergic action of the drug, and occurred during the initial dose adjustment
phase. The incidence of nausea was 0, 13, 18 and 35% in the placebo, 22.5, 30 and
45 mg/day groups, respectively; the corresponding incidences for vomiting were 6,
19, 7 and 17%, respectively. Overall, galanthamine was described as being well
tolerated, although 38% of patients in the 45 mg/day regimen (compared with 8,
19 and 12% of patients taking placebo, 22.5 mg or 30 mg doses, respectively) withdrew
due to cholinergic side effects, mainly during the dose-escalation phase. This
is an indication of the likely maximum dose at which galanthamine may be tolerated
or, at least, a warning that if such high doses are to be used, a more cautious
dose escalation technique should be employed. No abnormalities in liver function
tests were observed. The authors concluded that patients received optimal benefit
from 30 mg/day, and that a longer titration period to achieve this dosage might
avoid the cholinergic symptoms of more rapid initiation.
Wesnes et al. (1998) published a brief report focusing on the effect that galanthamine
might have on the attention deficit seen in AD patients. They described a
double-blind, parallel group trial in 30 patients randomised to receive either 30 or
40 mg/day of galanthamine for 12 weeks, following a dose titration period of 4
weeks. Attention deficit was measured using an attentional sub-battery of tests of
cognition. No statistical analysis was reported, but improvements described as
significant were observed in all three attention tests used, starting early on in
therapy, increasing with time, but which rapidly declined on stopping galanthamine.
The attention tests used in this trial were not part of the more usual
ADAS-Cog test battery, and the authors pointed out that the tests they used may
provide important additional information on the use of drugs for AD.
Longitudinal studies
Patients with AH may live for many years and clearly, the long-term efficacy and
safety of a therapeutic agent used in the disease is of great importance. As yet, few
data are available for galanthamine. Recently, the interim results from an open,
3-year follow-up evaluation of patients using galanthamine have been published
(Rainer and Mucke, 1996). Patients receiving galanthamine with or without additional
non-anticholineterase therapy (data reported on 21), such as antidepressants
and nootropics, showed a significantly lower rate of cognitive decline than
those taking placebo (data reported on 23), as shown by the mean ADAS-Cog
scores. The degree of cognitive stabilisation achieved during the first year was a