Narcissus and Daffodil

362 D. Brown
statistically significant improvements in non-standard neuropsychological tests of
verbal, non-verbal, language, motor or attention functions at 2 months, nor at
6 months in ten patients still receiving the drug. At 12 months, six patients still
taking galanthamine showed positive changes in everyday function and/or emotional
stability, as noted by their carers. These patients appeared to deteriorate during
drug withdrawal periods of unspecified length. No adverse events were reported.
This pilot study suggested that there may be a sub-group of AD patients responding
to galanthamine, whose pathology had a major component of cholinergic deficit.
In an effort to determine any relationship between dose and clinical benefit,
Wilcock et al. (1993) treated 19 probable AD patients (as defined by NINCDS
criteria) with either low dose (30–40 mg) or high dose (45–60 mg) daily doses of
galanthamine for two, six-week periods, separated by a three-week washout. Seven
patients withdrew due to unacceptable side effects (mainly gastrointestinal, in the
high-dose group) leaving 12 evaluable patients: five males with a mean age of 58
years (range 48–74 years) and seven females of mean age 67 years (range 55–79
years). Patients were assessed by a battery of recognised tests of neuropsychological
and mental function, including the MMSE and the Alzheimer’s Disease Assessment
Scale (ADAS, or if referring to the cognitive section alone, then ADAS-Cog,
after Rosen et al. (1984); see Table 14.1). While a trend towards improvement was
observed in several of these tests which, curiously, was most marked during the
lower rather than higher dose regimen, the sole statistically significant change was
an improvement in the cognitive component of the ADAS. Some deterioration was
seen during the washout phase. A clinical, but statistically insignificant, improvement
was recorded in the MMSE during the low-dose regimen; no clinically or
statistically significant changes were observed in the Functional Life Scale, the
Digit Span test or the Relatives’ Stress Scale. Four patients extended from the
trial on galanthamine remained stable for 12 months; three others were stable for
9months.
These early pilot studies do provide an impression of benefit for galanthamine
in AD; however, larger clinical trials were clearly needed to examine issues such as
what dose to use in relation to disease severity, duration of therapy and medium to
long-term side effect profile.
Later clinical trials
As with earlier work, interpretation of the results is made difficult by the
nature of the publications. Most trials are reported in abstracts of symposium
proceedings and, while the most important information is present, qualifying
data on side effects, withdrawals, dose adjustments and assessment techniques
are lacking.
Rainer et al. (1994) recruited 58 patients with AD who were treated with galanthamine,
20–50 mg daily for 3 weeks, during a single-blind preliminary investigation
to find galanthamine responders for entry in a subsequent placebo-controlled
trial. Galanthamine produced a mean decline (which represents a favourable
effect) in the ADAS-Cog of 4.21 (from 32.72 to 28.51), while the MMSE score
increased to 20.15 from 18.65 (a favourable result, indicating improvement in
cognitive function). As with any such short-term open study, improvement might
have been a practice, rather than a drug effect.