European College of Neuropsychopharmacology
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The 16th annual congress of the European College
of Neuropsychopharmacology was held in Prague from 20 to 24 September.
Lin-Nam Wang (on the staff of The Journal) reports
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Age and gender likely to impact upon the treatment of depression
Failure to pay attention to age and gender could confound predictions
of response to antidepressants, according to Professor Peter Joyce, department
of psychological medicine, University of Otago, New Zealand. Typical
predictors of response to treatment with an antidepressant include
the depressive symptoms suffered, the diagnosis, co-morbidities and
concurrent intake of drugs or alcohol (if more than four units per
day). However, perhaps it is time for age and gender to be considered,
Professor Joyce suggested as he went on to give an overview of studies
that have examined age and gender differences in treatment response
and tolerability.
Researchers found that when patients with major depression were randomly
assigned to 12 weeks of treatment with either imipramine or sertraline,
significantly more women responded to sertraline than to imipramine and
significantly more men responded to imipramine than to sertraline. Gender
and the drug a patient was randomised to take also influenced numbers
of drop outs from the trial, with women taking imipramine and men taking
sertraline more likely to drop out. These differences were not observed
in postmenopausal women, suggesting a hormonal link to responsiveness
and tolerability.
Fluoxetine is better tolerated in women than in men |
Similarly, a study led by Professor Joyce indicates that women are better
able to tolerate fluoxetine than nortryptiline and the converse applies
to men (Australian and New Zealand Journal of Psychiatry 2002;36:384–91).
Further research led by Professor Joyce (to be published) in which patients
were randomised to fluoxetine or nortryptiline, shows that 67 per cent
of those aged 18 to 24 years in the fluoxetine arm responded to treatment
but only 26 per cent in the nortryptiline arm responded. In comparison,
the proportions of responders in patients over 25 years, in both arms,
were closer. The study also suggested that clomipramine was better than
desipramine in patients under 25 years, but further trials are needed,
Professor Joyce said.
In addition, the study found that men aged over 40 years with melancholia
respond better to tricyclic antidepressants than selective serotonin
re-uptake inhibitors. In men, the density of 5-HT1A receptors in the
orbito-frontal cortex markedly decrease with age and Professor Joyce
suggested this as a possible explanation for the poorer response.
Gender, age and compliance
Professor Koen Demyttenaere, department of psychiatry, University Hospital
Gasthuisberg, Belgium, told the audience that age and gender were also
factors that could affect compliance with treatment. The most effective
way to see if patients are taking their medicines is to use technology
such as the Medication Event Monitoring System (MEMS). This uses microelectronic
technology in bottle caps to record each time a bottle is opened and,
if it can be assumed that every time a bottle is opened then a tablet
is taken, this gives a reliable measure of compliance.
Typically, a patient prescribed one tablet a day will take the tablet
promptly, (eg, at 7pm), for the first few days, but by days 10 to 20,
the patient will take the tablet a little earlier or a later, and after
day 20 doses might be missed. Factors influencing compliance include
drug regimen, age and gender, and Professor Demyttenaere highlighted
some of the evidence.
One study found that women achieve a greater percentage of days with
correct dosing than men (52 per cent compared with 33 per cent, P=0.02).
Also, simply asking patients to self-monitor their tablet taking (by
keeping a diary) increased compliance by about 10 per cent in both genders
(this was confirmed using MEMS). In another study, 270 patients diagnosed
with major depression were telephoned each month. Reasons for stopping
treatment included adverse effects, fear of drug dependence, lack of
efficacy and the patient’s belief that he or she had to get better
without drugs. The major reason (55 per cent), however, was feeling better.
Perhaps most interesting was that men tend to stop taking their medicine
as soon as they start to feel better but women continue.
In terms of age, it is a misconception that older patients are less compliant
and most studies find that non-compliance is higher in younger people.
Although non-compliance is always a problem in patients with depression,
most doctors only tackle compliance if a patient is not responding to
treatment. Doctors, Professor Demyttenaere said, have different reactions
towards non-compliance. One study, classed 59 per cent of doctors as “ego-defensive” (non-compliance
was the patient’s fault) and 10 per cent as “avoiding” (an
alternative treatment would be tried). Only 31 per cent were “task-oriented” and
tried to find the cause of non-compliance. Perhaps it is time to look
more at the interaction aspects of compliance and this means the relationships
between the physician, patient, partner and pharmacist, he said.
Speaking to The Journal after his presentation, Professor Demyttenaere
said: “There is good evidence of the educational role that pharmacists
can play, but they have to be careful — sometimes one word rather
than another can give the patient a negative impression”.
Using old drugs for new indications
Drugs approved for treating other diseases could play a role in strategies
to treat Alzheimer’s disease, Professor Konrad Beyreuther, centre
for molecular biology, University of Heidelberg, Germany, said during
the congress. Professor Beyreuther highlighted retrospective epidemiological
studies and experiments, which suggest that treatment with a cholesterol
lowering drug reduces production of abeta peptides that are the main component
of senile plaques.
Epidemiological studies indicate that treatment with statins reduces
the relative risk of Alzheimer’s disease by a factor of three. In
a 26-week, randomised controlled trial 44 patients with Alzheimer’s
disease were either given up to 80mg simvastatin daily or a placebo. Decreased
levels of abeta peptides were found in the cerebrospinal fluid of patients
with mild disease. Furthermore, disease progression in patients in the
treatment group was slower (indicated by mini-mental state examination)
but longer term and larger trials are needed, Professor Beyreuther said. |
