| · General election
· EU services directive
· Repeat dispensing
· Community pharmacy
· New contract
· Charge refunds
· Technicians
· Antipsychotics
· Methadone
· The profession (2)
· Registration
Letters to the Editor
|
Antipsychotics
Atypicals have fewer side effects
From Mrs E. Brache, MRPharmS
I agree with Jonathan Bland that the typical antipsychotics should be
consigned to the pharmaceutical
dustbin (PJ, 26 March, p358), because
there is a new group of novel atypical antipsychotic agents with a distinctly
different mode of action to the current atypicals.
As Mr Bland correctly states, the “clinical trials for atypicals
use psychiatric rating scales to measure efficacy and outcome of treatment
and extrapyramidal side effects (EPSs)”. These outcome assessment
scales like Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric
Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI) are
important because, according to Stahl et al, positive symptom control
alone is an insufficient justification for using the older agents because
there is more to treating schizophrenia. Negative and cognitive symptoms
also need to be treated and typical antipsychotics may in fact worsen
negative symptoms.1
The older antipsychotics are effective in the treatment of positive symptoms
of schizophrenia, where the newer second generation novel agents improve
mood, cognitive and negative symptoms as well.1 This is due to their
5-hydroxy-tryptamine2A antagonism which, according to Stahl et
al, “in
the mesolimbic pathway does not interfere with antipsychotic actions,
in the nigrostriatal pathway reverses enough D2 blockade to reduce EPSs
and in the mesocortical pathway increases dopamine release enough to
improve cognition.”
All antipsychotics have dopamine D2 receptor blocking properties
which cause EPSs. Atypical antipsychotics have a lower risk of EPSs than
typical
antipsychotics because of their
5-HT2A receptor blocking action.1
The newer group of atypical antipsychotics agents are partial agonists
of D2 receptors, thereby “improving negative symptoms through alleviating
hypodopaminergic function in the prefrontal cortex”.2 Because of
their D2 partial agonism they do not cause increased prolactin levels.
Not only are they 5-HT2A receptor antagonists (so are all
the atypical antipsychotics) but also
5-HT1A partial agonists. This causes an “increase in dopaminergic
transmission in the striatum, thus decreasing EPSs”2 because
of the inhibitory actions on the serotonergic neurons. Because of their
5-HT1A partial agonism, prefrontal increases in dopamine and noradrenalin
are not blocked.1 Partial agonism at
5-HT1A receptor is associated with anxiolytic activity and is postulated
to reduce EPS risk.3
Aripiprazole, the first of the new atypical agents, compared favourably
to olanzapine in long-term studies (evaluating their efficacy and safety)
concerning weight gain and metabolic side effect profile.4,5
Factors to take into consideration when selecting an antipsychotic drug
include cost, which is usually increased by readmission to hospital due
to non-compliance with antipsychotic treatment because of the side effects
of the treatment. The side effects that play an important role are weight
gain, sexual dysfunction, metabolic abnormalities and sedation.
I suggest that patients are not cured by alleviating their positive symptoms
alone and as the newer atypical antipsychotics have fewer side effects
the reduction of absenteeism from the workplace is achieved more cost
effectively.
Elmarie Brache
Guernsey, Channel Islands
References
1. Stahl SM, Meltzer HY, Meyer JM, Kopala LC. Are
all antipsychotics equal for the treatment of cognition and effect
in schizophrenia?
2. Argo TR, Carnahan RM, Perry PJ. Aripiprazole, a novel atypical antipsychotic
drug. Pharmacotherapy 2004;24:212–28.
3. Deleon A, Patel NC, Crismon ML. Aripiprazole: a comprehensive review
of its pharmacology, clinical efficacy and tolerability. Clinical Therapeutics
2004;26:649–66.
4. Carson W, McQuade R et al. Long term weight effects of aripiprazole
and olanzapine: Results from a 26-week double-blind comparison study.
European Neuropsychopharmacology 2004;14(Suppl 3):S259.
5. Ray S, Correy-Lisle PK, Cislo PK, L’Italien G. Weiden P. An
economic evaluation of aripiprazole compared to olanzapine based on metabolic
side effect profile. European Neuropsychopharmacology, 2004;14 (Suppl
3):S279.
|
The
Pharmaceutical Journal