Objectives
A correct switch between two antipsychotics, carried out to
overcome suboptimal efficacy or the onset of adverse effects of
a drug, is a relatively difficult task. The purpose of this review is
to present the main aspects that psychiatrists have to consider
planning a switch between antipsychotics. In particular, the issues
concerning the switch from first and second generation antypychotics
to asenapine, the latest second generation available
molecule, have been underlined.
Methods
A search on the main articles on the switch between antispychotics
published after 2005, and particularly in the last years,
was made on Pubmed and Medline. The most important studies
on pharmacodynamics and pharmacokinetics of antipsychotic
drugs have also been taken into account.
Results
The different pharmacodynamic properties of antipsychotics
depend on their affinities for receptors subclasses. In particular,
antipsychotic drugs with greater affinity for dopamine D2
receptors are generally more efficacious, but are also associated
with worse adverse effects (e.g. extrapiramidal symptoms
and hyperprolactinemia), at least if the action on D2 receptor
is not counterbalanced by a similar or superior action on effect
on serotonine 5HT2A receptor. Asenapine, however, has a
more affinity for 5HT2A receptor than for D2 receptor and this
may explain both these two receptorial subclasses and efficacy
on psychotic and maniacal symptoms and its fair tolerability;
furthermore, its low affinity for histaminergic and cholinergic receptors
is likely to be the reason for the low incidence of sedative
and anticholinergic effects.
The halflife of antipsychotic drugs is the most important pharmacokinetic
parameter to consider planning a switch. In fact,
the incidence of rebound effects is maximal when pre- and
post-switch drugs have markedly different pharmacodynamic
(i.e. receptorial affinity) or pharmacokinetic (i.e. halflife) characteristics.
This is particularly true when the pre-switch drug has
a short halflife, especially when switch is abrupt. Therefore, different
strategies to reduce the probability of the occurrence of
rebound effects have been described. For example, the switch
to asenapine, which has a relatively long halflife, from other
antipsychotics, should not be abrupt, but follow preferably a
“plateau cross-taper” mode.
Conclusions
A successful switch between antipsychotics depends on a wise
planning and knowledge of pharmacodynamic and pharmacokinetic
features of the involved drugs.
