Pharmacodynamic and pharmacokinetic principles of optimal switch between antipsychotics: focus on asenapine

Principi farmacodinamici e farmacocinetici dello switch ottimale tra antipsicotici: focus su asenapina

U. Albert1, E. Spina2

1 Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Italy; 2 Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Messina


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.


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.


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.


A successful switch between antipsychotics depends on a wise planning and knowledge of pharmacodynamic and pharmacokinetic features of the involved drugs.

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