Pharmacology of Atypical Antipsychotics
Atypical antipsychotics are used to treat schizophrenia, bipolar disorder and to treat severe psychomotor agitation. Here, we review the various medicines – their mechanism of action, side effects and drug interaction profiles.
Antipsychotics are typically divided into “typical” and “atypical antipsychotics”.
“Typical” antipsychotics are often classified as the first-generation, whereas atypical agents – the topic of this guide – are considered second-generation, though the merits of this distinction are now routinely called into question.
Typical antipsychotics include medicines such as haloperidol, chlorpromazine and prochlorperazine; drugs we review in another study guide.
Here, we review atypical antipsychotics – examples of which include:
Atypical antipsychotics are used to treat the following indications:
- Schizophrenia – where they are often used in cases where extrapyramidal side effects of first-generation agents have become intolerable.
- Bipolar disorder – most effective in acute episodes of mania or hypomania.
- Psychomotor agitation – where they act as calming, tranquilizing agents.
Some – such as quetiapine – may be used alongside other drugs in the treatment of major depressive disorder. In addition, some – such as risperidone and aripiprazole – are used to treat irritability in patients with autism.
Mechanism of action
Atypical antipsychotics work by blocking post-synaptic dopamine, D2 receptors.
More specifically, their antipsychotic effects are mostly mediated, it is currently believed, through D2 inhibition in the mesolimbic-mesocortical pathway.
One clear differentiation between first and second-generation agents is that extrapyramidal side effects are considerably more likely to occur in earlier, first-generation drugs than their second-generation, atypical cousins.
Extrapyramidal side effects include rigidity, dystonia, akathisia and, with long-term use, tardive dyskinesia.
This should not be taken as “atypicals do not cause extrapyramidal effects”, as that conclusion is wrong. Both classes cause extrapyramidal effects, but first-generation drugs cause these effects to a slightly greater degree.
Broadly speaking, side effects with atypical antipsychotics include – to varying degrees:
- Extrapyramidal effects – see above
- Metabolic effects – weight gain, diabetes, lipid alterations
- QT prolongation
Risperidone and olanzapine are associated with high prolactin levels – leading to breast effects and sexual dysfunction.
Clozapine is associated with agranulocytosis (in approx. 1 percent of patients).
When we talk about the clinical pharmacology of atypical antipsychotics, we need to think about the following factors:
- That because they prolong the QT interval, atypical antipsychotics should be avoided with other drugs that have the same effect – namely, SSRIs, fluoroquinolones, macrolides, amiodarone and quinine.
- That atypical antipsychotics should be avoided in patients with cardiovascular disease or in those with a history of neutropenia.
- That atypical antipsychotics should be avoided with dopamine-blocking drugs such as metoclopramide and domperidone (not available in US).
Atypical antipsychotics should be prescribed by a specialist; medicines that are used for the treatment of acute psychotic disease as well as the prevention of subsequent attacks.
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