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:

  • Clozapine
  • Aripiprazole
  • Olanzapine
  • Risperidone
  • Quetiapine
  • Ziprasidone

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.

Side effects

Broadly speaking, side effects with atypical antipsychotics include – to varying degrees:

  • Sedation
  • 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).

Clinical considerations

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.

For even more facts and pharmacology quiz questions on atypical antipsychotics pharmacology, register with PharmaFactz today. Check back to our pharmacy blog soon for even more great articles on other antipsychotic drug classes!