Atypical Antipsychotics

What makes an antipsychotic atypical is not what it does, but what it doesn't do.  Historically, earlier antipsychotics like Haldol and Prolixin caused unwanted Parkinsons like problems, i.e. they caused muscle stiffness and other problems.  The atypicals do not usually cause these problems at therapeutic doses.  Unfortunately, these atypical agents do cause other problems including glucose and lipid elevations.

The following medicines are the typical Atypicals

Abilify, Geodon, Risperidone, Seroquel, Zyprexa

How do they work?

We don't know.  But there are some interesting concepts that we think are important.  We do know that all the atypicals have an effect on Dopamine, as did the typical antipsychotics before them.

If you think of electrical current and electrical outlets, then Dopamine circuits may be on overdrive in conditions like Schizophrenia.  The circuit is too strong.  Antipsychotics, both typical and atypical, have in common an action on Dopamine receptors, D2 type in particular.  They almost all weaken Dopamine circuits.

All except Abilify are antagonists at this Dopamine receptor.  And Abilify because it is a weaker stimulator of this receptor than Dopamine itself may be a kind of dampener too (to the extent that it keeps Dopamine ciruits weaker than they would be if it was not around).

Abilify has been used to help hard to treat depressed patients in combination with a traditional antidepressants.  Other atypicals have been used this way as well.

This Dopamine circuit may not only be relevant to why atypicals work, but also to why they don't usually have Parkinsonian side effects at therapeutic doses.

Think of two separate circuits in the brain.  Circuit One is linked to psychotic symptoms like hallucinations and delusions (mesolimbic and mesocortical Dopamine paths).  Circuit Two is linked to moving your limbs around (nigrostriatal Dopamine path).   The older agents like Haldol and Prolixin block both Circuit 1 and Circuit 2 at therapeutic dosages but the newer ones more selectively block Circuit 1 and spare Circuit 2.  So usually you feel better with less risk of movement problems.

There are other ways that atypical antipsychotics may help alleviate symptoms. 

I have kept this section brief.  These agents are new and much remains undiscovered.