Typical and Atypical Antipsychotics

What differentiates atypical from typical antipsychotics?

Getty Images

Older antipsychotics are also known as first generation or typical antipsychotics. “Typical” refers to a few aspects characterizing these medications.

Mechanism of action

Typical antipsychotics block the neurochemical dopamine that has been traditionally considered to be the main culprit in schizophrenia. In pharmacological parlance, these effect is known as dopamine antagonism.

Side effects

Typical antipsychotics have been linked to a variety of neurological adverse effects ranging from muscular rigidity (parkinsonism), which can be seen early in the course of treatment to repetitive, involuntary movements, which tend to occur after taking these medications for a while (tardive dyskinesia).

In contrast, the newer antipsychotics are known as second generation or atypical antipsychotics. These second generations drugs were initially thought to be more effective and better tolerated by patients; thus, since they hit the market back in the early 1990s, they have been slowly replacing the older drugs as the treatment of choice for schizophrenia. It turns out that overall the second generation are not much more effective than the first generation and while better tolerated in some respects (less neurological adverse effects) they have their own set of problems (weight gain, increased blood sugar and cholesterol).

“Atypical” means that these medications are different with regards to:

Mechanism of action

The atypicals have a more transient dopamine antagonism than the typicals.  They also block serotonin, a second neurochemical that has been associated with schizophrenia and depression.

Side effects

Aypical antipsychotics are less prone to lead to either muscular rigidity (parkinsonism) or the delayed repetitive, involuntary movements (tardive dyskinesia).

What are the atypical antipsychotics?

  • Amisulpride (brand names:  Amazeo, Amipride, Amival, Solian Soltus, Sulpitac, Sulprix) (not available in the United States)
  • Aripiprazole (brand name: Abilify. Aripiprex)
  • Asenapine (brand names: Saphris, Sycrest) 
  • Blonanserin (brand names: Lonasen)  (only available in Japan and Korea)
  • Clozapine (brand names: Clozaril, FazaClo)
  • Iloperidone (brand names: Fanapt, Fanapta)
  • Lurasidone (brand names: Latuda)
  • Melperone (brand names: Bunil, Buronil, Eunerpan)(not available in the United States)
  • Olanzapine (brand names: Zyprexa, Zypadhera, Lanzek)
  • Olanzapine/Fluoxetine (brand names: Symbyax)
  • Paliperidone (brand names: Invega)
  • Quetiapine (brand names: Seroquel, Xeroquel, Ketipinor; Hedonin)
  • Risperidone (brand names: Risperdal)
  • Sertindole (brand names: Serdolect, Serlect)
  • Sulpiride (brand names: Dogmatil, Dolmatil, Eglonyl, Espiride, Modal, Sulpor (not available in the United States, Canada and Australia)
  • Ziprasidone (brand names: Geodon, Zeldox, Zipwell)
  • Zotepine (brand names: Losizopilon, Lodopin, Setous, Zoleptil) (not available in the USA, United Kingdom, Australia, Canada or New Zealand)

Are atypical antipsychotics better medications for schizophrenia than typical antipsychotics?

The jury is still out on this one.

With regard of how well they work for schizophrenia symptoms:

1. There are no clear differences between typicals and atypicals with regards to positive symptoms. Both categories of medications work reasonably well against positive symptoms.

2. There are no clear differences between typicals and atypicals with regards to improving negative symptoms. That being said typicals have a range of adverse effects including mental slowness and physical rigidity that may add to the negative symptoms. In other words typicals might make the negative symptoms worse. Atypicals, while not helping improve negative symptoms, do not make them worse.

It is important to be clear on this point as you may hear the claim that atypicals are better for negative symptoms. This claim is factually correct but it only means negative symptoms get worse with typicals but not with atypical neuroleptics.

3. There are also no clear differences between typicals and atypicals with regards to cognitive problems. However, as mentioned typicals have adverse effects such as mental slowness that may add to the cognitive symptoms. Similar to negative symptoms, typicals might make the cognitive symptoms worse, while atypicals, even if they do not improve negative symptoms, do not make them worse either.

It’ss worth making the same point as above one more time. You may hear the claim that atypicals are better for cognitive symptoms. Which claim is only correct when understood to mean that negative symptoms can get worse with typicals but not with atypical neuroleptics.

To summarize, the atypicals are as good as the typicals with regards to positive symptoms and they are not as bad as typicals with regards to worsening negative symptoms and cognitive deficits.

There is an exemption to the above rule. Clozapine, the first of the atypicals, is the only available medication for schizophrenia that improves positive, negative, as well as cognitive symptoms, all adding up to an overall improvement in the typical functional improvement that is the daily challenge most patient with schizophrenia face.

Continue Reading