Medications
Atypical (second generation) Antipsychotics
Definition and Characteristics
Atypical Antipsychotics are also referred to as second generation antipsychotic medication. Strictly speaking they are a group of newer medications that share the following features:
-
They are less likely to cause acute and chronic EPSE (extrapyramidal side effects). -
They are less likely to cause sustained increases in levels of the hormone prolactin.
-
They may be better at targeting the negative symptoms of schizophrenia.
-
They may offer some advantage over older drugs in treating refractory patients.
Atypical antipsychotic medications are less likely to produce TD (Tardive Dyskinesia). They may be associated with other significant metabolic side effects, including insulin resistance (hyperglycemia and Type II diabetes). Clozapine and olanzapine present the greatest risks of insulin sensitivity and weight gain. Risperidone and quetiapine are next. Ziprasidone and aripiprazole represent the lowest risk.
Drug-naïve (people with schizophrenia who have never received antipsychotics) have an increased risk of abnormal glucose metabolism (hyperglycemia). Weight gain plays a direct role in the risk of Type II diabetes.
Indications
Atypical antipsychotics are indicated for the treatment of schizophrenia. Some have FDA (Food and Drug Association) approval for other indications, including acute mania, bipolar mania, bipolar maintenance, psychotic agitation, as well as Tourettes’s Syndrome and Autism.
Drugs and Availability
Atypical antipsychotic medications approved by the FDA for the treatment of Schizophrenia include, in the order that they were marketed in the United States:
-
clozapine (Clozaril) (1990)
-
risperidone (Risperdal) (1993)
-
olanzapine (Zyprexa) (1996)
-
quetiapine (Seroquel) (1997)
-
ziprasidone (Geodon) (2001)
-
aripiprazole (Abilify) (2002)
-
paliperidone (Invega) (2006)
The drugs sertindol (Serlect and Serdotect), zotepine (Nipolept), and amisulpride (Solian) are not approved by the FDA (Food and Drug Administration) for use in the United States.
Treatment Goals
The goals of treatment with any antipsychotic medications are to relieve positive symptoms, to improve how the patient feels, to delay or prevent relapse, and to minimize side effects. Relapse is common when medications are discontinued, especially when they are discontinued abruptly. The first step in minimizing side effects is to use the lowest effect dose. The particular agent selected may also have a dramatic effect.
Mechanism of Action
While the precise mechanism of action of all antipsychotic medications is unknown, it is believed that it involves control of the neurotransmitter dopamine by influencing the levels of this chemical or effects on its receptors. In order to provide antipsychotic effects, a drug must alter dopamine levels or binding.
The neurotransmitter serotonin may also play a critical role. D2 receptor and serotonin antagonism may be involved. The binding characteristics for these two neurotransmitters varies greatly between atypical agents. This variability may be responsible for the atypical characteristics themselves, as well as the clinical differences between these agents; including the patient’s response and the side effect profiles.
History
Atypical antipsychotics have replaced typical, or first generation antipsychotics, as the first-line treatment for Schizophrenia.
Clozapine was the first of these agents. It was discovered in the 1950s and marketed in the 1970s, but was removed from the market due to agranulocytosis. It reemerged after it was shown to be effective in refractory (treatment resistant) patients with schizophrenia and adverse-event-monitoring (the weekly monitoring of white blood cell counts) became available.
In the 1990s, olanzapine, risperidone and quetiapine entered the marketplace. Ziprasidone and aripiprazole followed in the early years of this century.
Paliperidone became available in late 2006.
(Sources: The author’s knowledge base, unless otherwise noted.)
______________________________________________________________________
Related Articles:
______________________________________________________________________
