by Nicole Evans M.D.

Created on: August 24, 2009

Antipsychotic medications are used primarily in psychotic states such as schizophrenia, delusional disorder, agitated manic episodes, and other hallucinatory states. The primary mechanism of action of antipsychotics is thought to be due to the blocking of dopamine receptors in the central nervous system.

Antipsychotics are generally grouped into the traditional (typical) and atypical antipsychotics. Traditional antipsychotics work by primarily blocking the D2 dopamine receptors. Atypical antipsychotics are considered to be atypical because they block D2 dopamine receptors as well as serotonin (5-HT) receptors.

An important difference between typical and atypical antipsychotics is the incidence of undesirable extrapyramidal side effects. Atypical antipsychotics have a much lower incidence of extrapyramidal side effects. These extrapyramidal side effects include:

-akathisia (motor restlessness)

-parkinsonism (bradykinetic rigidity, resting tremor)

-acute dystonic reactions (slow, prolonged muscle spasms of the tongue, neck and face, also called oculogyric crisis)

-tardive dyskinesia (repetitive, purposeless movement of the lips, tongue, eyes)

-neuroleptic malignant syndrome (treated with dantrolene)

An additional benefit of atypical antipsychotic medications is that they are more effective against the negative symptoms of schizophrenia, an area in which the traditional antipsychotic are minimally effective. The negative symptoms of schizophrenia include lack of ability to experience pleasure, lack of socialization, flat affect (lack of emotion), lack of motivation and poverty of speech. It

The efficacy with which atypical antipsychotics treat negative symptoms has been a significant advance in the treatment of schizophrenia. It is important to adequately treat the negative schizophrenic symptoms, which are thought to decrease quality of life more significantly than positive schizophrenic symptoms such as hallucinations and paranoia.

Traditional antipsychotic medications include:

Chlorpromazine (Thorazine)

Fluphenazine (Prolixin)

Trifluiperazine (Stelazine)

Thioridazine (Mellaril)

Perphenazine (Trilafon)

Haloperidol (Haldol)

Droperidol (Insapine)

Loxapine (Loxitane)

Thiothexene (Navane)

Haloperidol has uses other than as an antipsychotic. It is also used in the treatment of Tourette's syndrome, Huntington's disease and phencyclidine (PCP) overdose. Chlorpromazine is the prototypical antipsychotic and is also used to treat intractable hiccups. Thioridazine is rarely used due to its distinctive side effects including pigmentary retinopathy, cardiac arrhythmias and conduction block.

Atypical antipsychotic medications include:

Clozapine (Clozaril)

Risperidone (Risperdal)

Olanzapine (Zyprexa)

Clozapine can cause seizures and rarely causes agranulocytosis, a very serious condition. Weekly blood tests are required for patients on clozapine to monitor for agranulocytosis. Risperdone is a first-line agent for schizophrenia. This is because of its effectiveness against both positive and negative symptoms of schizophrenia. However, risperdone may cause prolonged QT intervals that lead to a propensity for potentially fatal heart arrhythmias in certain individuals.

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