Antipsychotic

Two main types of antipsychotics are the typical antipsychotics and the atypical antipsychotics.

Antipsychotics are sometimes referred to as major tranquilizers, which is incorrect, as they have no relationship to the anti-anxiety benzodiazepines or any other relaxant drugs. Furthermore, although some antipsychotics do have a tranquilizing effect, others appear to reduce psychosis without tranquilizing the patient.

The drugs interact on a wide range of neuroreceptors[?] and often have antidopaminergic[?] effects, but appear primarily to block the dopamine receptors. The range of interactions produces many different adverse effects of extrapyramidal reactions, including acute dystonias[?], akathisia, rigidity and tremor, tardive dyskinesia[?], tachycardia, hypotension[?], impotence, lethargy, and seizures.

Some antipsychotics are:

• The Phenothiazines
  • chlorpromazine (Thorazine)
  • fluphenazine

• Haloperidol (Haldol)

They are believed to control the symptoms of schizophrenia by blocking dopamine receptors. However, there is generally a lag time of a few days to a few weeks between the time the drug is started and the time that the medication begins to reduce psychosis. Why this is so remains unclear.

Many of the drugs have serious side effects. One of the more serious is tardive dyskinesia, in which the drugs, when taken over the course of several years, cause permanent uncontrollable rhythmic motions in the limbs. However, the newer atypical antipsychotics such as clozapine do not appear to produce this side effect, and it is believed that the possibility of tardive dyskinesia can be reduced by combining the anti-psychotics with benedryl[?] or benztropine. Another serious side-effect is neuroleptic malignant symdrome, in which the drugs appear to cause the temperature regulation centers to fail, resulting in a medical emergency as the patient's temperature suddenly increases to dangerous levels.

Another problematic side-effect of antipsychotics is dysphoria[?], meaning that it just makes the patient feel bad. This side-effect is a major problem for patients with schizophrenia in that it causes them to discontinue medication, and this produces a relapse of psychotic symptoms. Much of the treatment of schizophrenia involves a trial-and-error search for medication that controls psychosis without making the patient dysphoric. Most of the drug research in antipsychotics involves finding new drugs to increase treatment options.

Drugs used as antipsychotics include the three groups of phenothiazines, thioxanthenes, diphenylbutylpiperidines, substituted benzamides, ioxapine (tricyclic dibenzoxazepine), clozapine (dibenzodiazepine) and oxypertine. All of the antipsychotics appear to work by blocking dopamine receptors. Antipsychotics are an area in which rationally designed drugs[?] is a useful strategy. Rather than attempting to use trial and error, drug manufacturers specifically design a molecule to fulfill a specific purpose, in this case blocking dopamine receptors.

The first antipsychotic was thorazine, which was developed as a surgical anesthetic. It was first used on mental patients in the belief that it would have a calming effect. However, the drug soon appeared to reduce psychosis beyond this calming effect, and it is now believed that the reduction of psychosis produced by the drug is unrelated to the calming effect of the medication.

Anti-psychotics can be classified on a spectrum of low potency to high potency, where potency refers to the ability of the drug to bind to dopamine receptors, and not to the effectiveness of the drug. High potency antipsychotics such as Haldol typically have doses of a few milligrams and cause less sleepiness and calming effects than low potency antipsychotics such as thorazine, which have dosages of several hundred milligrams.

Antipsychotics also can be classified as "typical" and "atypical." Typical antipsychotics include drugs which are related to those that have been used in clinical practice since the 1960s. Atypical antipsychotics, the first of which was clozapine, include a large number of new drugs which have entered practice since the 1990s. "Atypical antipsychotics" act on different neuroreceptors than typical antipsychotics, and have produced remarkable improvement in patients with which typical antipsychotics have not been of much benefit.

See also:

• Neuroleptic malignant syndrome

Extra notes.

The atypical antipsychotics appear to be as effective as the older phenothiazone[?] or Haloperidol drugs and have a much better side-effect profile, particularly in relation to extra-pyramidal side-effects.

They are much more expensive than the older drugs, but (at least in western society) there is little justification (if any) for using the older drugs. Quite massive weight gain is a problem with the new drugs, particularly Olanzapine and Clozapine.

Nevertheless, the new drugs are not a panacea, and medical science is a long way from curing the disease. Some 15% of patients don't respond (at least to the initial drug). Non-responders may be in a difficult situation because (at least in Australia) institutional support has been removed without being replaced with adequate relief of symptoms. Some non-responders will respond to other drugs but there is a significant unfortunate percentage that show no real response.

Benzodiazapines, while not curative, will often ameliorate some symptoms. Lithium and sodium valproate[?] may be useful drugs. There is some evidence that sodium valproate up-regulates Reelin. If true, this would be an exciting finding that might bring science closer to a real cure.