Antipsychotic

The term antipsychotic is used for any drug used to control the acute symptoms of schizophrenia, they are also used to prevent relapses and to diminish chronic symptoms. They can also combat the problems of mania. They are sometimes incorrectly 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 tranqulizing the patient.

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

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 cogentin or benedryl. 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 makes the patient just 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 feel awful. 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 specificly design a molecule to fulfil 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 on 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 antopsychotics include drugs which are related to those that have been used in clinical practice since the 1960's. Atypical antipsychotics, the first of which was clozapine, include a large number of new ones have entered practice since the 1990's. "Atypical antipsychotics" act on different neuroreceptors than the typical antipsychotics and have produced remarkable improvement in patients with which typical antipsychotics have not been of much benefit.

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Extra notes.

The atypical antipsychotic appear to be as effective as the older phenothiazone or Haloperidol drugs and have a much better side-effect protocol especially with 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 Olazapine and Clozapine.

Having said this, the new drugs are not a panacea and we are a long way from curing the disease. Some 15% of patients dont respond (at least to the initial drug). I feel non-responders are in difficult situation because (at least in Australia) we have taken away their institutional support but we have not 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 us closer to a real cure.