Antipsychotic

The term antipsychotic is applied to a group of drugs used to treat psychosis. Common conditions with which antipsychotics might be used include schizophrenia, mania and delusional disorder, although antipsychotics might be used to counter psychosis associated with a wide range of other diagnoses. Antipsychotics also have some effects as mood stabilizers, leading to their occasional use in treating mood disorder (particularly bipolar disorder) even when no signs of psychosis are present. Some antipsychotics (haloperidol, pimozide) are used to treat Tourette's Syndrome.

These drugs are also referred to as neuroleptic drugs, or simply neuroleptics.

There are currently two main types of antipsychotics in use, the typical antipsychotics and atypical antipsychotics. A new class of antipsychotic drugs has recently been discovered, known as partial dopamine agonists. Clinical development has progressed rapidly on partial dopamine agonists, and one drug in this class (aripiprazole) has already been approved by the FDA. Although the underlying mechanism of this new class is different from all previous typical and atypical antipsychotics, partial dopamine agonists are often categorized as atypicals.

Typical antipsychotics are sometimes referred to as major tranquilizers because some of them can tranquilise and sedate when taken in large doses. This term is increasingly disused because many antipsychotics do not have strong sedating properties and the terminology implies a connection with benzodiazepines whereas none exists.

Contents

Common antipsychotic drugs

Commonly used antipsychotic medications are listed below by drug group. Trade names appear in brackets.

  • Atypical antipsychotics
    • clozapine (Clozaril)- Requires weekly to every two week CBC (FBC) due to risk of decreased WBC.
    • olanzapine (Zyprexa) - Used to treate psychotic disorders including acute manic episodes and maintenance of bipolar disorder. Dosing 2.5 mg to 20 mg per day. Comes in a form that quickly dissovles in the mouth (Zyprexa Zydis). May cause appetite increase, weight gain, altered glucose metabolism; increased risk of diabetes mellitus.
    • risperidone (Risperdal) - Dosing 0.25 - 6 mg per day and is titrated upward; divided dosing until initial titration is completed, then can be once daily. Available in long-acting form (Risperdal Consta that is administered every 2 weeks; usual dose is 25 mg.). Comes in a form that quickly dissovles in the mouth (Risperdal M-Tab)
    • quetiapine (Seroquel)- Also used to treat bipolar disorders; helps with sleep (if used for sleep and not effective at 200 mg, it is not going to be effective in this regard) Dosing 25 mg up to 800 mg maximum. Usually see smaller doses during the day and larger dose at bedtime.
    • ziprasidone (Geodon) - Now approved to treat bipolar disorder. Dosing 20 mg twice daily initially up to 80 mg twice daily. Prolonged QT interval a concern; watch closely with patients who have heart disease; when used with other drugs that prolong QT interval potentially life-threatening.

Symbyax - (combination of Zyprexa and Prozac used in the treatment of bipolar depression.

  • Tetrabenazine (Nitoman® in Canada and Xenazine® in New Zeland and some parts of Europe) is similar in function to antipsychotic drugs, though isn't generally considered an antipsychotic itself. This is likely due to it's main usefulness being the treatment of hyperkinetic movement disorders such as Huntington's Disease and Tourette's Syndrome, rather than for conditions such as schizophrenia. Also, rather than having the to potential to cause tardive dyskinesia that most antipsychotics have, tetrabenazine can actually be an effective treatment for the condition.

The typical antipsychotic drugs are now out of patent meaning any pharmaceutical company is legally allowed to produce cheap generic versions of these medications. Whilst this makes them a great deal cheaper than the atypical drugs which are still in patent, atypical drugs are preferred as a first line treatment due to the fact that they generally have fewer side effects and seem to have additional benefits for the 'negative symptoms' of schizophrenia, a typical condition for which they might be prescribed.

Drug action and effectiveness

All antipsychotic drugs tend to block the D2 neuroreceptors in the dopamine pathways in the brain, so the normal effect of dopamine release in the relevant synapses is reduced.

It is the blockade of D2 receptors in the mesolimbic pathway of the brain which is thought to produce the intended antipsychotic effect.

Typical antipsychotics are not particularly selective and also block the same receptors in the mesocortical pathway, tuberoinfundibular pathway and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects that the typical antipsychotics can produce (see below).

Atypical antipsychotic drugs have a similar blocking effect on D2 receptors but seem to be a little more selective, targeting the intended pathway to a larger degree than the others. They also block or partially block serotonin receptors (particularly 5HT2A,C and 5HT1A receptors).

This combination of effects on both dopamine and serotonin receptors might be why atypical antipsychotic drugs tend to have fewer side effects than typicals and have a seemingly additional effect on the 'negative symptoms' of schizophrenia.

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 haloperidol typically have doses of a few milligrams and cause less sleepiness and calming effects than low potency antipsychotics such as chlorpromazine, which have dosages of several hundred milligrams.

There is generally a lag 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.

Some people who become psychotic do not seem to respond to antipsychotic medication, despite studies showing that the drug is blocking the same number of receptors as in other people who do respond to the treatment. In some cases this may be due to a misdiagnosed epileptic condition.

Side effects

The range of interactions can produce different adverse effects including extrapyramidal reactions, including acute dystonias, akathisia, rigidity and tremor, tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, seizures, and hyperprolactinaemia.

The atypical antipsychotics (especially olanzapine) seem to cause weight gain more commonly than the typical antipsychotics.

Clozapine also has a risk of inducing agranulocytosis, a potentially dangerous reduction in the number of white blood cells in the body. Because of this risk, patients prescribed clozapine may need to have regular blood checks to catch the condition early if it does occur, so the patient is in no danger.

One of the more serious of these side effects is tardive dyskinesia, in which the sufferer may show repetitive, involuntary, purposeless movements often of the lips, face, legs or torso. There is a greater risk of developing tardive dyskinesia with the older, typical antipsychotic drugs, although the newer antipsychotics do seem to cause this disorder to a lesser degree. It is believed that the possibility of tardive dyskinesia can be reduced by combining the anti-psychotics with diphenhydramine or benztropine.

Another serious side-effect is neuroleptic malignant syndrome, 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.

Whilst this may seem a daunting list, it must be noted that many people suffer few of the obvious side effects from taking antipsychotic medication. Some side-effects, such as subtle cognitive problems, foot rocking, or drooling, in the case of Akinesia go un-noticed.

Other symptoms of Akinesia of antipsychotics include deterioration of teeth due to a lack of saliva. These symptoms are hard to spot and are often dismissed.

History and design

The original antipsychotic drugs were happened upon largely by chance and were tested empirically for their effectiveness.

The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. It was first used on psychiatric 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.

The newer atypical antipsychotics are supposedly rationally designed drugs in which a theoretical understanding of both the condition to be treated and the effect of certain molecules on the body is used to develop potential new drug candidates.

See also

References

fr:Neuroleptique ja:抗精神病薬 nl:Antipsychoticum pt:Antipsicótico sv:Antipsykotika

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