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It may be more useful to refer to antipsychotics as reality inducing drugs because the term has more positive connotations. This might make patients more well disposed to them and could also help to reduce to the social stigma attached to such drugs. Antipsychotics are also referred to as neuroleptic drugs, or simply '''neuroleptics'''. The word neuroleptic is derieved from Greek. 'Neuro' refers to the nerves and 'lept' means 'to take hold of'. Thus the word means 'taking hold of one's nerves' which implies their role in mood stabilization. There are currently two main types of antipsychotics in use, the Typical Antipsychotic s and Atypical Antipsychotic s. A new class of antipsychotic drugs has recently been discovered, known as Partial Dopamine Agonist s. 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. This term is increasingly disused because many newer antipsychotics do not have strong sedating properties and the terminology implies a connection with Benzodiazepine s, whereas none exists. COMMON ANTIPSYCHOTIC DRUGS Commonly used antipsychotic medications are listed below by drug group. Trade names appear in brackets.
Symbyax - (combination of olanzapine and fluoxetine used in the treatment of bipolar depression.)
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 are believed to 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. A recent multi-site, NIMH study published in 2005 comparing the atypicals to perphenazine found no greater efficacy for the atypicals, which had a side effect profile that was equal to or worse than the older drug. DRUG ACTION AND EFFECTIVENESS All antipsychotic drugs tend to block the D2 Receptors in the Dopamine pathways in the Brain , so the normal effect of dopamine release in the relevant Synapse s 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. A recent review , comparing the effectiveness of both typical and atypical antipsychotic medication, found little clinical advantage for atypical antipsychotics in reducing psychotic symptoms, although Olanzapine was associated with more weight gain and less chance of discontinuation. SIDE EFFECTS The range of interactions can produce different adverse effects including Extrapyramidal reactions, including acute Dystonia s, Akathisia , rigidity and Tremor , Tardive Dyskinesia , Tachycardia , Hypotension , Impotence , lethargy, Seizure s, and Hyperprolactinaemia . The atypical antipsychotics (especially Olanzapine ) seem to cause weight gain more commonly than the typical antipsychotics. The well documented metabolic side effects associated with weight gain include diabetes that, not infrequently, can be life threatening. 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. It is believed that there is a greater risk of developing tardive dyskinesia with the older, typical antipsychotic drugs, although the newer antipsychotics are now also known to cause this disorder. It is believed by some that the risk of tardive dyskinesia can be reduced by combining the anti-psychotics with Diphenhydramine or Benztropine , though this has not been established. Central Nervous System damage is also associated with irreversible Tardive Akathisia and Tardive Dementia . 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 unnoticed. 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 now some believe that it causes a reduction of psychosis unrelated to the sedating effect of the medication. It was introduced for the treatment of psychosis during the period when Lobotomy was a common treatment and was hailed as a "cure" for schizophrenia. It was then touted to provide a "chemical lobotomy," causing similar neurological effects without requiring surgery. 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
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