Atypical antipsychotic
Encyclopedia
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
tranquilizing
Tranquilizer
A tranquilizer, or tranquilliser , is a drug that induces tranquility in an individual.The term "tranquilizer" is imprecise, and is usually qualified, or replaced with more precise terms:...
drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved for use in the treatment of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Some carry FDA approved indications
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
for acute mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
, bipolar
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
depression, psychotic agitation, bipolar maintenance, and other indications.
Both generations of medication tend to block receptors in the brain's dopamine pathways, but atypicals differ from typical antipsychotic
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
s in that they are less likely to cause extrapyramidal motor control
Motor control
Motor control are information processing related activities carried out by the central nervous system that organize the musculoskeletal system to create coordinated movements and skilled actions...
disabilities in patients, which include unsteady Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
-type movements, body rigidity and involuntary tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
s. These abnormal body movements can become permanent even after medication is stopped.
During the course of treatment atypical antipsychotics are associated with the following benefits; higher rate of responders, efficiency in patients with refractory disease, lower risk of suicides, better functional capacity and an improved quality of life. However, there has been considerable debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects, including tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, a serious movement disorder, neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
, and increased risk of stroke, sudden cardiac death, blood clots, and diabetes. Significant weight gain may also occur.
Medical uses
Atypically antipsycotics are typically used to treat schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
or bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
. They are also frequently used for agitation associated with dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
,anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
, and obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
. Some agents showing some benefits for these uses but are associated with significant rates of adverse events and are not approved by the United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for these purposes.
Schizophrenia
The first-line psychiatric treatment for schizophrenia is antipsychotic medication, which can reduce the positive symptoms of psychosis in about 7–14 days. Antipsychotics, however, fail to significantly ameliorate the negative symptoms and cognitive dysfunction.The choice of which antipsychotic to use is based on benefits, risks, and costs. It is debatable whether, as a class, typical oratypical antipsychotics are better. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. There is a good response in 40–50%, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two of three different antipsychotics) in 20% of people. Clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
is an effective treatment for those who respond poorly to other drugs, but it has the potentially serious side effect of agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
(lowered white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
count) in 1–4%.
Effectiveness
There has been considerable debate about whether second-generation antipsychotic drugs are better than first-generationantipsychotic drugs. It has been suggested that there is no validity to the term second-generation antipsychotic drugs and that the drugs that currently occupy this category are not identical to each other in mechanism, efficacy, and side-effect profiles:
...the second-generation drugs have no special atypical characteristics that separate them from the typical, or first-generation, antipsychotics. As a
group they are no more efficacious, do not improve specific symptoms, have no clearly different side-effect profiles than the first-generation antipsychotics, and are less cost effective. The spurious invention of the atypicals can now be regarded as invention only, cleverly manipulated by the drug industry for marketing purposes and only now being exposed.
Robert Whitaker suggests that the "wonder drug" glow around the second generation psychotropics has long since disappeared. He views the "hyping" of the top-selling atypicals as "one of the more embarrassing episodes in psychiatry's history, as one government study after another failed to find that they were any better than the first-generation anti-psychotics".
Adverse effects
The side effects reportedly associated with the various atypical antipsychotics vary and are medication-specific. Generally speaking, atypical antipsychotics are hoped to have a lower likelihood for the development of tardive dyskinesiaTardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
than the typical antipsychotics. However, tardive dyskinesia typically develops after long term (possibly decades) use of antipsychotics. It is not clear, then, if atypical antipsychotics, having been in use for a relatively short time, produce a lower incidence of tardive dyskinesia.
Akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
is more likely to be less intense with these drugs than the typical antipsychotics although many patients would dispute this claim. In 2004, the Committee for the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone should not be given to elderly patients with dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, because of an increased risk of stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
. Sometimes atypical antipsychotics can cause abnormal shifts in sleep patterns, and extreme tiredness and weakness.
In 2006, USA Today published an article about the effects of antipsychotic medication in children. None of the atypicals (Clozaril, Risperdal, Zyprexa, Seroquel, Abilify and Geodon) had been approved for children, and there was little research on their effects on children. From 2000–2004, there were 45 reported deaths in which an atypical antipsychotic was listed as the "primary suspect." There were also 1328 reports of serious, and sometimes life threatening, side effects. These include tardive dyskinesia (involuntary jerking and facial grimacing) and dystonia (involuntary muscle contractions that can interfere with talking and eating). Since the article's publication several of the atypicals now carry limited FDA approval for pediatric indications.
Some of the other side effects that have been suggested is that atypical antipsychotics increase the risk of cardiovascular disease. The research that Kabinoff et al., evaluated found that the increase in cardiovascular disease is seen regardless of the treatment they receive, instead it is caused by many different factors such as lifestyle or diet.
Sexual side effects have also been reported when taking atypical antipsychotics. In males antipsychotics reduce sexual interest, impair sexual performance with the main difficulties being failure to ejaculate. In females there may be abnormal menstrual cycles and infertility. In both males and females the breasts may become enlarged and a fluid will sometimes ooze from the nipples.
In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti psychotic use among elderly patients with dementia. The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia.
Tardive dyskinesia
All of the atypical antipsychotics warn about the possibility of tardive dyskinesiaTardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
in their package inserts and in the PDR
Physicians' Desk Reference
The Physicians' Desk Reference is a commercially published compilation of manufacturers' prescribing information on prescription drugs, updated annually...
. It is not possible to truly know the risks of tardive dyskinesia when taking atypicals, because tardive dyskinesia can take many decades to develop and the atypical antipsychotics are not old enough to have been tested over a long enough period of time to determine all of the long-term risks. One hypothesis as to why atypicals have a lower risk of tardive dyskinesia is because they are much less fat-soluble than the typical antipsychotics and because they are readily released from D2 receptor and brain tissue. The typical antipsychotics remain attached to the D2 receptors and accumulate in the brain tissue which may lead to TD.
Metabolism
Recently, metabolic concerns have been of grave concern to clinicians, patients and the FDA. In 2003, the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) required all manufacturers of atypical antipsychotics to change their labeling to include a warning about the risks of hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
and diabetes with atypical antipsychotics. It must also be pointed out that although all atypicals must carry the warning on their labeling, some evidence shows that atypicals are not equal in their effects on weight and insulin sensitivity. The general consensus is that clozapine and olanzapine are associated with the greatest effects on weight gain and decreased insulin sensitivity, followed by risperidone and quetiapine. Ziprasidone and aripiprazole are thought to have the smallest effects on weight and insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
, but clinical experience with these newer agents is not as developed as that with the older agents.
A study by Sernyak and colleagues found that the prevalence of diabetes in atypical antipsychotic treatments was statistically significantly higher than that of conventional treatment. The authors of this study suggest that it is a causal relationship the Kabinoff et al. suggest the findings only suggest a temporal association. Kabinoff et al. suggest that there is insufficient data from large studies to demonstrate a consistent or significant difference in the risk of insulin resistance during treatment with various atypical antipsychotics.
Pharmacokinetics
The most common route of administration of AAP is oral. Antipsychotics can also be injected, but this method is not as common. Once the antipsychotics are in the body they are lipid soluble and are readily absorbed from the digestive tract and can easily pass the blood brain barrier and placental barriers. Once in the brain the antipsychotics make their way to the synapse and work at the synapse by binding to the receptor (Culpepper, 2007). Antipsychotics are entirely destroyed by the body's metabolism and the metabolites are excreted in the urine (McKim, 2007). These drugs have relatively long half lives. Each drug has a different half life but the occupancy of the D2 receptor falls off within 24 hours with atypical antipsychotics, while lasting over 24 hours for the typical antipsychotics. This may explain why relapse into psychosis happens quicker with atypical antipsychotics than with typical antipsychotics, as the drug is excreted faster and is no longer working in the brain. Physical dependence with these drugs is very rare, therefore withdrawal symptoms are rarely seen. Sometimes if AAP are abruptly stopped psychotic symptoms, movement disorders and difficulty in sleep are seen. It is possible that withdrawal is rarely seen is because the AAP are stored in the fat tissues in the body and slowly released).Pharmacology
The mechanism of action of these agents is unknown, and differs greatly from drug to drug.The variation in the receptor binding profile is such that the only effect all have in common is an anti-psychotic effect; the side effect profiles vary tremendously. The mechanisms behind atypical antipsychotic action are not clear. All antipsychotics work on the dopamine system but all vary in regards to the affinity to the dopamine receptors. There are 5 types of dopamine receptors in humans. There are the “D1-like” group which are types 1 and 5 which are similar in structure and drug sensitivity. The “D2-like” group includes dopamine receptors 2, 3 and 4 and have a very similar structure but very different sensitivities to antipsychotic drugs.
The “D1-like” receptors have been found to not be clinically relevant in therapeutic action. If D1 receptors were a critical component of the mechanism of AAP blocking just the D1 receptor would improve the psychiatric symptoms that are exhibited. If D1 receptor binding was a critical component of the action of antipsychotics they would need to be present in maintenance dosages. This is not seen. They are not present or present in low or negligible levels which would not even maintain the elimination of the symptoms that are seen.
The “D2-like” group of dopamine receptors are classified together based on structure but not drug sensitivity. It has been shown that D2 receptor blockade is necessary for action. All antipsychotics block D2 receptors to some degree, but the affinity of the antipsychotics vary from drug to drug and it has been hypothesized that it is the varying in affinities that causes a change in effectiveness (Horacek et al., 2002).
One theory for how atypicals work is the “fast-off” theory. This theory of antipsychotic action is that AAP have low affinities for the D2 receptor and only bind loosely to the receptor and are rapidly released. In fact, the AAP bind more loosely to the D2 receptor than dopamine itself. The AAP effectively interfere with the phasic release of endogenous dopamine. The AAP transiently bind and rapidly dissociate from the D2 receptor to allow normal dopamine transmission. It is this transient binding that that keeps prolactin levels normal, spares cognition and obviates EPS.
From a historical point of view there has been interest in the role of serotonin and treatment with the use antipsychotics. Experience with LSD suggests that 5-HT2A receptor blockade may be a promising method of treating schizophrenia. One problem with this is the fact that psychotic symptoms caused by 5-HT2 receptor agonists differs substantially from the symptoms of schizophrenic psychoses. One promising factor of this is where the 5-HT2A receptors are located in the brain. They are localized on hippocampal and cortical pyramidal cells and have a high density in the fifth neocortex layer where the inputs of various cortical and subcortical brain areas are integrated. This makes the blocking of this receptor an interesting area considering these areas in the brain are of interest in the development of schizophrenia. This is an area of research that could prove convincing but has not yielded any convincing results. Evidence points to the fact that serotonin is not sufficient to produce an antipsychotic effect but serotonergic activity in combination with D2 receptor blockade may be responsible. Regardless of the neurotransmitters these AAP have an effect on antipsychotic drugs appear to work by inducing restructuring of neuronal networks. They are able to induce these structural changes.
List of atypical antipsychotics
The following are approved and marketed in various parts of the world:- AmisulprideAmisulprideAmisulpride , is an atypical antipsychotic used to treat psychosis in schizophrenia and episodes of mania in bipolar disorder. In small doses it is also used to treat depression. It was introduced by Sanofi-Aventis in the 1990s.-Pharmacology:Amisulpride functions primarily as a D2 and D3 receptor...
(Solian) - AripiprazoleAripiprazoleAripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
(Abilify) - AsenapineAsenapineAsenapine is a new atypical antipsychotic developed for the treatment of schizophrenia and acute mania associated with bipolar disorder by Schering-Plough after its November 19, 2007 merger with Organon International. Development of the drug, through Phase III trials, began while Organon was still...
(Saphris) - BlonanserinBlonanserinBlonanserin is a relatively new atypical antipsychotic commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia...
(Lonasen) - ClotiapineClotiapineClotiapine is an atypical antipsychotic of the dibenzothiazepine chemical class.It is structurally analogous to quetiapine.-External links:...
(Entumine) - ClozapineClozapineClozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
(Clozaril) - IloperidoneIloperidoneIloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia. It was approved by the U.S...
(Fanapt) - LurasidoneLurasidoneLurasidone is an atypical antipsychotic developed by Dainippon Sumitomo Pharma. It was approved by the U.S. Food and Drug Administration for treatment of schizophrenia on October 28, 2010 and is currently pending approval for the treatment of bipolar disorder in the United States.-...
(Latuda) - MosapramineMosapramineMosapramine is an atypical antipsychotic used in Japan. It is a potent dopamine antagonist with high affinity to the D2, D3, and D4 receptors, and with moderate affinity for the 5-HT2 receptors.- References :...
(Cremin) - OlanzapineOlanzapineOlanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
(Zyprexa)
- PaliperidonePaliperidonePaliperidone , also known as 9-hydroxyrisperidone, is an atypical antipsychotic developed by Janssen Pharmaceutica. Invega is an extended release formulation of paliperidone that uses the OROS extended release system to allow for once-daily dosing...
(Invega) - PerospironePerospironePerospirone is an atypical antipsychotic of the azapirone chemical class. It was introduced in Japan in 2001 by Dainippon Sumitomo Pharma for the treatment of schizophrenia and acute bipolar mania. Perospirone acts as a 5-HT1A receptor partial agonist, 5-HT2A receptor inverse agonist, and D2, D4,...
(Lullan) - QuetiapineQuetiapineQuetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
(Seroquel) - RemoxiprideRemoxiprideRemoxipride is an atypical antipsychotic which was previously used in Europe for the treatment of schizophrenia but was withdrawn due to toxicity concerns . It was initially launched by AstraZeneca in 1990 and suspension of its use began in 1993...
(Roxiam) - RisperidoneRisperidoneRisperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
(Risperdal) - SertindoleSertindoleSertindole is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company H. Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of...
(Serdolect) - SulpirideSulpirideSulpiride is an...
(Sulpirid, Eglonyl) - ZiprasidoneZiprasidoneZiprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
(Geodon, Zeldox) - ZotepineZotepineZotepine is an atypical antipsychotic indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 and Japan since 1982.- Pharmacology :...
(Nipolept)
And these are currently under development but are not yet licensed:
- BifeprunoxBifeprunoxBifeprunox is a novel atypical antipsychotic agent which, along with SLV313, aripiprazole, and SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism....
(DU-127,090) - PimavanserinPimavanserinPimavanserin is a drug developed by Acadia Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A, with 10x selectivity over 5-HT2C, and no significant affinity or activity at 5-HT2B or dopamine receptors...
(ACP-103) - VabicaserinVabicaserinVabicaserin was a novel antipsychotic and anorectic under development by Wyeth. As of 2010 it is no longer in clinical trials for the treatment of psychosis...
(SCA-136)
History
The first atypical anti-psychotic medication, clozapineClozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, was discovered in the 1950s
1950s
The 1950s or The Fifties was the decade that began on January 1, 1950 and ended on December 31, 1959. The decade was the sixth decade of the 20th century...
, and introduced into clinical practice in the 1970s
1970s
File:1970s decade montage.png|From left, clockwise: US President Richard Nixon doing the V for Victory sign after his resignation from office after the Watergate scandal in 1974; Refugees aboard a US naval boat after the Fall of Saigon, leading to the end of the Vietnam War in 1975; The 1973 oil...
. Clozapine fell out of favor due to concerns over drug-induced agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
. With research indicating its effectiveness in treatment-resistant schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and the development of an adverse event monitoring system, clozapine reemerged as a viable antipsychotic. According to Barker (2003) the three most accepted atypical drugs are; clozapine, risperidone and olanzapine. However, he goes on to explain that clozapine is usually the last resort when other drugs fail. Clozapine can cause agranulocytosis (which is decreased number of white blood cells), Barker (2003) explains that a person on clozapine will have to go through rigorous blood monitoring. Despite the effectiveness of clozapine for treatment-resistant schizophrenia, agents with a more favourable side effect profile were sought after for widespread use. During the 1990s
1990s
File:1990s decade montage.png|From left, clockwise: The Hubble Space Telescope floats in space after it was taken up in 1990; American F-16s and F-15s fly over burning oil fields and the USA Lexie in Operation Desert Storm, also known as the 1991 Gulf War; The signing of the Oslo Accords on...
, olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
, risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
and quetiapine
Quetiapine
Quetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
were introduced, with ziprasidone
Ziprasidone
Ziprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
and aripiprazole
Aripiprazole
Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
following in the early 2000s. The atypical anti-psychotic paliperidone
Paliperidone
Paliperidone , also known as 9-hydroxyrisperidone, is an atypical antipsychotic developed by Janssen Pharmaceutica. Invega is an extended release formulation of paliperidone that uses the OROS extended release system to allow for once-daily dosing...
was approved by the FDA in late 2006.
The atypical anti-psychotics have found favour among clinicians and are now considered to be first line treatments for schizophrenia and are gradually replacing the typical
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
s. In the past, most researchers have agreed that the defining characteristic of an atypical antipsychotic is the decreased propensity of these agents to cause extrapyramidal
Extrapyramidal
Extrapyramidal can refer to:* Extrapyramidal system* Extrapyramidal symptoms...
side effects (EPS) and an absence of sustained prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
elevation.
The terminology can be imprecise. The definition of "atypicality" was based upon the absence of extrapyramidal side effects, but there is now a clear understanding that atypical antipsychotics can still induce these effects (though to a lesser degree than typical antipsychotics.) Recent literature focuses more upon specific pharmacological actions, and less upon categorization of an agent as "typical" or "atypical". There is no clear dividing line between the typical and atypical antipsychotics therefore categorization based on the action is difficult.
More recent research is questioning the notion that second generation anti-psychotics are superior to first generation typical anti-psychotics. Using a number of parameters to assess quality of life, Manchester University
University of Manchester
The University of Manchester is a public research university located in Manchester, United Kingdom. It is a "red brick" university and a member of the Russell Group of research-intensive British universities and the N8 Group...
researchers found that typical anti-psychotics were no worse than atypical anti-psychotics. The research was funded by theNational Health Service
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
(NHS) of the UK. Because each medication (whether first or second generation) has its own profile of desirable and adverse effects, a neuropsychopharmacologist may recommend one of the older ("typical" or first generation) or newer ("atypical" or second generation) antipsychotics alone or in combination with other medications, based on the symptom profile, response pattern, and adverse effects history of the individual patient.