Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include muscle breakdown (rhabdomyolysis), high blood potassium, kidney failure, or seizures.
Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks for people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders with typical antipsychotics.
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.
Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as irritability associated with autism. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.
Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid, the benefits of such use may not outweigh the risk of undesirable side effects. It is taken orally.
Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.
Tardive dyskinesia (TD) is an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional motor symptoms include chorea or athetosis. In about 20% of people with TD, the disorder interferes with daily functioning. If TD is present in the setting of a long-term drug therapy, reversibility can be determined primarily by severity of symptoms and how long symptoms have been present before the long-term drug has been stopped.
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.
Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and is sometimes used in low dosage to treat anxiety and mild depression.
Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.
Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.
Melperone is an atypical antipsychotic of the butyrophenone chemical class, making it structurally related to the typical antipsychotic haloperidol. It first entered clinical use in 1960s.
Tardive psychosis is a hypothetical form of psychosis caused by long-term use of neuroleptics. It was first proposed in 1978 but was questioned by the late 1980s. It was hypothesized that psychosis could arise as neuroleptic medication become decreasingly effective, requiring higher doses, or when not responding to higher doses.
Pleurothotonus, commonly known as Pisa syndrome, is a rare neurological disorder which occurs due to prolonged exposure to antipsychotic drugs. It is characterized by dystonia, and abnormal and sustained involuntary muscle contraction. This may cause twisting or jerking movements of the body or a body part. Although Pisa syndrome develops most commonly in those undergoing long-term treatment with antipsychotics, it has been reported less frequently in patients receiving other medications, such as an acetylcholinesterase inhibitor. However, it has also been seen in those with other diseases causing neurodegeneration and in those who are not receiving any medication. The characteristic development of Pisa syndrome consists of two types of dystonia: acute dystonia and tardive dystonia. The underlying pathology of drug-induced Pisa syndrome is very complex, and development may be due to an underlying dopaminergic-cholinergic imbalance, or serotonergic/noradrenergic dysfunction.
Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.
Dopamine supersensitivity psychosis is a hypothesis that attempts to explain the phenomenon in which psychosis (e.g., hallucinations, delusions) occurs despite treatment with escalating doses of antipsychotics. Dopamine supersensitivity may be caused by the dopamine receptor D2 antagonizing effect of antipsychotics, causing a compensatory increase in D2 receptors within the brain that sensitizes neurons to endogenous release of the neurotransmitter dopamine. Because psychosis is thought to be mediated—at least in part—by the activity of dopamine at D2 receptors, the activity of dopamine in the presence of supersensitivity may paradoxically give rise to worsening psychotic symptoms despite antipsychotic treatment at a given dose. This phenomenon may co-occur with tardive dyskinesia, a rare movement disorder that may also be due to dopamine supersensitivity.
Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic. There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorized for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.
