Typical 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...
drugs first developed in the 1950s and used to treat psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
(in particular, 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...
). Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to enter clinical use were the phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
s. Second-generation antipsychotics are known as atypical antipsychotics.
Both generations of medication tend to block receptors in the brain's dopamine pathways, but compared to the typicals, the atypicals 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
Involuntary
Involuntary is the antonym of voluntary. An involuntary action is one that occurs without volition or will; see volition and will . Involuntary may also refer to:*Involuntary , a 2008 Swedish film by Ruben Östlund...
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.
High-potency and low-potency
Traditional antipsychotics are classified as either high-potency or low-potency:| Potency | Examples | Adverse effect profile >- | high-potency |
fluphenazine Fluphenazine Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines.... and haloperidol Haloperidol Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines.... |
extrapyramidal side effects Extrapyramidal system In human anatomy, the extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. The system is called "extrapyramidal" to distinguish it from the tracts of the motor cortex that reach their targets by traveling through... (EPS) and less histaminic (e.g. sedation Sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure... ), alpha adrenergic (e.g. orthostasis) and anticholinergic Anticholinergic An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine.... effects (e.g. dry mouth) >- | low-potency |
chlorpromazine Chlorpromazine Chlorpromazine is a typical antipsychotic... |
fewer EPS but more H1, α1, and muscarinic blocking effects |
Depot injections
Some of the high-potency antipsychotics have been formulated as the decanoate ester (e.g. fluphenazine decanoateFluphenazine
Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines....
) to allow for a slow release of the active drug when given as a deep, intramuscular injection. This has the advantage of providing reliable dosing for a person who doesn't want to take the medication. Depot injections can also be used for involuntary community treatment
Outpatient commitment
Outpatient commitment refers to mental health law that allows the compulsory, community-based treatment of individuals with mental illness.In the United States the term "assisted outpatient treatment" or "AOT" is often used and refers to a process whereby a judge orders a qualifying person with...
patients to ensure compliance with a community treatment order when the patient would refuse to take daily oral medication. Depot preparations were limited to high-potency antipsychotics so choice was limited. It is therefore preferable to use oral medications if the cooperation and compliance of the patient can be assured.
The oldest depots available were haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
and fluphenazine
Fluphenazine
Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines....
, with flupentixol
Flupentixol
Flupentixol , also known as flupenthixol , marketed under brand names such as Depixol and Fluanxol, is a typical antipsychotic drug of the thioxanthene class...
and zuclopenthixol
Zuclopenthixol
Zuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class...
as more recent additions. All have a similar, predominantly extrapyramidal, side effect profile though there are some variations between patients. More recently, long acting preparations of the atypical antipsychotic 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...
("Risperdal CONSTA"), and its metabolite, 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...
("INVEGA Sustenna") have become available, offering new choices. Risperidone still has a higher incidence of extrapyramidal effects than some other drugs available however, in particular, the benzodiazepine-derived atypical antipsychotics such as quetiapine
Quetiapine
Quetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
, 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...
, olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
, etc.
Common side effects
Side effects vary among the various agents in this class of medications, but common side effects include: dry mouth, muscleMuscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
stiffness, muscle cramping, 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, EPS
Extrapyramidal system
In human anatomy, the extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. The system is called "extrapyramidal" to distinguish it from the tracts of the motor cortex that reach their targets by traveling through...
and weight
Weight
In science and engineering, the weight of an object is the force on the object due to gravity. Its magnitude , often denoted by an italic letter W, is the product of the mass m of the object and the magnitude of the local gravitational acceleration g; thus:...
-gain. EPS is a cluster of symptoms consisting of 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...
, parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
, dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
s, anticholinergics such as benztropine
Benztropine
Benzatropine , also known as benztropine , is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, parkinsonism, akathisia, and dystonia.- Indications :...
and diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
are commonly prescribed to treat the symptoms of EPS. 4% of patients develop the Rabbit syndrome
Rabbit syndrome
Rabbit syndrome is a rare form of extrapyramidal side effect of antipsychotic drugs in which perioral tremors occur at a rate of 5 Hz. Rabbit syndrome is characterized by involuntary, fine, rhythmic motions of the mouth along a vertical plane, without involvement of the tongue...
while on typical antipsychotics.
Risks of serious side effects
There is a significant risk of the serious condition tardive dyskinesiaTardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
developing as a side effect of typical antipsychotics. The risk of developing tardive dyskinesia after chronic typical antipsychotic usage varies on several factors, such as age and gender. The commonly reported incidence of TD among younger patients is about 5% per year. Among older patients incidence rates as high as 20% per year have been reported. The average prevalence is approximately 30%. There are no treatments that have consistently been shown to be effective for the treatment of tardive dyskinesias, however branched chain amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, melatonin, and vitamin E have been suggested as possible treatments. The atypical antipsychotic 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...
has also been suggested as an alternative antipsychotic for patients experiencing tardive dyskinesia. Tardive dyskinesia may reverse upon discontinuation of the offending agent or it may be irreversible.
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...
, or NMS, is a rare, but potentially fatal side effect of antipsychotic treatment. NMS is characterized by fever, muscle rigidity, autonomic dysfunction, and altered mental status. Treatment includes discontinuation of the offending agent and supportive care.
The role of typical antipsychotics has come into question recently as studies have suggested that atypical antipsychotics may increase the risk of death in elderly patients. A retrospective cohort study from the New England Journal of Medicine on Dec. 1, 2005 showed an increase in risk of death with the use of typical antipsychotics that was on par with the increase shown with atypical antipsychotics. This has led some to question the common use of antipsychotics for the treatment of agitation in the elderly, particularly with the availability of alternatives such as mood stabilizing and antiepileptic drugs.
Typical medications
A measure of "chlorpromazine equivalence" is used to compare the relative effectiveness of antipsychotics. The measure specifies the amount (mass) in milligrams of a given drug that must be administered in order to achieve desired effects equivalent to those of 100 milligrams of chlorpromazine. Agents with a chlorpromazine equivalence ranging from 5 to 10 milligrams would be considered "medium potency", and agents with 2 milligrams would be considered "high potency".Prochlorperazine
Prochlorperazine
Prochlorperazine is a dopamine receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine...
(Compazine, Buccastem, Stemetil) and Pimozide
Pimozide
Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine . On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome...
(Orap) are less commonly used to treat psychotic states, and so are sometimes excluded from this classification.
Low potency
- ChlorpromazineChlorpromazineChlorpromazine is a typical antipsychotic...
(Largactil, Thorazine) - ThioridazineThioridazineThioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis...
(Mellaril) - MesoridazineMesoridazineMesoridazine is a piperidine neuroleptic drug belonging to the class of drugs called phenothiazines, used in the treatment of schizophrenia. It is a metabolite of thioridazine...
- LevomepromazineLevomepromazineLevomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug...
Medium potency
- LoxapineLoxapineLoxapine is a typical antipsychotic medication, used primarily in the treatment of schizophrenia. It is a member of the dibenzoxazepine class and as a dibenzazepine derivative, it is structurally related to clozapine...
(Loxapac, Loxitane) - MolindoneMolindoneMolindone is a therapeutic antipsychotic, used in the treatment of schizophrenia. It works by blocking the effects of dopamine in the brain, leading to diminished psychoses...
(Moban) - PerphenazinePerphenazinePerphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades....
(Trilafon) - ThiothixeneThiothixeneThiothixene is a typical antipsychotic drug of the thioxanthene class used in the treatment of psychoses like schizophrenia. It was introduced on July 24, 1967 by Pfizer.-Chemistry:*Bloom, B. M.; Muren, J. F.; 1967, See also:...
(Navane) - TrifluoperazineTrifluoperazineTrifluoperazine is a typical antipsychotic of the phenothiazine chemical class.- Uses :...
(Stelazine)
High potency
- HaloperidolHaloperidolHaloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
(Haldol, Serenace) - FluphenazineFluphenazineFluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines....
(Prolixin) - DroperidolDroperidolDroperidol is an antidopaminergic drug used as an antiemetic and antipsychotic...
- ZuclopenthixolZuclopenthixolZuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class...
(Clopixol) - ProchlorperazineProchlorperazineProchlorperazine is a dopamine receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine...