Typical antipsychotic

Skeletal formula of chlorpromazine, the first neuroleptic drug

Typical antipsychotics (sometimes referred to as first generation antipsychotics, conventional antipsychotics, classical neuroleptics, traditional antipsychotics, or major tranquilizers) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). 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 phenothiazines. 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 disabilities in patients, which include unsteady Parkinson's disease-type movements, body rigidity and involuntary tremors. These abnormal body movements can become permanent even after medication is stopped.

Adverse effects

Further information: Phenothiazines

Side effects vary among the various agents in this class of medications, but common side effects include: dry mouth, muscle stiffness, muscle cramping, tremors, EPS and weight-gain. EPS is a cluster of symptoms consisting of akathisia, parkinsonism, dystonias. Anticholinergics such as benztropine and diphenhydramine are commonly prescribed to treat the symptoms of EPS. 4% of patients develop the Rabbit syndrome while on typical antipsychotics.

There is a significant risk of the serious condition tardive dyskinesia 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 acids, melatonin, and vitamin E have been suggested as possible treatments. The atypical antipsychotic clozapine 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, 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.

High-potency and low-potency

Traditional antipsychotics are classified as either high-potency or low-potency:

Potency	Examples	Adverse effect profile
high-potency	fluphenazine and haloperidol	more extrapyramidal side effects(EPS) and less histaminic (e.g. sedation), alpha adrenergic (e.g. orthostatic hypotension) and anticholinergic effects (e.g. dry mouth)
low-potency	chlorpromazine	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 decanoate) 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 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.

The oldest depots available were haloperidol and fluphenazine, with flupentixol and zuclopenthixol 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, and its metabolite, paliperidone, 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, clozapine, olanzapine, etc.

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 (Compazine, Buccastem, Stemetil) and Pimozide (Orap) are less commonly used to treat psychotic states, and so are sometimes excluded from this classification.

Low potency

• Chlorpromazine (Largactil, Thorazine)
• Chlorprothixene (Truxal)
• Thioridazine (Mellaril)
• Mesoridazine
• Levomepromazine

Medium potency

• Loxapine (Loxapac, Loxitane)
• Molindone (Moban)
• Perphenazine (Trilafon)
• Thiothixene (Navane)
• Trifluoperazine (Stelazine)

High potency

• Haloperidol (Haldol, Serenace)
• Fluphenazine (Prolixin)
• Droperidol
• Zuclopenthixol (Clopixol)
• Flupentixol (Depixol)
• Prochlorperazine

See also

• Atypical antipsychotic