Типик антипсихотиктер және олардың жанама әсерлері

Class of drugs

Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) 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 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 in the latter. Both generations of medication tend to block receptors in the brain's dopamine pathways, but atypicals at the time of marketing were claimed to differ from typical antipsychotics in that they are less likely to cause extrapyramidal symptoms (EPS), which include unsteady Parkinson's disease type movements, internal restlessness, and other involuntary movements (e. g. tardive dyskinesia, which can persist after stopping the medication). More recent research has demonstrated the side effect profile of these drugs is similar to older drugs, causing the leading medical journal The Lancet to write in its editorial "the time has come to abandon the terms first generation and second generation antipsychotics, as they do not merit this distinction." While typical antipsychotics are more likely to cause EPS, atypicals are more likely to cause adverse metabolic effects, such as weight gain and increase the risk for type II diabetes.

Typical antipsychotics block the dopamine 2 receptor (D2) receptor, causing a tranquilizing effect. It is thought that 60–80% of D2 receptors need to be occupied for antipsychotic effect. There is a risk of developing a serious condition called tardive dyskinesia as a side effect of antipsychotics, including typical antipsychotics. The risk of developing tardive dyskinesia after chronic typical antipsychotic usage varies on several factors, such as age and gender, as well as the specific antipsychotic used. 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 few treatments that have consistently been shown to be effective for the treatment of tardive dyskinesia, though an VMAT2 inhibitor like valbenazine may help. 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, withdrawal may also make tardive dyskinesia more severe. Neuroleptic malignant syndrome (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 typical antipsychotics may increase the risk of death in elderly patients. A 2005 retrospective cohort study from the New England Journal of Medicine 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.

Some typical antipsychotics have been formulated as a long acting injectable (LAI), or "depot", formulation. Depot injections are also used on persons under involuntary commitment to force compliance with a court treatment order when the person would refuse to take daily oral medication. This has the effect of dosing a person who doesn't consent to take the drug. The United Nations Special Rapporteur On Torture has classified this as a human rights violation and cruel or inhuman treatment. The first LAI antipsychotics (often referred to as simply "LAIs") were the typical antipsychotics fluphenazine and haloperidol. Both fluphenazile and haloperidol are formulated as decanoates, referring to the attachment of a decanoic acid group to the antipsychotic molecule.).]] The original antipsychotic drugs were happened upon largely by chance and then tested for their effectiveness. The first, chlorpromazine, was developed as a surgical anesthetic after an initial report in 1952. (Note that "tranquilizing" here only refers to changes in external behavior, while the experience a person has internally may be one of increased agitation but inability to express it.) Until the 1970s there was considerable debate within psychiatry on the most appropriate term to use to describe the new drugs. In the late 1950s the most widely used term was "neuroleptic", followed by "major tranquilizer" and then "ataraxic". The word neuroleptic was coined in 1955 by Delay and Deniker after their discovery (1952) of the antipsychotic effects of chlorpromazine. It is derived from the "[[wikt:νεῦρον (neuron, originally meaning "sinew" but today referring to the nerves) and "λαμβάνω" (lambanō, meaning "take hold of"). Thus, the word means taking hold of one's nerves. It was often taken to refer also to common effects such as reduced activity in general, as well as lethargy and impaired motor control. Although these effects are unpleasant and harmful, they were, along with akathisia, considered a reliable sign that the drug was working. These terms have been largely replaced by the term "antipsychotic" in medical and advertising literature, which refers to the medication's more marketable effects.