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Chlorpromazine is authorised in the world under the following brand names: Chlorpromanyl (discontinued), Intensol, Largactil Liquid, Largactil Oral Drops, Novo-Chlorpromazine, Thorazine Spansule.

Typical Antipsychotics: Strategies to treat agitation, aggression and psychosis have evolved since the introduction of chlorpromazine in 1952. During the 1970s and early 1980s the approach of "more is better" led to high acute doses given to produce a rapid remission of psychotic symptoms (e.g., haloperidol 100 mg as a starting dose or giving an antipsychotic dose every 15 to 30 minutes until asleep). This approach was known as rapid neuroleptization. Fortunately, pharmacists now know that remission of psychosis is not sped up by high initial doses.

High doses possess a significant risk for extrapyramidal symptoms (EPS), especially acute dystonic reactions and neuroleptic malignant syndrome. The standard of care is to start with the long-term strategy in mind and give the lowest effective antipsychotic dose and allow time for a response. Acute agitation and aggression is best treated with short courses of antipsychotics or benzodiazepines after nondrug approaches have been tried. This approach is known as rapid tranquilization, which aims to control the agitated and potentially dangerous patient in a short period of time rather than trying to speed up the psychotic remission with high doses as in rapid neuroleptization.

All typical antipsychotics, when dosed equipotent, should produce the desired effects of decreasing agitation. Most antipsychotics are highly lipophilic and cross the blood-brain barrier. IM administration usually leads to clinical benefit within 30 minutes, while oral doses have an onset within 2 to 4 hours.

Haloperidol is the most widely studied typical antipsychotic in agitation, although studies also support other agents such as thiothixene, loxapine and chlorpromazine. The principal differences lie in the adverse effect risks; the agents differ by their affinity in binding to a-1, histaminergic, and cholinergic receptor sites, all of which are responsible for adverse effects. The lower potency agents are effective, but concerns surrounding orthostatic hypotension, rebound tachycardia, constipation, and excess sedation coupled with no evidence of superior efficacy make them a less desirable option for most patients.Haloperidol is currently the most commonly used antipsychotic in treating acute agitation because of its low affinity for these receptors. Droperidol, an antipsychotic more often used in anesthesia, can also be used to calm severely agitated patients as it has a more rapid onset of effect, a shorter duration of action, and lower incidence of EPS than haloperidol.One comparison study found IM or IV droperidol to be more effective than IM or IV haloperidol only in the initial 30 minutes of treatment. Droperidol, only available in parenteral form, may cause more hypotension than haloperidol, so it is usually reserved for patients who can have their blood pressure carefully monitored and need rapid control of dangerous behaviors.

Despite haloperidol’s cardiovascular safety, QTc prolongation and occasionally torsades de pointes have been reported, especially with IV use. Other antipsychotics, including droperidol, can also cause prolonged QTc, which appears to be dose dependent. The greatest risk of developing QTc prolongation with high-potency antipsychotics is in critically ill patients and when large doses are given intravenously. Droperidol was recently removed from the European market due to problems with QTc prolongation.

Haloperidol is more likely than the lower potency typical agents to cause dystonia (oculogyric [rotation of the eyeballs] crisis, retrocollis [the head twists to the back], and torticollis [the head twists to one side]), which generally occurs within the first week of antipsychotic exposure. The risk of dystonia is greatest in those males under 35 and with high-potency typical antipsychotics. Dystonia is preventable by giving an anticholinergic agent such as benztropine or diphenhydramine concurrently with the antipsychotic. If dystonia develops, IM benztropine or diphenhydramine should be given immediately. Dystonia is very distressing to patients and it can make them fearful or paranoid to take further doses of the medication.

Haloperidol and lorazepam are commonly administered in the same syringe as a single injection in order to lower the dose of haloperidol and improve response. (It is important to note that this mixture is stable only for 30 minutes.) Data suggest that combinations of IM haloperidol and lorazepam were more effective than single agents in reducing agitation in psychotic individuals initially, but differences disappeared after the first 2 to 4 hours.The primary reason for using combination therapy is more to reduce adverse effects than to improve efficacy.

Typical Antipsychotics vs. Benzodiazepines: Recently, an analysis of 24 studies that met a standard set of criteria regarding the treatment of acute agitation was published. These criteria included that the subjects were identified as being agitated, were given immediate treatment, and had appropriate follow-up monitoring. The trials included head-to-head comparisons of a wide range of low- and high-potency typical antipsychotics, benzodiazepine/antipsychotic combinations versus the agents given as single agents and antipsychotics versus benzodiazepines as single agents. The analysis found little difference in effectiveness that was not a result of kinetic or dosing differences, thereby giving clinicians the responsibility to make decisions based on parameters other than efficacy.