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).

[2] 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.

[5] For reference, the typical antipsychotic haloperidol tends to block about 80% of D2 receptors at doses ranging from 2 to 5 mg per day.

[5] Haloperidol, due to the availability of a rapid-acting injectable formulation and decades of use, remains the most commonly used antipsychotic for treating severe agitation in the emergency department setting.

[10] 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.

[11] 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.

Traditional antipsychotics are classified as high-potency, mid-potency, or low-potency based on their potency for the D2 receptor: Prochlorperazine (Compazine, Buccastem, Stemetil) and Pimozide (Orap) are less commonly used to treat psychotic states, and so are sometimes excluded from this classification.

[15] It is important to note that these methods do not generally account for differences between the tolerability (i.e. the risk of side effects) or the safety between medications.

The United Nations Special Rapporteur On Torture has classified this as a human rights violation and cruel or inhuman treatment.

[18] Together, these modifications prevent the active medications from being released immediately upon injection, attaining a slow release of the active medications (note, though, that the fluphenazine decanoate product is unique for reaching peak fluphenazine blood levels within 24 hours after administration[19]).

[31] (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.