What are first-generation (1st gen) antipsychotics?

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Last updated: February 12, 2025View editorial policy

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From the Guidelines

First-generation antipsychotics are traditional neuroleptic medications, such as haloperidol and chlorpromazine, that primarily block dopamine receptors.

Characteristics of 1st Gen Antipsychotics

  • They are also known as typical antipsychotics
  • Examples include haloperidol and chlorpromazine 1
  • They are associated with a higher risk of extrapyramidal symptoms compared to atypical antipsychotics, especially in certain populations such as those with intellectual disability 1
  • They are still used in some cases, particularly when atypical antipsychotics are not available or are too expensive 1

Comparison to Atypical Antipsychotics

  • Atypical antipsychotics, such as risperidone and aripiprazole, are generally preferred over first-generation antipsychotics due to their more favorable side effect profile 1
  • Atypical antipsychotics have a variety of effects, including antagonism of serotonergic receptors, in addition to blocking dopamine receptors 1
  • Both types of antipsychotics can be effective for treating psychotic symptoms, but atypical antipsychotics may have some advantages in terms of efficacy and tolerability 1

From the Research

Definition of First-Generation Antipsychotics

  • First-generation antipsychotics, also known as typical antipsychotics, are a class of antipsychotic drugs that were introduced in the 1950s and were widely used until the introduction of second-generation antipsychotics in the 1990s 2.
  • Examples of first-generation antipsychotics include haloperidol, perphenazine, and chlorpromazine 3, 4.

Characteristics of First-Generation Antipsychotics

  • First-generation antipsychotics are dopamine blockers or dopamine partial agonists, which means they work by blocking or partially blocking the action of dopamine in the brain 2.
  • They are effective in reducing psychosis, regardless of the underlying diagnosis, and are not specific for treating schizophrenia 2.
  • First-generation antipsychotics have a range of side effects, including weight gain, akathisia, and movement disorders 3, 4.

Comparison with Second-Generation Antipsychotics

  • Second-generation antipsychotics are considered to have a stronger association with lipid abnormalities, such as dyslipidaemia, compared to first-generation antipsychotics 5.
  • However, the evidence for this association is inconsistent, and it is more valuable to consider the metabolic risks of specific antipsychotics rather than focusing on collective metabolic effects belonging to either antipsychotic group 5.

Clinical Use of First-Generation Antipsychotics

  • First-generation antipsychotics are still widely used in clinical practice, particularly in the emergency department for the treatment of acute agitation 6.
  • However, they are often not administered with adjunctive medications, such as benzodiazepines or anticholinergic medications, which can help to reduce side effects 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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