First-Generation (Typical) Antipsychotics

This article provides a comprehensive overview of first-generation antipsychotics, with an emphasis on the specific types, indications, benefits, side effects, and treatment considerations.

Key Takeaways:

• First-generation (typical) antipsychotics were the first type of antipsychotic drugs developed. They work mainly by blocking dopamine activity in the brain, among other nervous system effects.
• Typical antipsychotics are used for schizophrenia, other instances of psychosis, agitation, and several other conditions and symptoms. Today, they are used less often due to the rise of atypical antipsychotics, which are less likely to cause extrapyramidal symptoms.
• Typical antipsychotics have many possible risks and drug interactions, some of which are severe and life-threatening. Talking with your doctor is essential to find a safe and effective treatment plan.

Understanding Typical Antipsychotics

First-generation antipsychotics, also called typical antipsychotics, refer to the first prescription antipsychotic drugs introduced to help manage symptoms of schizophrenia and other psychotic disorders. They were developed as early as the 1950s. ^[1]

Typical antipsychotics include several different groups, including phenothiazines, butyrophenones, thioxanthenes, dibenzoxazepines, dihydroindoles, and diphenylbutylpiperidines. Among these, the majority of typical antipsychotics fall within the phenothiazines group. ^[2]

How do Typical Antipsychotics Work?

Typical antipsychotics are all known to be strong dopamine receptor antagonists, which essentially inhibits the effects of dopamine in the brain. It is believed that these actions help control the primary symptoms of psychosis, such as delusions, agitation, and hallucinations. ^{[1] [3]}

First-generation antipsychotics may also inhibit histamine and cholinergic receptors to varying degrees. These effects also likely play a role, although not as significantly as dopamine blocking. ^{[1] [2]}

Typical vs Atypical Antipsychotics

Atypical antipsychotics are also known as second-generation antipsychotics. These medications work by blocking various forms of dopamine and serotonin receptors, whereas typical antipsychotics primarily work by blocking dopamine. ^[3]

One of the primary distinctions between typical and atypical antipsychotics is that typical antipsychotics are more likely to cause extrapyramidal symptoms compared to atypical antipsychotics. This is one of the main reasons why atypical antipsychotics are gradually replacing typical antipsychotics today. However, atypical antipsychotics generally have a higher risk of metabolic side effects, such as weight gain. Thus, there are pros and cons to both classes. ^{[2] [3] [4]}

In terms of overall effectiveness, atypical antipsychotics may have a bit broader application. For example, they can be used for both positive and negative symptoms of schizophrenia, while typical antipsychotics are most useful for positive symptoms only. ^{[3] [4]}

Types of Typical Antipsychotics

There are several types of typical antipsychotics. They are grouped below by specific category and include: ^{[1] [2] [3]}

• Phenothiazines:
• Prochlorperazine
• Triflupromazine
• Chlorpromazine
• Fluphenazine
• Perphenazine
• Thioridazine
• Butyrophenones:
• Haloperidol
• Thioxanthenes:
• Thiothixene
• Chlorprothixene
• Clopenthixol
• Flupenthixol
• Dibenzoxazepines:
• Loxapine
• Dihydroindoles:
• Molindone
• Dipheylbutylpiperidines:
• Pimozide

What Conditions Do They Treat?

First-generation antipsychotics are approved for several indications, including: ^[3]

• Schizophrenia and schizoaffective disorders:
• They can be used for acute instances of psychosis and as maintenance treatments. They are best to help control positive symptoms, which includes hallucinations, delusions, bizarre behaviors, and disorganized speech.
• Acute mania with psychotic symptoms:
• In these cases, they’re combined with mood stabilizers
• Major depressive disorder (MDD) with psychotic features:
• When combined with an antidepressant
• Delusional disorder
• Paranoia associated with personality disorders
• Tourette’s syndrome
• Borderline personality disorder
• Agitation within delirium or dementia
• Substance-induced psychotic disorder

Effects of Typical Antipsychotics

Typical antipsychotics have several common effects, all of which relate to their ability to inhibit dopamine neurotransmission and their other effects in the brain.

One of the effects of typical antipsychotics is a reduction of positive symptoms within schizophrenia. Positive symptoms are symptoms that are additions or abnormal changes to normal functioning. They include hallucinations, delusions, and disorganized thoughts and behaviors. ^{[1] [2]}

Typical antipsychotics can also help control agitation, anxiety, and irritability, especially if these are related to psychotic episodes. In addition, first-generation antipsychotics promote a more stabilized mood, clearer thinking, and improved functional abilities and behaviors.

Adverse Effects of Typical Antipsychotics

Typical antipsychotics are known to increase the likelihood of extrapyramidal symptoms, which refers to a group of movement-related side effects characterized by disruptions in the extrapyramidal system in the brain. Common extrapyramidal symptoms include: ^{[1] [2]}

• Tremor
• Slurred speech
• Dystonia (involuntary muscle contractions)
• Akathisia (inability to sit still; restlessness)
• Parkinsonism
• Characterized by tremors, muscle stiffness slow movements, and shuffled walk
• Tardive dyskinesia (uncontrollable movements, especially of the face, mouth, and tongue)

Other possible adverse effects of typical antipsychotics include: ^{[1] [5]}

• Sedation
• Blurred vision
• Dry mouth
• Constipation
• Tachycardia (rapid heart rate)
• Urinary retention
• Memory issues
• Hypotension (low blood pressure)
• Particularly postural/orthostatic hypotension
• Sexual dysfunction
• Erectile dysfunction in men
• Anorgasmia in women
• Breast enlargement
• Amenorrhea (absence of menstruation)

Some first-generation antipsychotics also have rare, but potentially serious side effects too, including neuroleptic malignant syndrome and heart rhythm abnormalities (such as QT prolongation). These can be fatal in severe instances. ^{[1] [3]}

Other rare, but potentially serious side effects of typical antipsychotics include leukopenia, blood dyscrasia, and thrombocytopenia. ^[3]

Who Shouldn’t Take Typical Antipsychotics?

Certain populations should only use typical antipsychotics very cautiously or potentially avoid them altogether. This includes: ^[3]

• Pregnant and nursing women
• Elderly adults
• Individuals with:
• Cardiovascular abnormalities
• A history of seizure disorder
• Narrow-angle glaucoma
• Prostatic hypertrophy
• Past or current tardive dyskinesia

Dangerous Drug Combinations

Typical antipsychotics have potentially serious and/or dangerous interactions with other drugs, including: ^{[3] [6]}

• Central nervous system depressants, such as:
• Benzodiazepines (e.g. alprazolam, clonazepam)
• Barbiturates (e.g. amobarbital, phenobarbital)
• Opioids (e.g. oxycodone, hydrocodone)
• Alcohol
• Anticholinergic medications (e.g. scopolamine, atropine)
• Certain antidepressants (e.g. fluoxetine, sertraline, paroxetine)
• Certain antifungals (e.g. ketoconazole)
• Certain antibiotics (e.g. clarithromycin)
• Protease inhibitors (e.g. ritonavir)

This is not an exhaustive list. Always consult your doctor and tell them everything you take, including prescription medications, herbs, supplements, and over-the-counter medicines.

How Long Does Antipsychotic Medication Treatment Last?

The length of antipsychotic medication treatment varies from person to person. In some cases, typical antipsychotics are only needed in the short-term for acute episodes of psychosis.

However, for schizophrenia and other disorders that involve recurrent or ongoing psychotic symptoms, antipsychotics are generally needed long-term to improve quality of life, allow for more normal daily functioning, and reduce the risk of returning symptoms. In these cases, antipsychotics are taken for several years, often lifelong.

Final Thought

Typical antipsychotics are not used as often today, due in part to the greater use of atypical psychotics. However, they still offer many potential benefits for schizophrenia, psychosis, and other conditions, and are sometimes the preferred treatment choice in certain instances. Ultimately, your doctor can help determine the best medication and overall treatment plan for your individual needs and circumstances.

Author

Jack Cincotta

Jack Cincotta holds a M.S. degree in Psychology. He is also a board-certified holistic health practitioner through AADP and an AFPA-certified holistic health coach and nutritionist.

Activity History - Last updated: March 19, 2026, Published date: March 19, 2026

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Reviewer

David MilesPharmD

David is a seasoned Pharmacist, natural medicines expert, medical reviewer, and pastor.

Activity History - Medically reviewed on April 8, 2026 and last checked on March 19, 2026