Typical Antipsychotics: Uses, common brands, and safety info

Typical antipsychotics, also known as first-generation antipsychotics, are an older class of drugs used in the treatment of schizophrenia as well as tics and outbursts associated with Tourette’s syndrome. This class of antipsychotic drugs was discovered by luck from the use of medication cocktails to prevent surgical shock. A French surgeon noted that the combination of a phenothiazine antihistamine and barbiturate made patients very calm and indifferent to their surroundings. From this, chlorpromazine, the earliest typical antipsychotic, was developed in 1950. Unfortunately, it would take a few years for the first patient to benefit from its effects due to the hesitation of the medical community to utilize the drug. Eventually, first-generation antipsychotics went on to replace what we would now consider near inhuman treatments such as electroconvulsive therapy and frontal lobe lobotomies.

First-generation antipsychotics available in the United States include chlorpromazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, thiothixene, trifluoperazine haloperidol, loxapine, and molindone. We will discuss their indications for use, how they work, and their safety. Please remember that drug choice for any individual may vary, and only your psychiatry or healthcare professional can decide if typical antipsychotic drugs are appropriate for you. 

What are typical antipsychotics?

Typical antipsychotics, sometimes also referred to as sedatives or tranquilizers, are an early class of drugs used to treat forms of psychosis, specifically those associated with schizophrenia and Tourette’s. They are also referred to as first-generation antipsychotics as they were developed early in the era of psychopharmacology. A class of second-generation antipsychotics, referred to as atypical antipsychotic medications, was developed years later. Some examples of the second generation class of antipsychotics are aripiprazole, olanzapine, paliperidone, quetiapine, Risperdal, and ziprasidone to name a few. Despite the fact that first-generation antipsychotics were a significant development in the pharmacologic treatment of psychosis, their use is not without the potential for serious side effects. The treatment of psychosis is a balance of controlling symptomology of the mental health disorder while also balancing quality of life and the effects of adverse events.

How do typical antipsychotics work?

Typical antipsychotics block the dopamine 2 (D2) receptor. Dopamine is a messenger between neuron cells in your brain. It is responsible for things such as motor control, focus, mood, emotions, stress response, and pleasure and reward-seeking. It is theorized that patients experiencing psychosis have an overactive dopamine signal, and the blockade of dopamine receptors, specifically D2, helps to control the uncontrolled, manic, psychotic symptoms of the event. 

The antipsychotic effect of typical antipsychotics is directly related to the drug’s potency for the D2 receptor. First-generation antipsychotics need to occupy anywhere from 60 to 80% of D2 receptors to have a therapeutic effect, and this can take several weeks of therapy to achieve. Unfortunately, as more dopaminergic blockade occurs, the prevalence of side effects also begins to increase. Specifically, extrapyramidal symptoms, or EPS, increase with dopamine blockade. The symptoms include uncontrolled muscle movements, neck spasms, rapid heartbeats, sweating, and tremors. 

What are typical antipsychotics used for?

• Schizophrenia

• Acute mania*

• Severe behavioral issues associated with oppositional defiant disorder

• Tics and vocal disturbances associated with Tourette’s syndrome*

• Irritability associated with autism*

• Delirium*

*Off-label use not approved by the Food and Drug Administration (FDA)

Types of typical antipsychotics 

Phenothiazines

Phenothiazines are a type of antihistamine that have antipsychotic and antiemetic properties. It is the larger of the two subclasses of typical antipsychotics. Phenothiazines have the ability to cause severe extrapyramidal symptoms and movement disorders as well as a potentially fatal neuroleptic malignant syndrome.

Examples of phenothiazines: Thorazine, Prolixin, Compazine, and Trilafon

Butyrophenones

Butyrophenones also work by a mechanism of action that blocks dopamine and they have antipsychotic and antiemetic effects. Haldol is a butyrophenone and is the most widely used typical antipsychotic. It also is also considered high-potency for dopamine blockade.

Example of butyrophenone: Haldol

Who can take typical antipsychotics?

Adults

Adult men and women can take typical antipsychotics. If a patient has ever had a hypersensitivity reaction to another first-generation antipsychotic, they should avoid any further use. Haldol decanoate must only be given intramuscularly. Haloperidol lactate can be given intravenously but is associated with an abnormal heart rhythm known as QT prolongation. Patients with pre-existing cardiac conditions should be monitored closely if typical antipsychotics are deemed necessary.

Seniors

Patients aged 55 and older are at a much greater risk of severe extrapyramidal side effects. Patients with Parkinson’s disease cannot use typical antipsychotics. This use is contraindicated. Typical antipsychotics increase the risk of death in older adults with dementia-related psychosis.

Children

Some typical antipsychotics are approved for limited use in children. Children may also be more susceptible to the cardiac effects of typical antipsychotics such as QT prolongation. As in every case, the benefit must outweigh the risk when choosing a first-generation antipsychotic.

Pregnant or breastfeeding women

There is a general lack of evidence to prove the safety of typical antipsychotics. They are generally regarded as last-line treatment for both psychosis and nausea and vomiting associated with pregnancy. If necessary, the cardiac function of the mother and child must be monitored. Typical antipsychotics can be passed into breast milk. A decision must be made between discontinuation of the drug or breastfeeding the child.

Are typical antipsychotics safe?

Typical antipsychotic recalls:

• Heritage Pharmaceuticals Inc.: Voluntary recall due to sterility test failure, May 2019

Typical antipsychotic restrictions

Do not take typical antipsychotics if you have a history of hypersensitivity to other first-generation antipsychotics.

Typical antipsychotics are not approved for use in older adults with dementia-related psychosis.

Typical antipsychotics are contraindicated in patients with Parkinson’s disease. It also should not be used if you have other conditions which slow your central nervous system such as extreme drowsiness, other sedative medications, and alcohol consumption.

Your doctor should be aware if you have ever had heart problems, chest pain, and a personal or family history of QT prolongation. Your doctor also should be aware of low blood pressure (hypotension), a history of seizures, thyroid dysfunction, and electrolyte imbalances. 

Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, uncoordinated movements that may develop in patients taking antipsychotics. Patients taking antipsychotics must be evaluated regularly for this condition.

Typical antipsychotics should be used cautiously in patients who are taking other central nervous system (CNS) active medications such as atypical antipsychotic drugs, benzodiazepines, antidepressants, and anticholinergic drugs.

Are typical antipsychotics controlled substances?

No, typical antipsychotics are not controlled substances.

Common typical antipsychotics side effects

Typical antipsychotics can cause a variety of adverse effects. Some are simply bothersome, while others can be life-threatening.

Common side effects include:

• Drowsiness, sedation

• Headache

• Dizziness

• Uncontrolled muscle movements

• Restlessness

• Anxiety

• Insomnia and sleep problems

• Irregular menstrual periods

• Akathisia

• Dry mouth

• Weight gain and metabolic changes

• Dystonia

• Constipation

Serious life-threatening side effects requiring immediate medical attention:

• Uncontrolled muscle movements of the face (chewing, smacking, tongue movement, eye movement)

• Muscle spasms of the neck or tightness in the throat

• Quick changes in mood and behavior

• Rapid heartbeat

• Shortness of breath

• Fever, chills cough, sore throat

• High fever

• Sweating

• Confusion

• Irregular heartbeats or chest flutters

• Tremors

How much do typical antipsychotics cost?

The typical antipsychotics are an older class of drugs, and they are available generically. Typically they are considered affordable even without prescription insurance. SingleCare provides discount coupons for up to 80% off the retail price. For instance, the most widely used typical antipsychotic, haloperidol, can cost about $35 on average without any type of medication coverage. With SingleCare, you can pay less than $11 for a one-month supply of the 5 mg pills. If your doctor is thinking of prescribing an antipsychotic for symptoms of schizophrenia or other psychosis-related conditions, check SingleCare for your best price.