Antipsychotics: Uses, common brands, and safety info

What do industrial dyes have to do with drugs to help people with a mood disorder called schizophrenia? In the late 1800s, a commercial dye called methylene blue was discovered that was a derivative of phenothiazine. Methylene blue and phenothiazine intrigued medical researchers of the time, although tolerability issues halted most medical studies on both. In the 1930s, a French company made slight changes to the phenothiazine molecule to create promethazine, an antihistamine that was found to relieve psychotic symptoms of agitation and anxiety. This led to a path of discovery of antipsychotic drugs. 

The 1950s became known as the “Golden Age” of psychopharmacology (the study of the use of drugs to treat mental disorders) and the research during that time led to the availability of what is now known as “first-generation” or “typical” antipsychotic medicines. These drugs revolutionized the field of psychiatry and the treatment of schizophrenia, a mental illness that causes psychosis. The 1970s and beyond led to the introduction of “second generation” or “atypical” antipsychotic medicines. The table below lists available antipsychotic medicines followed by information on how they work, what conditions they treat, safety, and cost.

What are antipsychotics?

Antipsychotics are a type of psychiatric medication available by prescription to treat certain types of psychotic disorders—mental health problems whose symptoms include psychotic experiences. Antipsychotics are available in a variety of dosage forms, not just the common oral forms of tablets, capsules, and liquids. They are also given by injection including a depot injection—a long-acting form that is administered every few weeks. Other dosage forms include transdermal patches, powder for inhalation, and rectal suppositories. 

How do antipsychotics work?

Antipsychotics developed in the 1950s and 1960s are often referred to as first-generation or typical antipsychotics, while antipsychotics developed more recently are referred to as second-generation or atypical antipsychotics. Atypical antipsychotics aren’t necessarily more effective than typical, but they do have different side effects.

The exact mechanism of action of antipsychotic drugs is unknown, although it is thought both the first- and atypical medications reduce or eliminate symptoms of psychosis primarily by decreasing the activity of a brain chemical, or neurotransmitter, called dopamine. They may also have an effect on other neurotransmitters, including serotonin, noradrenaline, and glutamate, which are thought to regulate mood. Antipsychotic drugs don’t cure psychosis, but they can help to reduce and control many psychotic symptoms, such as delusions and hallucinations.

What are antipsychotics used for?

All antipsychotics play a vital role in treating symptoms of schizophrenia, however, they can also be used to treat the following conditions:

• Acute mania

• Bipolar disorder 

• Treatment-resistant depression

• Agitation

• Generalized (nonpsychotic) anxiety

• Hyperactivity

• Tourette syndrome

Types of antipsychotics

Although both typical and atypical antipsychotics treat schizophrenia, atypical antipsychotics are more commonly used to treat other conditions such as bipolar disorder, treatment-resistant depression, and acute mania. 

Typical antipsychotics

The typical or first-generation antipsychotics’ main action is thought to be the blocking of dopamine receptors in the brain resulting in decreased dopamine activity. Typical antipsychotics are more likely to be associated with drug-induced movement disorders, also known as extrapyramidal side effects. The symptoms may include spasms and muscle contractions, restlessness, rigidity, slowness of movement, tremors, and irregular, jerky movements. Examples of typical antipsychotics include:

• Haldol (haloperidol)

• Loxitane (loxapine)

• Mellaril (thioridazine)

• Moban (molindone)

• Navane (thiothixene)

• Prolixin (fluphenazine)

• Serentil (mesoridazine)

• Stelazine (trifluoperazine) 

Atypical antipsychotics 

Atypical, or second-generation, antipsychotics are less active on the dopamine receptors than typical. They are thought to have a greater effect on serotonin, which may be the reason they tend to have different side effects. Atypical antipsychotics are more likely to cause weight gain, which can lead to health complications such as diabetes or cardiovascular disease. Examples of atypical antipsychotics include:

• Abilify (aripiprazole)

• Clozaril (clozapine)

• Geodon (ziprasidone)

• Invega (paliperidone)

• Risperdal (risperidone)

• Seroquel (quetiapine)

• Vraylar (cariprazine)

• Zyprexa (olanzapine)

Who can take antipsychotics?

Antipsychotics are one of the most commonly prescribed classes of medications. In adults, both typical and atypical antipsychotic medications have shown to be effective for the treatment of schizophrenia, bipolar disorder, and treatment-resistant depression.

Patients will often experience relief of some symptoms, particularly agitation and hallucinations, within a few days of starting antipsychotic treatment although it may take several weeks for the full effects of the drug. Patients respond differently to the various antipsychotic therapies and it is not unusual to take several trials of different medications to find the most effective one.

Children and adolescents

Because atypical antipsychotics have a better safety record and similar efficacy compared to typical antipsychotics, they have been increasingly used in children and adolescents. Five medications have FDA approval for use in children and adolescents: 

1. Risperdal (risperidone)

2. Abilify (aripiprazole)

3. Zyprexa (olanzapine)

4. Invega (paliperidone)

5. Seroquel (quetiapine)

No antipsychotic is approved for use in children younger than 5 years old.

Although atypical antipsychotics are less likely to cause movement disorders (extrapyramidal side effects) than typical drugs, they are more likely to cause weight gain. Weight gain is even more probable in young patients taking more than one antipsychotic drug or when taking a second psychiatric drug. Antipsychotics may also cause sleepiness in younger patients.

Seniors

The number of older adults in our population is growing and many will experience psychiatric disorders, such as dementia. A majority of older adults with dementia will develop psychosis or agitation, and treatment of these symptoms often includes the use of antipsychotic medications. However, antipsychotics are associated with significant adverse effects, including increased risk of mental decline and increased risk of death.

The American Psychiatric Association (APA) provides recommendations on the use of antipsychotics to treat older patients with dementia. The guidelines have recommendations for assessing the patient’s status, development of a treatment plan, assessment of the risks and benefits of treating with antipsychotics, and guidance for dosing and monitoring.

Are antipsychotics safe?

Several antipsychotics have an FDA-mandated “boxed warning,” also called a black box warning, to alert consumers about serious or life-threatening side effects the drug may have.

• All antipsychotics have a boxed warning regarding their use in seniors with dementia-related psychosis having an increased risk of death primarily due to cardiovascular events or infections. 

• Atypical antipsychotics that are FDA approved for depression must also carry a boxed warning regarding the risk of increased suicidal thinking and behavior in some patients. 

• Zyprexa Relprevv (olanzapine injection) has a boxed warning regarding delirium and sedation following injection. 

• Clozaril (clozapine) has been associated with serious respiratory and cardiac events and has a boxed warning.

• Thioridazine and droperidol have boxed warnings regarding life-threatening arrhythmias.

Recalls

• Heritage Pharmaceuticals Inc. recall of prochlorperazine edisylate Injection, USP, 10mg/2mL (5mg/mL) due to sterility failure

Restrictions

Because individual antipsychotics have specific restrictions on who should not take the drug, patients should consult their healthcare professional before beginning any antipsychotic. In general, antipsychotics should be used with caution, or not at all, for those with the following conditions:

• Older patients with dementia-related psychosis

• A severe allergy 

• Simultaneous use of CNS depressants (e.g., barbiturates, benzodiazepines, opioids)

• Simultaneous use of an anticholinergic medication (e.g., scopolamine or phencyclidine)

• Severe cardiac abnormalities

• A history of seizure disorder

• Narrow-angle glaucoma 

• Prostatic hypertrophy

• History of or ongoing tardive dyskinesia (uncontrollable stiff, jerky movements of the face and body)

Can you take antipsychotics while pregnant or breastfeeding?

It is recommended that antipsychotics be avoided during pregnancy or, if necessary, should be used only if the benefits outweigh the risks. If possible, non-drug approaches to treatment should be considered. If an antipsychotic is necessary, the choice of drug should be determined by its safety data and by the individual patient’s medical history. 

Antipsychotics are secreted in breast milk therefore, it is advisable to avoid breastfeeding. A woman’s healthcare provider is the best source of information when managing antipsychotic treatment before becoming pregnant, during pregnancy, or while breastfeeding.

Are antipsychotics controlled substances?

No, antipsychotics are not controlled substances.

Common antipsychotics side effects

The following are potential common side effects of antipsychotics. Not all antipsychotics have these potential side effects (e.g., atypical antipsychotics are less likely to cause movement side effects). You should always consult a healthcare professional for advice regarding side effects before taking antipsychotics.

• Stiffness and shakiness

• Akathisia (restlessness)

• Tardive dyskinesia (uncontrollable stiff, jerky movements of the face and body)

• Sexual problems due to hormonal changes

• Drowsiness

• Weight gain

• Increased risk of Type 2 diabetes.

• Anticholinergic effects (dry mouth, constipation, urinary retention)

Extrapyramidal side effects

Extrapyramidal side effects, commonly referred to as drug-induced movement disorders are among the most common negative symptoms patients experience from the typical antipsychotic medications. There are four main symptoms: 

1. Pseudoparkinsonism: Symptoms resembling Parkinson’s disease such as tremor, mask-like facial expression, drooling, rigidity, and stiff gait. 

2. Akathisia: Feeling of restlessness that may lead to constant movement or inability to remain still for any length of time.

3. Acute dystonia: Spastic contractions of the muscles.

4. Tardive dyskinesia: Uncontrollable stiff, jerky movements of the face and body.

Weight gain

Weight gain is a common adverse effect of atypical antipsychotics and can be rapid and difficult to control. Younger patients are more likely to gain weight. Being overweight raises the risk of developing Type 2 diabetes and can increase the potential for heart attack, stroke, high blood pressure, arthritis, sleep apnea, and some cancers. Weight gain does not seem to be dose-dependent within the normal dosage range. The effect is worse with Clozaril (clozapine) and Zyprexa (olanzapine) and less likely with Abilify (aripiprazole) and Geodon (ziprasidone).

How much do antipsychotics cost?

Antipsychotics have a wide price range depending on the specific drug, quantity, and dosage. Typical, or first-generation, antipsychotics are available in generic form so overall, they are less expensive than the atypical, or second-generation, antipsychotics. Several of the atypical antipsychotics are also available as generics and they tend to be less than the brand-name counterpart. For example, generic olanzapine costs about $84 per 30, 5 mg tablets versus the brand-name version, Zyprexa, which could cost $413 for the same strength and quantity.

You can compare costs of generic vs. brand-name drugs on singlecare.com, and use a free SingleCare card to reduce certain prescription costs up to 80% at participating pharmacies.