Reference Guide to Antipsychotic Medications

Highlights 

• Psychosis refers to the inability to distinguish between what’s real and what isn’t. 
• Common psychosis conditions include bipolar disorder, schizophrenia, and some types of depression.
• Antipsychotic medications come in two categories: typical and atypical.
• Typical antipsychotic medications have been shown to increase the risk of movement-related side effects, while atypical antipsychotic medications may lower this risk.
• Antipsychotics have been shown to increase the mortality rate in elderly individuals with dementia-related psychosis.

Psychosis is characterized by perceptions and thoughts that blur the line between what is real and what isn’t. Research estimates that psychosis will affect 3 in 100 individuals at some point in their lifetimes. For many, antipsychotic medications allow them to regain a sense of control and normalcy. 

Common forms of psychosis include:

• Schizophrenia
• Bipolar disorder
• Certain types of depression
• Delusional disorder

For example, a person might think that someone on TV is directly talking to them or sending them messages. Or they might hallucinate and see, hear, or taste things that aren’t real.

No matter the specific condition, antipsychotic medications may provide relief from symptoms so patients can live a higher quality of life. Learn more about how antipsychotics work, the different types of antipsychotic medications, and how to find the lowest price for prescriptions in this guide.

How Do Antipsychotic Medications Work?

Antipsychotic medications, also called neuroleptics, are a class of drugs used to treat various mental health conditions. They work by affecting the balance of neurotransmitters in the brain — primarily dopamine and serotonin. These are neurotransmitters that regulate mood, emotions, and perception.

In psychotic conditions like schizophrenia, there is usually an excess of dopamine activity in certain brain regions. Antipsychotic medications help reduce this excess. Specifically, typical antipsychotics bind to D2 receptors in the brain to reduce dopamine’s effects, which reduces hallucinations and delusions.

In atypical antipsychotics, the medication will interact with other neurotransmitters, such as serotonin. This additional mechanism can improve mood and cognitive function and reduce some of the side effects associated with typical antipsychotics. 

The precise mechanism of action can vary from drug to drug. Individual responses can also vary, which is why their use is closely monitored by healthcare providers. 

Antipsychotics can be broadly classified into two subtypes: typical (first-generation) and atypical (second-generation). These categories refer to when the drugs were developed and their mechanism of action. 

Here’s more information on both subtypes.

Typical Antipsychotics

Typical antipsychotics are the “traditional” medications developed to treat psychosis. These medications work to reduce dopamine activities in the brain. 

The following is a list of all typical antipsychotic medications currently approved by the FDA and their uses: 

• Haloperidol (Haldol). Used for the treatment of schizophrenia, acute psychosis, and Tourette’s syndrome.
• Fluphenazine (Prolixin and others). Used for the treatment of schizophrenia and rebalances dopamine to improve thinking, mood, and behavior.
• Chlorpromazine (Thorazine and Largactil). Used for psychotic disorders, preoperative apprehension, and other conditions.
• Perphenazine (Trilafon and others). Used for the treatment of schizophrenia and for the control of severe nausea and vomiting in adults.
• Trifluoperazine (Stelazine). Used for the treatment of schizophrenia and for short-term treatment of generalized non-psychotic anxiety. 
• Loxapine (Loxitane and Adasuve powder). Used for the treatment of schizophrenia and is also indicated for the management of the manifestations of psychotic disorders.
• Pimozide (Orap). Used for Tourette’s syndrome.
• Thiothixene (Navane). Used for schizophrenia.

Warnings and Contraindications

While typical antipsychotics have been shown to be effective in reducing positive symptoms of psychosis, such as hallucinations and delusions, they also carry a risk of significant side effects.

Warnings and contraindications vary by medication. Following is a list of warnings related to typical antipsychotics as a group. 

Warnings

• Increased mortality in elderly patients with dementia-related psychosis. These medications are not approved for the treatment of dementia-related psychosis and are associated with an increased risk of death in elderly patients.
• Severe central nervous system (CNS) depression. Typical antipsychotics can cause sedation and can increase the effects of other central nervous system depressants.
• Severe cardiovascular disorders. These drugs should be used with caution in patients with heart disease due to the risk of hypotension and arrhythmias.
• History of seizures. As these medications can lower the seizure threshold, they should be used with caution in patients with a seizure disorder.
• Liver disease. Caution is advised when prescribing these drugs to patients with liver disease as they are metabolized by the liver.
• Renal disease. Adjustments in dosage may be necessary in patients with kidney disease.
• Prostatic hypertrophy. These medications can exacerbate urinary retention and should be used with caution in patients with prostatic hypertrophy.
• Glaucoma. Antipsychotics can increase intraocular pressure and should be used with caution in patients with glaucoma.

Contraindications (Who Should Not Take These Drugs)

• Known hypersensitivity to the drug. Patients with a known allergy to a specific typical antipsychotic should not take that medication.
• Comatose or severely depressed states. These drugs should not be used in patients who are comatose or have severe central nervous system depression.
• Bone marrow suppression. Patients with a history of bone marrow suppression should not be treated with typical antipsychotics.
• Liver failure. These drugs are contraindicated in patients with severe liver failure.
• Blood dyscrasias. Patients with certain blood disorders should not take typical antipsychotics.
• Interactions with other drugs. These drugs can react with other medications, so always check with a doctor or pharmacist before starting anything new. See more about drug interactions below. 

Please note that this information is a general guide and may not include all warnings and contraindications for every typical antipsychotic. And not all warnings apply to all drugs in this subtype. 

For warnings and contraindications for a specific medication, talk to your doctor or search the FDA database for the labeling information for that drug. 

Side Effects

Like warnings and precautions, potential side effects will vary from one typical antipsychotic to another. Following is a list of side effects that are commonly seen with medications in this subtype. 

• Extrapyramidal symptoms (EPS). These include acute dystonia (muscle spasms, stiffness), akathisia (restlessness), parkinsonism (symptoms similar to Parkinson’s disease), and bradykinesia (slowness of movement).
• Tardive dyskinesia (TD). This is a serious and often irreversible condition that causes repetitive, involuntary movements, most often affecting the mouth, lips, and tongue.
• Neuroleptic malignant syndrome (NMS). A rare but life-threatening reaction that can cause a high fever, stiff muscles, confusion, irregular pulse or blood pressure, a fast heart rate (tachycardia), sweating, and rapid breathing.
• Sedation. Many typical antipsychotics can cause sedation or drowsiness, which may impair alertness and affect the ability to drive or operate machinery.
• Anticholinergic effects. These include dry mouth, blurred vision, constipation, urinary retention, and cognitive impairment.
• Orthostatic hypotension. A drop in blood pressure upon standing that can cause dizziness or fainting.
• Photosensitivity. Increased sensitivity to sunlight, leading to sunburns or skin rashes, can occur with the use of typical antipsychotics.
• Weight gain. Some typical antipsychotics can lead to an increase in weight, which may be associated with other metabolic changes.
• Sexual dysfunction. This can include decreased libido, erectile dysfunction, and other disruptions to sexual health.
• Agranulocytosis. Particularly with certain typical antipsychotics like thioridazine, there can be a risk of a significant drop in white blood cell count.
• Increased prolactin levels (hyperprolactinemia).These medications can cause menstrual irregularities, galactorrhea (inappropriate lactation), and changes in libido. Hyperprolactinemia can also cause other symptoms, such as headaches, fatigue, and decreased bone density.
• Cardiac issues. Some of these drugs can affect the heart’s rhythm, potentially leading to arrhythmias. However, this is a more common side effect of atypical antipsychotics than typical antipsychotics.
• Blood disorders. There is a risk of agranulocytosis (a potentially fatal drop in white blood cells) with some typical antipsychotics. However, this effect is most likely with clozapine, an atypical antipsychotic.
• Liver function abnormalities. Some of these medications can cause changes in liver enzymes and, in rare cases, lead to liver damage.

Again, the side effect profile can vary significantly from one medication to another within this subtype. Additionally, the severity and occurrence of side effects can depend on your age, dosage, duration of treatment, and other medical conditions. 

If you’re taking any of these medications, you should be closely monitored by your healthcare provider for side effects, especially when starting a new medication or changing doses.

Drug Interactions

Typical antipsychotics can interact with a variety of other medications, which can affect how well the medications work or increase the risk of side effects. 

Here’s a brief summary of potential drug interactions with typical antipsychotics:

• Central nervous system (CNS) depressants. Combining antipsychotics with other drugs that slow down the brain’s processes, like sleeping pills, anxiety medication, or strong painkillers, can lead to increased drowsiness, difficulty breathing, and other serious side effects.
• Anticholinergics. These drugs are used for various conditions, including gastrointestinal disorders. They include atropine, Ditropan, and allergy medications like Benadryl. When taken with typical antipsychotics, they can increase the risk of side effects like dry mouth, constipation, and trouble urinating. Anticholinergics can also cause other side effects, such as blurred vision, drowsiness, and cognitive impairment.
• Blood pressure medications. Antipsychotics can lower blood pressure, so taking them with blood pressure medications, like beta blockers or ACE inhibitors, can cause blood pressure to drop too low, leading to dizziness or fainting.
• Anticonvulsants. These are medications used to control seizures, including antiseizure medications like valproic acid (Depakote) and mood stabilizers, such as lamotrigine (Lamictal) and topiramate (Topamax). Some anticonvulsants can affect the levels of antipsychotics in the blood, which can decrease their effectiveness or increase side effects.
• Antidepressants. Some antidepressants can interact with antipsychotics, potentially leading to an increased risk of side effects or affecting how well either medication works. These include medications like amitriptyline (Elavil), fluoxetine (Prozac), sertraline (Zoloft), and others. 
• Anticoagulants. These medications help prevent blood clots and include warfarin (Coumadin) and apixaban (Eliquis). Antipsychotics can increase the risk of bleeding if taken with anticoagulants. However, this is more likely to happen with atypical antipsychotics than typical antipsychotics.
• Antiarrhythmics. These are drugs used to treat irregular heartbeats. Examples are amiodarone (Cordarone) and sotalol (Betapace) They can interact with antipsychotics and may increase the risk of heart rhythm problems. This is also more common with atypical antipsychotics than typical antipsychotics.
• Substances that affect liver enzymes. Many typical antipsychotics are broken down in the liver. Taking them together with drugs that affect liver enzymes — such as rifadin (Rifampin, used to treat tuberculosis) or phenytoin (Dilantin, an anticonvulsant) — can lead to increased levels of the antipsychotic in the body, which can increase side effects. Ketoconazole (an antifungal medication) and grapefruit juice can also have this effect. 

Lists of potential drug interactions are never complete, and interactions vary among the different medications in this subtype. It’s a good idea to check the Drugs.com Drug Interaction Checker for a list of interactions for the specific medication you’re taking.

Note also that it’s important that you inform your healthcare providers about all the medications you take, including over-the-counter drugs, supplements, and herbal products, to avoid harmful interactions. Your providers can then monitor for interactions and make adjustments to your treatment plan as necessary.

Atypical Antipsychotics

Atypical antipsychotics are “second-generation” antipsychotic medications because they’re newer formulas that have a broader mechanism of action. They have been shown to be effective in improving positive and negative symptoms of psychosis and carry a lower risk of movement-related side effects.

Currently, about 95% of antipsychotic medication prescriptions are atypical antipsychotics.

Common examples of atypical antipsychotic medications include:

• Aripiprazole (Abilify). Used for the treatment of schizophrenia, bipolar disorder, depression, and as an adjunct for major depressive disorder.
• Asenapine (Saphris). Indicated for schizophrenia and the manic or mixed episodes associated with bipolar I disorder.
• Brexpiprazole (Rexulti). Approved for the treatment of schizophrenia and as an add-on treatment for major depressive disorder.
• Cariprazine (Vraylar). Used for the treatment of schizophrenia and bipolar disorder.
• Clozapine (Clozaril). Indicated for treatment-resistant schizophrenia and to reduce the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.
• Iloperidone (Fanapt). Approved for the treatment of schizophrenia.
• Lurasidone (Latuda). Used for the treatment of schizophrenia and depressive episodes associated with bipolar I disorder.
• Olanzapine (Zyprexa). Indicated for the treatment of schizophrenia and bipolar disorder.
• Paliperidone (Invega). Approved for the treatment of schizophrenia and schizoaffective disorder.
• Quetiapine (Seroquel). Used for the treatment of schizophrenia, bipolar disorder, and as an adjunct for major depressive disorder.
• Risperidone (Risperdal). Indicated for the treatment of schizophrenia, bipolar I disorder, and irritability associated with autistic disorder.
• Ziprasidone (Geodon). Approved for the treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar disorder.

Warnings and Contraindications

Following are general guidelines for atypical antipsychotics, but they vary from drug to drug in this subtype. Review the specific warnings, precautions, and contraindications of your specific medication with your provider or the FDA Database label information.

Warnings

• Increased mortality in elderly patients with dementia-related psychosis. These patients have a higher risk of death when treated with antipsychotic drugs.
• Cerebrovascular adverse events, including stroke. These medications can increase risk of stroke in elderly patients. 
• Neuroleptic malignant syndrome (NMS). This is a rare but life-threatening condition that can cause high fever, muscle stiffness, confusion, irregular pulse or blood pressure, a fast heart rate (tachycardia), sweating, and rapid breathing.
• Tardive dyskinesia. This is a syndrome of potentially irreversible, involuntary muscle movements.
• Metabolic changes. Atypical antipsychotics can increase cardiovascular or cerebrovascular risk, including hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain.
• Pathological gambling and other compulsive behaviors. Compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex have been reported.
• Orthostatic hypotension and syncope. These drugs may lead to sudden drops in blood pressure and dizziness, particularly at the beginning of treatment.
• Falls. Antipsychotics may cause sleepiness, low blood pressure, and motor and sensory instability, which may lead to falls that can cause fractures or other injuries.
• Leukopenia, neutropenia, and agranulocytosis. Patients with a history of a low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy.
• Seizures. Atypical antipsychotics can lower the seizure threshold.

Contraindications (Who Should Not Take These Medications)

Contraindications may vary according to specific medication, but following are general guidelines for drugs in this subtype. 

People with any of the following in their history should not use atypical antipsychotics: 

• Known hypersensitivity. Patients with known hypersensitivity (allergy) to any component of the drug should not use it.
• Patients with a history of severe allergic reactions. Those with severe allergic reactions to any of the components of the drug formulation should avoid it.
• Use together with drugs known to cause QT prolongation or electrolyte imbalance. These drugs should not be used together as they can increase the risk of heart rhythm problems.
• Conditions where central nervous system depression is harmful. Such conditions include coma or severe CNS depression.
• History of agranulocytosis or severe neutropenia with a previous antipsychotic. Patients with this history should not use these drugs.
• Severe liver impairment. Certain atypical antipsychotics should not be used in patients with severe liver impairment.
• Diagnosis of a prolactin-dependent tumor. Patients with a prolactinoma should not use some atypical antipsychotics due to the risk of increased serum prolactin levels.
• Interactions with other drugs. These drugs can react with other medications, so always check with a doctor or pharmacist before starting anything new. See more about drug interactions below. 

The list above is meant as a general guide only and will vary according to the specific medication you’re taking. Only your doctor can decide if the benefits outweigh the risks for any medication based on your personal history.

Side Effects

Like the antipsychotic medications in the typical group, atypical antipsychotics can also have significant side effects. The list below is not a complete list of potential side effects, and not all of these occur with all atypical antipsychotics. 

• Weight gain. Atypical antipsychotics are known to cause weight gain in many individuals, and this can be associated with increased risks for diabetes and cardiovascular disease.
• Sedation. Similar to typical antipsychotics, atypical ones can also cause sedation or drowsiness.
• Anticholinergic effects. Atypical antipsychotics can have a drying effect and cause various side effects such as dry mouth, blurred vision, and constipation.
• Orthostatic hypotension. These medications may cause a drop in blood pressure with standing, leading to dizziness or fainting.
• Metabolic syndrome. This group of conditions includes increased blood pressure, high blood sugar levels, excess body fat around the waist, and abnormal cholesterol levels.
• Increased cholesterol. Atypical antipsychotics can raise cholesterol levels, which may contribute to heart disease.
• Seizures. Some atypical antipsychotics may lower the seizure threshold, leading to an increased risk of seizures.
• Hyperprolactinemia. Elevated levels of prolactin can occur, leading to symptoms such as breast enlargement, production of breast milk, and menstrual disturbances.
• Diabetes. These medications can increase blood sugar levels, sometimes leading to the development of type 2 diabetes.
• Cataracts. Particularly with quetiapine, there is some evidence to suggest an association with the development of cataracts.
• Agranulocytosis. Atypical antipsychotics, especially clozapine, can cause a drop in white blood cell count, leading to agranulocytosis, a white blood cell disorder.
• Cardiovascular conditions. Clozapine has been associated with myocarditis (inflammation of the heart muscle) and cardiomyopathy (disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body).
• Venous thromboembolism (VTE). There is an increased risk of blood clots in the veins with atypical antipsychotic use.
• Pulmonary embolism. As a part of VTE, pulmonary embolism can occur, which is a blockage in one of the pulmonary arteries in the lungs.
• Sudden cardiac death. Atypical antipsychotics have been linked to an increased risk of sudden cardiac death due to arrhythmias, or irregular heart rates.

Consult with your healthcare provider to learn about additional common and serious side effects specific to the medication you’re taking.

Drug Interactions

• CNS depressants. Taking atypical antipsychotics with other medications that cause drowsiness, like sleeping pills (Ambien) or anxiety medications (Xanax), can make you extra drowsy or even dangerously slow down your breathing.
• Blood pressure medications. If you’re taking drugs for high blood pressure, adding an atypical antipsychotic might cause drops in blood pressure, causing faintness or dizziness. 
• Parkinson’s disease treatments. Medications for Parkinson’s disease, like Sinemet (a combination of levodopa and carbidopa), might not work as well if you’re also taking an atypical antipsychotic.
• Medicines that affect liver enzymes. Some drugs can affect how your body processes atypical antipsychotics. For example, St. John’s Wort can make the antipsychotic less effective, while grapefruit juice might increase side effects.
• Drugs with anticholinergic effects. Medications that dry you out or make it hard to urinate, like some antihistamines, like diphenhydramine (Benadryl) or bladder control meds, like oxybutynin (Ditropan), can have these effects increased when taken with atypical antipsychotics.
• Drugs for arrhythmia. Medications that affect your heart’s rhythm, like quinidine, when taken with atypical antipsychotics, can increase the risk of an irregular heartbeat, which can be serious.
• Blood thinners. If you’re on a blood thinner like warfarin (Coumadin), atypical antipsychotics could either increase or decrease its effects. You may need more frequent monitoring with blood tests.

Conclusion

Antipsychotic medications have been shown to help patients with psychosis live a more comfortable life. They are typically prescribed by a mental health provider or psychiatrist after a thorough evaluation of a patient, including their health history and a review of the potential side effects. 

However, given the risks and possible medication interactions, it’s essential to notify your provider of any side effects or reactions. Working closely with your healthcare provider will allow them to find the most effective treatment for your specific needs.

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This information is intended for general informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication.