Atypical antipsychotics: Uses, common brands, safety info

Atypical antipsychotics, sometimes referred to as second-generation antipsychotics, are a newer class of medications used in the treatment of schizophrenia, mania, and other related mental health disorders. The typical, first-generation antipsychotics, which were developed in the 1950s, were a huge pharmacological step in the treatment of psychosis-related disorders. 

Science and research continued to improve this class of medications, and by the 1990s, this second generation was formed. By developing drugs that affected a broader variety of neurotransmitter receptors, drug developers hoped to avoid the extrapyramidal side effects of the first-generation medications. This was a successful development, though the second generation has some adverse effects as well. We will discuss the mechanisms of action, safety, and side effects of atypical antipsychotics. 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 atypical antipsychotics?

Atypical antipsychotics are the second generation of antipsychotics developed to treat mental health disorders such as symptoms of schizophrenia, mania, Tourette’s syndrome, and bipolar disorder. First-generation antipsychotic drugs work almost exclusively through the dopamine 2 (D2) receptor. The second generation was developed to work through a variety of neurotransmitter receptor types with the hopes of improved tolerability, symptom control, and fewer side effects. The second-generation antipsychotics are available in forms including immediate and extended-release oral tablets, dissolving tablets, and long-acting injections. There are inherent risks with all drugs in the treatment of mental disorders, and successful treatment may require trials of different antipsychotic agents to find the right one which balances symptom control with side effects and quality of life.

How do atypical antipsychotics work?

The atypical antipsychotics do not have the relatively uniform mechanism of action of the first-generation conventional antipsychotics, such as chlorpromazine or haloperidol. Each drug in the second generation has a unique affinity for an array of receptor types. The primary receptor types involved are the dopamine and serotonin receptors, though alpha and histamine receptors are involved as well for many of the drugs. Each drug in the class has a different specificity for specific dopamine and serotonin receptor types. This variety in receptor affinity is responsible for what is thought to be a lower incidence of extrapyramidal symptoms (EPS) such as uncontrolled muscle movements, neck spasms, rapid heartbeats, sweating, and tremors. Atypical antipsychotics, however, are linked to a higher incidence of metabolic syndrome, a condition consisting of a cluster of diagnosed conditions such as high blood pressure, high blood sugar (blood glucose), excess body fat on the waistline, and abnormal cholesterol (lipid) levels. 

What are atypical antipsychotics used for?

The unique affinity of each second generation for neurotransmitter receptors leads to some variation in thor approved indications for use. Below you will find a general list of conditions antipsychotic drugs are used for with the individual drug agents approved for that use next to it. 

• Agitation (aripiprazole, olanzapine)

• Autistic disorder (aripiprazole)

• Bipolar depression (cariprazine, lurasidone, olanzapine)

• Bipolar disorder (aripiprazole, asenapine, cariprazine, olanzapine)

• Depression (aripiprazole, brexpiprazole, olanzapine)

• Mania (aripiprazole, asenapine, cariprazine, olanzapine)

• Parkinson’s disease psychosis (pimavanserin)

• Schizoaffective disorder (clozapine)

• Schizophrenia (aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine)

• Tourette’s syndrome (aripiprazole)

Who can take atypical antipsychotics?

Adults

Adult men and women can take atypical antipsychotic drugs. Adults with a history of hypersensitivity to other antipsychotics should avoid the use of another antipsychotic if possible. Most atypical antipsychotics are associated with an abnormal heart rhythm known as QT prolongation. Patients with pre-existing cardiac conditions should be monitored closely if atypical antipsychotics are deemed necessary. Most atypical antipsychotic drugs also carry a black box warning from the Food and Drug Administration (FDA) for their use in patients that have a history of dementia or suicidal ideation, and these conditions may become worse when you take these drugs. Doses may need to be adjusted in patients with impaired renal or liver function.

Seniors

The FDA places strong warnings against the use of atypical antipsychotics in elderly patients with behavioral or psychological symptoms of dementia (BPSD). There is an increased mortality rate in these patients, and their use is considered inappropriate and should be avoided. 

Children

Some atypical antipsychotics have limited approved uses in children. Similar to traditional antidepressants, antipsychotic drugs carry a black box warning for the increased risk of suicidal thoughts and ideations in children and young adults, especially in the early stages of therapy. If the use of an approved drug is deemed necessary, these patients should be monitored with extreme caution.

Are atypical antipsychotics safe?

Atypical antipsychotic recalls

• Apotex Corp.: Voluntary recall of Guanfacine due to trace amounts of quetiapine

• Teva Pharmaceuticals: Voluntary recall due to dissolution test failure

Atypical antipsychotic restrictions

Do not take atypical antipsychotics if you have a history of hypersensitivity to other antipsychotics.

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

Atypical antipsychotics are contraindicated in patients with Parkinson’s disease, with the exception of Nuplazid (pimavanserin). Nuplazid has no dopaminergic activity, unlike all other second-generation antipsychotics, and is approved only for use in Parkinson’s disease psychosis (PDS). 

Atypical antipsychotics 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. They should also 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.

If you have a history of cardiovascular diseases such as arrhythmias, uncontrolled blood pressure, or chest pain, you should tell your clinician before being prescribed an atypical antipsychotic. Many of these drugs may cause an irregular heart rhythm known as QT prolongation, and pre-existing cardiac disease is one of the risk factors for QT prolongation.

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

Clozapine use is associated with a rare but fatal side effect of agranulocytosis, also called neutropenia, or a deficiency of white blood cells, leaving patients at an increased risk of dangerous infection. Regular blood monitoring is necessary, and for this reason, it is generally reserved only for patients who have disorders resistant to other drug choices.

In most cases, abrupt discontinuation of psychotropic medications is not appropriate. Your doctor will tailor a plan to taper you off of your medication if discontinuation is necessary to avoid the adverse events associated with abrupt discontinuation.

Are atypical antipsychotics controlled substances?

No, atypical antipsychotics are not controlled substances.

Common atypical antipsychotics side effects

The potential side effects of atypical antipsychotic medications vary a great deal in type and severity. Some are transient and short-term and will go away with time, while others can impede daily living and quality of life. Your doctor or pharmacist can discuss the prevalence of these side effects in more detail for a specific drug in the class.

• Difficulty concentrating or speaking

• Changes in blood pressure (hypertension or hypotension)

• Constipation

• Insomnia or difficulty sleeping

• Drooling

• Drowsiness or fatigue

• Headache

• Restlessness

• Sedation

• Sexual dysfunction

• Shuffling walk or gait 

• Tremor

• Blurred vision or double vision

• Metabolic syndrome

• Akathisia

• Hyperglycemia

• Weight gain

• Elevated liver enzymes

How much do atypical antipsychotics cost?

The second-generation antipsychotics are a relatively new class of drugs, with some members of this class hitting the market just in the last few years. There are some drugs in the class which have become available generically. SingleCare can help you save up to 80% off of the cost of your medications without insurance. Insurance coverage and formulary inclusion for each drug will vary by plan. Your pharmacist can help you find the best possible price, especially if you present your SingleCare discount card. 

This class has a broad range of pricing. For example, a month of standard dosing of Seroquel averages about $200 with no other coverage. With your SingleCare Seroquel coupon, you can get one month of the generic for $9. In contrast, Vraylar is not yet available generically. Without insurance, it may cost up to almost $1800. A Vraylar coupon will bring the price as low as $1165, and while that is a significant savings, it may still be cost-prohibitive for some without sufficient insurance coverage. If your doctor is thinking of prescribing an antipsychotic for your condition, check SingleCare for your best price.