Antipsychotics explained

What antipsychotics are

Antipsychotics are a class of medication used to treat psychosis and several other conditions. The name points to psychosis, but it understates what they do. In psychiatric care they treat schizophrenia and bipolar disorder, and at lower doses several of them are added to antidepressants for depression that has been hard to treat.

There are two generations. The older first-generation antipsychotics are also called typical antipsychotics. The newer second-generation antipsychotics are also called atypical antipsychotics. The atypicals are the ones most used today in mood care, and they are the focus of this guide.

The main atypicals covered here are quetiapine (Seroquel), aripiprazole (Abilify), risperidone (Risperdal), olanzapine (Zyprexa), and lurasidone (Latuda).

How they work

Nerve cells in the brain pass messages using chemical messengers. Dopamine is one of them. Receptors are the docking points a cell uses to receive those messages. Antipsychotics act on dopamine receptors. The first-generation drugs mainly block dopamine activity. That blocking eases psychotic symptoms, but turning down dopamine across the brain is also what produces many of the movement side effects of the older drugs.

The second-generation antipsychotics act on dopamine receptors too, but they also act on serotonin receptors, another chemical messenger system. Some, such as aripiprazole, do not simply block dopamine. They dampen it in some places and modestly support it in others. These broader actions are thought to ease psychotic and mood symptoms while causing fewer movement problems than the older drugs. How exactly that translates into mood benefit is not fully understood, and it is worth being honest about that.

How the class developed

The first antipsychotics, now called first-generation or typical antipsychotics, arrived in the 1950s. Chlorpromazine came first, and it changed the treatment of psychosis. For the first time there was a medication that reliably reduced the symptoms of schizophrenia. Other typical antipsychotics followed through the 1950s and 1960s.

These drugs worked, but the strong dopamine blocking caused movement side effects in many people, including stiffness, tremor, and over time tardive dyskinesia. The second-generation, or atypical, antipsychotics arrived from the 1990s. They were developed to reduce those movement-related side effects. The atypicals did ease that particular problem for many people, but over the following years a different concern came into focus. Several of them, especially when used long term, cause weight gain and changes in blood sugar and cholesterol. Neither generation is free of trade-offs. The atypicals are now the more commonly used group, including in mood disorders.

What they are used for

Antipsychotics are used for several conditions.

• Schizophrenia and other psychotic conditions.
• Bipolar disorder, including manic episodes, bipolar depression, and ongoing maintenance treatment.
• As an add-on to an antidepressant in depression that has been hard to treat.

It is worth being clear about that last use. When someone sees an antipsychotic prescribed for depression, it is usually as a low-dose add-on to an antidepressant that has helped only partway. The dose used this way is well below a full antipsychotic dose. It does not mean the diagnosis has changed to psychosis. Adding an antipsychotic to boost an antidepressant is a recognized approach for depression that has not fully responded.

Some atypicals are also approved for other uses, such as irritability associated with autism. Those uses are outside the scope of this guide.

What they have in common

The medications in this class share a number of features.

• They take time to work for mood and psychotic symptoms. The fuller benefit builds over days to weeks, not the day a person starts.
• They carry an FDA boxed warning about an increased risk of death in older adults with dementia-related psychosis. A boxed warning is the most serious warning the FDA applies to a medication. Antipsychotics are not approved for dementia-related psychosis.
• Metabolic effects are a shared concern. This means weight gain and rises in blood sugar and cholesterol. Together these can raise the risk of diabetes, so weight and blood tests are monitored during treatment.
• Tardive dyskinesia, a movement disorder, is a risk with long-term use. It involves repetitive, involuntary movements, often of the face or mouth. Reporting any new movements early matters.
• Neuroleptic malignant syndrome, a rare but serious reaction, can occur. Signs include high fever, muscle stiffness, confusion, and an unstable heartbeat or blood pressure. It is a medical emergency.

When an atypical is used as an add-on for depression, a second boxed warning also applies, the one shared by antidepressant treatment about an increased risk of suicidal thoughts and behaviors in people under 25, especially early in treatment.

How they differ from each other

The antipsychotics in this group treat broadly overlapping conditions, so the choice between them is driven mostly by side effects.

Quetiapine is quite sedating. Most people feel that drowsiness quickly, and it is the reason quetiapine is sometimes used off-label at low doses for sleep. Quetiapine is also more associated with weight gain than some others in the group.

Aripiprazole is closer to the opposite. It tends to be activating rather than sedating, so trouble sleeping is one of its more common early effects, and it is often taken in the morning. It is generally lighter on weight. Its more notable side effect is akathisia, a feeling of restlessness and an inability to sit still.

Risperidone is effective and widely used, and it is more likely than some others to raise prolactin, a hormone. Olanzapine is effective but is among the most associated with weight gain and metabolic effects. Lurasidone is often noted for a lighter effect on weight and is taken with food.

How a prescriber chooses one

Because these medications are broadly similar in what they treat, the choice is usually about fit rather than raw strength. A prescriber weighs several things. One is the target symptom. Someone whose sleep is badly disrupted may do better with a more sedating option, while someone who is already slowed down may do better with a more activating one. Another is which side effects to avoid. Concern about weight and metabolic health may steer the choice away from the heavier options. Other medical conditions, other medications, and heart history all factor in.

Response is individual. A medication that did not suit one person may suit another, and a poor result with one antipsychotic does not predict the result with the next. Finding the right one, at the right dose, is often a process of adjustment with a prescriber.

The medications in this class

• Quetiapine (Seroquel). An atypical antipsychotic used across schizophrenia, bipolar disorder, and depression as an add-on. It tends to be sedating and is more associated with weight gain.
• Aripiprazole (Abilify). An atypical antipsychotic used in schizophrenia, bipolar disorder, and depression as an add-on. It tends to be more activating and lighter on weight, with akathisia as a notable side effect.
• Risperidone (Risperdal). An atypical antipsychotic used in schizophrenia and bipolar disorder.
• Olanzapine (Zyprexa). An atypical antipsychotic used in schizophrenia and bipolar disorder. It is effective but more associated with weight gain and metabolic effects.
• Lurasidone (Latuda). An atypical antipsychotic used in schizophrenia and bipolar depression, often noted for a lighter effect on weight.

PsychiatryRx has dedicated guides for quetiapine and aripiprazole, with more detail on uses, side effects, dosing, and what to expect.

Common questions

Why would an antipsychotic be prescribed for depression? When an antipsychotic is added for depression, it is usually a low-dose booster alongside an antidepressant that has helped only partway. The dose is well below a full antipsychotic dose. It does not mean the diagnosis is psychosis. Using an antipsychotic this way is a recognized approach for depression that has not fully responded.

Are antipsychotics dangerous? They are serious medications with real risks, including a boxed warning, metabolic effects, and movement-related concerns. That is why they are prescribed and monitored carefully. For many people with schizophrenia, bipolar disorder, or hard-to-treat depression, the benefit is meaningful, and untreated illness carries its own real risks. The point of monitoring is to catch problems early.

What is tardive dyskinesia? It is a movement disorder that can develop with long-term use of antipsychotics. It involves repetitive, involuntary movements, often of the face or mouth, such as lip smacking or tongue movements. The risk rises with longer use. New movements should be reported to a prescriber early.

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.

1. U.S. Food and Drug Administration. Prescribing information.
2. MedlinePlus, U.S. National Library of Medicine.
3. National Institute of Mental Health. Mental health medications.