First-Generation (Typical) Antipsychotics

First-generation antipsychotic drugs target symptoms known as positive symptoms of schizophrenia. These symptoms include hallucinations and delusions. First-generation antipsychotic drugs are also called typical antipsychotics.^1-3

The term “first-generation” is often used because a newer class of drugs has been developed since these drugs were first developed. The newer drugs are called second-generation, or atypical, antipsychotics. Second-generation antipsychotics do not cause some of the side effects that first-generation drugs do. They may also work better at treating episodes of psychosis.^1-4

First-generation drugs are still used often. But most people who have schizophrenia with psychosis will be prescribed a second-generation drug before a first-generation drug is used.¹

How do first-generation antipsychotics work?

First-generation antipsychotics affect neurotransmitters in the brain. Neurotransmitters are chemicals that the brain uses to send messages. Antipsychotics reduce the action of a neurotransmitter called dopamine in the brain.²

They do this by targeting a receptor called the dopamine-2 receptor. For this reason, they are also called dopamine-2 blockers. But the drugs affect other receptors, too. These targets affect neurotransmitters like acetylcholine. This action can lead to unwanted side effects that are not related to schizophrenia symptoms.^1-3,5

These drugs are used to treat episodes of severe agitation, bipolar disorder, and other mental health issues in addition to schizophrenia. But they do not work for everyone. As many as 1 in 3 people taking a first-generation antipsychotic will not have a strong response to it. This is another reason why second-generation drugs are used more often.^1,5

Examples of first-generation antipsychotics

There are many first-generation antipsychotic drugs. They include:¹

• Fluphenazine
• Haloperidol
• Loxapine
• Perphenazine
• Pimozide
• Thiothixene
• Trifluoperazine
• Chlorpromazinev
• Thioridazine

These drugs come in a variety of forms. Some come as tablets or liquids. Others can be given through an injection into the muscle.¹

The exact drug your doctor prescribes will depend on your preferences, your previous experience with antipsychotic drugs, and a drug’s potential side effects. You and your doctor will work together to find a drug that has the best dosing schedule and form for you. For example, you may prefer to take a daily pill rather than an injection every few weeks.

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Common side effects of first-generation antipsychotics include:^1-3,5,6

• Sleepiness
• Dizziness, especially when standing up
• Feeling restless
• Fast heartbeat or irregular heartbeat
• Blurry vision
• Dry mouth
• Constipation

Extrapyramidal symptoms

One group of side effects that can come along with first-generation drugs are related to movement. These side effects are called extrapyramidal symptoms (EPS). EPS can look similar to Parkinson’s disease. This is because both Parkinson’s disease and first-generation antipsychotics affect dopamine. These symptoms are important to avoid because they can affect daily activities.^2,3,5

Examples of EPS include:^1-3,5,6

• Restlessness and inability to stay still (akathisia)
• Uncontrolled facial, mouth, jaw, or tongue movements (tardive dyskinesia)
• Tremors or other symptoms similar to those of Parkinson’s disease (like rigid muscles)
• Moving very slowly (bradykinesia)

If you notice any of these issues, talk with your doctor as soon as possible. There may be potential treatment options. However, EPS can be permanent if not addressed.²

These are not all the possible side effects of first-generation antipsychotics. Talk to your doctor about what to expect when taking antipsychotics. You also should call your doctor if you have any changes that concern you when taking these drugs.

Other things to know

If you are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed, talk with your doctor. Some antipsychotic drugs may not be safe to take while pregnant or breastfeeding.³

First-generation antipsychotics can have strong interactions with other drugs. Before beginning treatment for schizophrenia, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.¹

Sticking to a treatment plan is important for managing the symptoms of schizophrenia. This is called having good treatment adherence. When you skip doses or stop drugs on your own, symptoms of psychosis can return. If you are having trouble getting prescribed drugs, accessing healthcare, or sticking to your plan, talk with your healthcare team. They will work with you to help you find a solution that makes things easier.⁵