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First- and Second-Generation Antipsychotics for Schizophrenia

Medically Reviewed by Jennifer Casarella, MD on May 12, 2022

If you have schizophrenia, your doctor will likely prescribe antipsychotic medication to help you manage symptoms like delusions and hallucinations.

Antipsychotics primarily block the effects of dopamine. Dopamine is a chemical that carries messages from one part of your brain to another. One theory is that if your dopamine levels are too high, it may contribute to psychosis.

There are two types of antipsychotic medications: first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs). FGAs were developed in the 1950s. SGAs came later, in the 1980s.

What’s an FGA?

First-generation antipsychotics are also called typical antipsychotics. They mostly block your dopamine receptors to help with symptoms. Doctors also prescribe FGAs for other mental health conditions, like acute mania, agitation, and bipolar disorder.

FGAs include:

  • Chlorpromazine (Thorazine)
  • Fluphenazine (Prolixin)
  • Haloperidol (Haldol)
  • Loxapine (Loxitane)
  • Perphenazine (Trilafon)
  • Pimozide (Orap)
  • Thiothixene (Navane)
  • Trifluoperazine (Stelazine)

What’s an SGA?

Second-generation antipsychotics, which are newer than FGAs, are also called atypical antipsychotics. That’s because they don’t work exactly like typical antipsychotic medications. They partially block your dopamine receptors and may affect other things, like serotonin.

SGAs include:

  • Aripiprazole (Abilify)
  • Asenapine (Saphris)
  • Clozapine (Clozaril)
  • Iloperidone (Fanapt)
  • Lurasidone (Latuda)
  • Olanzapine (Zyprexa)
  • Paliperidone (Invega)
  • Risperidone (Risperdal)
  • Quetiapine (Seroquel)
  • Ziprasidone (Geodon)

What’s the Difference Between FGAs and SGAs?

The biggest difference between FGAs and SGAs involves side effects.

FGAs tend to affect your body movement more than SGAs. They may cause movement problems like muscle stiffness. They may lead to more serious movement disorders.

SGAs are less likely to affect your body movement but more likely to lead to weight gain and metabolic changes.

What Are the Side Effects of FGAs and SGAs?

Your antipsychotics may have side effects. But everyone’s different, and not all antipsychotics affect people in the same way.

Generally, side effects from antipsychotics may include:

  • Blurred vision
  • Constipation
  • Dry mouth
  • Higher risk of diabetes
  • Hyperprolactinemia, which can lead to breast enlargement
  • Restlessness
  • Sexual problems
  • Sleepiness
  • Slowness
  • Uncontrollable movement or shakiness in your jaw, lips, and tongue (called tardive dyskinesia)

FGA side effects. One of the most significant side effects of FGAs is movement problems. They may be short-term or long-term. They may be moderate, like muscle stiffness, or they may develop into serious movement disorders.

Side effects of FGAs include:

  • Muscle stiffness
  • Dystonia
  • Tardive dyskinesia

Dystonia is a disorder where your muscles contract involuntarily and cause repetitive or twisting movements. You may have mild or severe muscle spasms that may be painful and interfere with your day-to-day life.

Tardive dyskinesia involves uncontrollable movement or shakiness in your jaw, lips, and tongue. If you have symptoms of tardive dyskinesia, your doctor may lower your dose of medication. But it’s possible you may need a higher dose. If so, your doctor may treat tardive dyskinesia with additional medications.

SGA side effects. SGAs are less likely to lead to movement problems. The most common side effects are weight gain and metabolic changes.

Side effects of SGAs include:

  • Diabetes
  • Hyperglycemia (high blood sugar)
  • Insulin resistance
  • Lipid abnormalities
  • Weight gain

Your doctor may recommend diet changes, exercise, or other medical treatments to offset these side effects.

How Well Do FGAs and SGAs Work?

Some studies show that FGAs and SGAs have about the same level of effectiveness in controlling symptoms of schizophrenia. They also suggest both types offer about the same quality of life.

But results aren’t conclusive and may vary. Some medications work better for some people than others. Their side effects may be different for different people. And some may be more tolerable than others, depending on the person.

Different medications within each category may have different levels of effectiveness. Not all FGAs have the same results. And not all SGAs are equal.

Some studies suggest certain SGAs may be better than other SGAs and better than FGAs. In a study at Oregon Health and Science University, researchers found that three SGAs may be the most effective medications for treating schizophrenia: clozapine (Clozaril), olanzapine (Zyprexa), and risperidone (Risperdal). The potential side effects of these medications may determine whether they’re right for you.

Which Antipsychotic Medication Is Right for Me?

Your psychiatrist will work with you to find the best medication for you. It may be an FGA or an SGA.

If you’ve had thoughts of suicide or you have treatment-resistant schizophrenia, your doctor may try the SGA clozapine (Clozaril). It’s the only antipsychotic medication that’s FDA-approved to treat refractory schizophrenia. It’s also the only antipsychotic medication shown to reduce suicidal thoughts. But there are risks, so your doctor will weigh the risks and benefits.

Your doctor will try to balance effectiveness and risk of serious side effects. For example, they may look at your response to a medication and how much risk you have of developing a movement disorder or metabolic problems. They’ll also consider your priorities, history, and all of your medical and psychiatric issues.

It may take time to find a medication that you tolerate well. You may start taking one medication, then try another if it doesn’t work well for you.

You may also think about cost when choosing a medication. The price of antipsychotics can be as low as $5 per month or as high as $2,000 or more every month. You can choose a generic instead of a name brand to bring costs down.

What If You Don’t Take Your Antipsychotics or Your Symptoms Don’t Go Away?

If you stopped taking your medication because of side effects or if you feel like your medication isn’t doing what you’d like, talk to your doctor. You may need a different type of medication that works better for you.

If you’re thinking about stopping your medication, talk to your doctor. It’s important not to stop suddenly. It’s also important to talk to your doctor about other medications you’re taking, including natural remedies, because they may interact with your antipsychotic medication.

Staying on your medication is important and has been shown to lead to a longer life. You’re less likely to stay on track with your medication if it doesn’t feel right, so it may be helpful to try another medication that feels better. You and your doctor may need to reevaluate your medication on a regular basis.

If you are having thoughts of suicide, or you’re worried about a friend or loved one, someone is available 24 hours a day, every day at the National Suicide Prevention Lifeline. Call 800-273-8255.

Show Sources

SOURCES:

American Family Physician: “How do we select an antipsychotic for those with schizophrenia?”

Expert Opinion on Pharmacotherapy: “Schizophrenia.”

Psychiatric News: “Which Antipsychotics Are Best for Your Patients?”

Agency for Healthcare Research and Quality: “First-Generation Versus Second-Generation

Antipsychotics in Adults: Comparative Effectiveness [Internet].”

Mayo Clinic: “Dystonia.”

National Alliance on Mental Illness: “Schizophrenia.”

Rethink Mental Illness: “Antipsychotics.”

National Suicide Prevention Lifeline.

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