What are the least sedating antipsychotics?

Key takeaways

• Like any medication, antipsychotics have some risk of side effects, including fatigue, drowsiness, or sedation. However, some types of antipsychotics are more likely to have this risk than others.
• There are two main classes of antipsychotics: typical and atypical. Atypical antipsychotics are the ones that are less likely to have sedating effects.
• The injectable forms of certain typical antipsychotics may also be less likely to cause sedation than the oral tablet forms.

Overview

Antipsychotics help treat mental health conditions like bipolar disorder and schizophrenia. They work by altering your brain chemistry and easing symptoms such as hallucinations and delusions. A doctor may also recommend antipsychotics for other conditions.

There are two types of antipsychotic medications:

• Typical antipsychotics: These were the first antipsychotics developed and include medications such as:
  • haloperidol (Haldol)
  • perphenazine (Trilafon)
  • pimozide (Orap)
• Atypical antipsychotics: These are newer antipsychotics that might cause fewer side effects. Atypical antipsychotics include:
  • aripiprazole (Abilify)
  • asenapine (Saphris)
  • lurasidone (Latuda)
  • palipedirone (Invega)

Typical and atypical (also known as first-generation and second-generation) antipsychotics commonly cause drowsiness. Some also cause sedation. Generally, atypical antipsychotics are less likely to cause sedation (and other side effects) than typical antipsychotics.

Need a diagnosis or prescription quickly? Optum Perks offers personalized on-demand care in as little as 15 minutes. For $29, answer a few questions online and receive a diagnosis and treatment plan from a US-licensed healthcare professional. Get started here.

Least sedating antipsychotics

Although many antipsychotics typically cause drowsiness as a side effect, some are less likely to cause sedation than others.

Haloperidol decanoate (Haldol) injection

Haloperidol (Haldol) is a typical antipsychotic. This medication can help you manage symptoms like hallucinations and delusions. Haloperidol is available as an oral tablet, or another version is available as an injection that you receive once every 4 weeks. This version is called haloperidol decanoate (Haldol 50).

Although typical antipsychotics are usually more likely to cause sedation than atypical ones, one 2021 review examining the side effects of 37 different antipsychotics concluded that the long-acting haloperidol decanoate injection was unlikely to cause drowsiness. 

Although the injectable form of this medication is unlikely to cause sedation, the review found that the pill form has strong associations with sedation. Some people may find it easier to have 4-weekly injections of this medication, as they won’t have to remember to take tablets daily.

The haloperidol injection is less likely to cause drowsiness than other antipsychotics. However, it may cause other side effects like:

• dry mouth
• changes to the menstrual cycle
• constipation
• weight gain
• erectile dysfunction

If you need help covering the cost of medications, the free Optum Perks Discount Card could help you save up to 80% on prescription drugs. Plus, you can now get them delivered to your home in as little as 3 days. Search for your medication here.

Paliperidone (Invega)

Paliperidone (Invega) is an atypical antipsychotic. It can improve your mood by rebalancing the feel-good chemicals dopamine and serotonin in your body. A 2021 review found that paliperidone was one of the medications least likely to cause sedation.  

Even though the medication has a low risk for drowsiness, some other side effects of the medication can include:

• tremors and shaking
• irregular eye movements
• constipation
• weight gain
• heartburn
• sore throat

Aripiprazole lauroxil (Abilify Maintena) injection

Aripiprazole (Abilify) is also an atypical antipsychotic. The same 2021 review found that the injection form of Abilify was less sedating than the pill form.

While the medication can improve your mood, reduce hallucinations, and help you concentrate, it can still cause side effects such as:

• dizziness
• blurred vision
• tremors and shaking
• skin discoloration or pain at the injection site

Other antipsychotics

A 2019 review found that low risk antipsychotics for drowsiness also include:

• perphenazine (Trilafon)
• fluphenazine (Prolixin)
• cariprazine (Vraylar)

A 2019 review and meta-analysis of antipsychotic side effects found that pimozide (Orap) was the antipsychotic medication least likely to cause sedation.

The 2021 review noted that the variety of sedating effects between participants could result from:

• drug–gene influences
• drug–drug interactions (DDI)
• a combination of both

Most sedating antipsychotics

Although many people seek to avoid the sedating effects of antipsychotics, some people find that the sedating effects of antipsychotics can help them sleep, so they aim to take them before going to bed.

Several antipsychotics can increase the risk of drowsiness and may be best for sleep. Examples include:

• clozapine (Clozaril)
• zuclopenthixol (Clopixol)

The 2019 review of antipsychotics found zuclopenthixol to be the most likely to cause sedation.

When to speak with a doctor

Each medication can affect people differently. Some people may find that the drowsiness their medication causes helps them sleep. But you may find that feeling drowsy gets in the way of your day-to-day life and makes you more vulnerable to accidents.

If your medication makes you particularly drowsy, talking with a doctor about this can help. They may be able to recommend an alternative.

Summary

Antipsychotics can cause drowsiness as a side effect.  Everyone responds differently to medication, but some of the least sedating antipsychotics may include:

• haloperidol decanoate (Haldol), in injection form
• paliperidone (Invega), in pill form
• aripiprazole lauroxil (Abilify Maintena), in injection form

Certain antipsychotics, such as zuclopenthixol (Clopixol) and clozapine (Clozaril), may be more likely to make you feel drowsy.

If you have noticed that your medication is making you drowsy and interfering with your day-to-day life, talking with a doctor might help. They may adjust your medication dose or suggest that you try other medication options.

It’s important to read the information included with your medication carefully. Some antipsychotics may cause a high level of drowsiness, so you should avoid certain activities, such as driving.

Download the free Optum Perks Discount Card to save up to 80% on many prescription medications. Plus, you can now get them delivered to your home in as little as 3 days. Search for your medication here.