Lybalvi: A Dual-Action Treatment for Schizophrenia and Bipolar I Disorder

Medically Reviewed by Joanne Nguyen, PharmD, BCACP on July 28, 2024
11 min read

Schizophrenia and bipolar I disorder are two conditions that have many differences between them. A class of medicines called antipsychotics can be used to treat both conditions but may cause unwanted side effects such as weight gain. 

Lybalvi (lee bawl' vee) was approved in 2021 for the treatment of schizophrenia, alone for short-term or ongoing treatment (maintenance treatment) of manic or mixed episodes of bipolar I disorder, or with valproate or lithium to treat manic or mixed episodes of bipolar I disorder.

Schizophrenia is a mental health condition that affects the way that a person thinks, acts, feels, or interacts with others. People with schizophrenia may have problems at work, in social settings, or in school. The severity of schizophrenia is different from person to person. There is no cure, but symptoms can be managed with medicines.

Bipolar disorder is a condition that causes severe changes in mood and energy that can cause unpredictable high (manic), low (depressive), and mixed (both high and low) mood swings. There are two types of bipolar disorders: bipolar I and bipolar II. A person with bipolar I has had at least 1 episode of mania (also called a manic episode). There is no cure for bipolar disorder, but medicines are used to help control symptoms and improve quality of life. 

Lybalvi contains two medicines: olanzapine, which is an atypical antipsychotic, and samidorphan, which is an opioid antagonist that reduces the risk of weight gain caused by olanzapine. Olanzapine works to block certain receptors in the brain, including those for serotonin and dopamine. This in turn balances these chemicals. Samidorphan works to block opioid receptors in the brain, which can help lower the weight gain normally seen with olanzapine. 

Lybalvi is taken once a day with or without food. It is important not to split the tablet or combine multiple doses of Lybalvi. Lybalvi is available in 4 doses: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg. Take Lybalvi as prescribed by your health care provider. 

The dose your health care provider starts you on may be different, depending on what condition you have (either bipolar I or schizophrenia) and if you are taking Lybalvi by itself or with other medicines. Your health care provider may also start you on a dose of Lybalvi and either increase or decrease your dose, depending on how you tolerate the medicine. 

Two studies were done in people with schizophrenia to look at the safety and efficacy of Lybalvi. 

The first study looked at the change from baseline to week 4 in the PANSS total score. The PANSS scale is a screening tool, with a higher score meaning schizophrenia symptoms are more severe. People in the study either received Lybalvi, olanzapine (which is an antipsychotic), or a placebo containing no medicine. People in the study were 18 to 70 years old, with the average age being 41 years old. 

The second study looked at the change in body weight and the number of people who had at least a 10% weight gain from baseline to week 24. People in the study received either Lybalvi or olanzapine. They were 18 to 55 years old, with 82% being 30 years of age or older and 60% having a body mass index (BMI) of less than 27. 

Olanzapine as the only medicine for bipolar I disorder

Olanzapine is one of the two medicines in Lybalvi. For the clinical studies discussed below, olanzapine was observed to see how it would affect people with bipolar I disorder.

Two studies were done to look at people who took only olanzapine (an antipsychotic) for their bipolar I disorder, compared to a placebo. The studies used the Young Mania Rating Scale (YMRS), which looks at the degree of manic symptoms based on an 11-point scale. The higher the score, the more severe the manic symptoms. People in the studies had either manic or mixed episodes of bipolar I and were 18 to 70 years old. One study was done over 3 weeks and the other over 4 weeks.

Another study was done in people who were in remission from a manic or mixed episode. The study looked at the time it took for people to relapse into a mood episode, which was based on the YMRS score, Hamilton Depression Rating Scale (HAM-D) score (which looks at depression symptoms), or hospitalization. Relapse in bipolar I is the return of bipolar I symptoms after a period of time of having little to no symptoms. People in the study were 18 years or older, with the average age being 39 to 41 years old. People in the study received either olanzapine or a placebo for up to 48 weeks.

Olanzapine plus other medicines for bipolar I disorder

The study looked to see if olanzapine plus valproate or lithium was better at improving bipolar I symptoms, compared to using valproate or lithium alone. The YMRS score was used to look at this. People in the study had bipolar I with manic or mixed episodes and were taking valproate or lithium for at least 2 weeks. The average age of people in the study was 40 to 41 years, and more than half of the people in the study were taking valproate (around 65%).

The studies included people who were White Americans, African Americans, Asian Americans, and those classified as “Other,” where no race was specified. 

Schizophrenia:

  • People who took Lybalvi had a better PANSS score, compared to those who took a placebo, but had a similar score when compared to those on olanzapine. This means that people who took Lybalvi had an improvement in their schizophrenia symptoms. 
  • The group that took Lybalvi had less weight gain and fewer people who gained 10% or more weight, compared to those on olanzapine. This means that people who took Lybalvi had less weight gain.

Bipolar I: 

  • People who took olanzapine had lower YMRS scores, compared to those who took a placebo. This means that people taking olanzapine had improved manic or mixed symptoms, compared to those on the placebo.
  • People who took olanzapine also had delayed relapsed times, when compared to those on the placebo. This means that olanzapine helped people stay in remission and have little to no bipolar I symptoms for a longer period of time.
  • People who took olanzapine with either valproate or lithium had lower YMRS scores, compared to those who just took valproate or lithium. This means that people taking olanzapine with lithium or valproate had more improved symptoms of manic or mixed episodes.

In clinical studies, Lybalvi started working in as little as a few weeks. The time it takes for Lybalvi to work may be different for you if your health care provider has to adjust your dose when you first start taking the medicine. Lybalvi is working when you start to see fewer manic or mixed episodes if you have bipolar I, or fewer symptoms if you have schizophrenia. If it has been a few months and your bipolar I or schizophrenia symptoms have not improved, talk to your health care provider. Your health care provider may increase your dose, add on another medicine, or change you to a new medicine. 

Depending on if you are taking Lybalvi for schizophrenia or bipolar I disorder or if you are taking Lybalvi by itself or with lithium or valproate for your bipolar I symptoms, the side effects may be different. 

If you are taking Lybalvi for schizophrenia, the common side effects are listed below.

  • Weight gain
  • Drowsiness (or sleepiness)
  • Dry mouth
  • Headache

If you are taking Lybalvi by itself for bipolar I disorder, the common side effects are listed below.

  • Feeling unusually weak or tired
  • Dry mouth
  • Constipation
  • Increased appetite
  • Drowsiness (or sleepiness)
  • Dizziness
  • Shaking

If you are taking Lybalvi with other medicines such as valproate or lithium for bipolar I disorder, the common side effects are listed below.

  • Dry mouth
  • Upset stomach (or indigestion)
  • Weight gain
  • Increased appetite
  • Dizziness
  • Back pain
  • Constipation
  • Problems speaking
  • Mouth watering (drooling)
  • Memory problems
  • Numbness and tingling in your arms and legs

Taking Lybalvi can change your metabolism, which can cause an increase in appetite, weight, and blood sugar and cholesterol levels. Your health care provider may monitor your weight and may also monitor your sugar and cholesterol levels while taking Lybalvi.

Lybalvi can cause you to feel drowsy, unusually tired, and dizzy. Do not drive or operate heavy machinery until you know how Lybalvi affects you

You can have dry mouth when taking Lybalvi. There are certain things that you can do to help lessen this, including sipping water regularly, using a humidifier, breathing through your nose instead of your mouth, and limiting caffeine and sugar-free gum.

If you are having headaches because of Lybalvi, taking over-the-counter medicines such as acetaminophen or ibuprofen can help. Talk to your health care provider if your headaches do not go away or if they are getting worse. 

Constipation can happen as a result of taking Lybalvi. If you get constipation, drinking plenty of water, eating fiber (as a supplement or from food), and exercising regularly can help manage your symptoms. Avoiding high-fat foods such as meats and cheeses may help. Talk to your health care provider if you can’t have a bowel movement. Your health care provider may recommend over-the-counter medicines that can help, which can include stool softeners, fiber supplements, or laxatives. Tell your health care provider about all the medicines that you take. Certain medicines can cause constipation and, if taken with Lybalvi, may make constipation worse. Food with higher fiber content is listed below.

  • Fruits
  • Vegetables
  • Beans
  • Brown rice
  • Bran cereal

Talk to your health care provider if you are having the shakes due to Lybalvi. Your health care provider may lower the dose of your medicine, prescribe you medicine to treat your symptoms, or switch you to another medicine.

Taking Lybalvi can cause an upset stomach, also known as indigestion or dyspepsia. You may have discomfort or pain in your stomach, feel full too soon while eating, feel uncomfortable after eating, feel bloated or nauseated, have gas, or have heartburn. Taking Lybalvi with food, avoiding alcohol, caffeine, or spicy foods, and taking over-the-counter medicines such as Tums, Pepcid, or Prilosec can help with indigestion symptoms. Talk to your health care provider if your indigestion symptoms do not improve or get worse. 

If you have back pain as a result of Lybalvi, talk to your health care provider about how to best manage this.

Talk to your health care provider if you have trouble speaking, have issues with excessive drooling, memory problems, or numbness or tingling in your arms or legs. Your health care provider will advise you on how to manage these side effects or make changes to the medicines you are taking.

Tell your health care provider if you are taking a medicine that has olanzapine in it. One of the medicines in Lybalvi is olanzapine, and taking a medicine that has olanzapine in it with Lybalvi may increase your risk of side effects.

Lybalvi should not be used in people who are currently taking an opioid medicine or who have recently stopped taking an opioid medicine and are going through withdrawal. Opioid withdrawal happens when you stop taking opioids after your body has become reliant on them. This can cause a wide range of side effects that affect your body. Talk to your health care provider if you have stopped taking an opioid in the past 14 days. One of the medicines in Lybalvi is samidorphan, which can cause severe opioid withdrawal that could cause you to go to the hospital.

Other medicines affecting Lybalvi

There are specific medicines that can affect the blood levels of Lybalvi. These medicines can either cause Lybalvi to not work as well or increase your risk of side effects. Tell your health care provider about all the medicines you are taking. Your health care provider will determine if you are taking any medicines that interact with Lybalvi, and they may make changes to the medicines you are taking or change the dose of Lybalvi you are taking.

Taking Lybalvi with alcohol; a medicine called diazepam, which is used for anxiety, seizures, and muscle twitching; or other medicines that affect your nervous system can increase your risk of having a sudden dip in blood pressure, also known as orthostatic hypotension. Tell your health care provider about all the medicines you are taking. Your health care provider will determine if you are taking a medicine that affects your nervous system.

Taking Lybalvi with an anticholinergic medicine can slow down the movement of food in your body. An anticholinergic medicine blocks the activity of acetylcholine, which is a chemical that communicates information between cells in the body. Anticholinergic medicines can include antihistamines (such as Benadryl), and medicines used to treat overactive bladder, Parkinson’s disease, or stomach problems. Tell your health care provider about all the medicines you are taking. Your health care provider will determine if you are taking an anticholinergic medicine.

Lybalvi affecting other medicines

Lybalvi may increase the effects of blood pressure-lowering medicines. Your health care provider may monitor your blood pressure while you are on Lybalvi and may lower the dose of your blood pressure medicine if needed.

Lybalvi may stop the effects of levodopa and dopamine agonists, which are medicines commonly used in Parkinson’s disease. It is not recommended to take Lybalvi with levodopa or dopamine agonists.

Lybalvi can affect your urine drug test results. Tell those giving the drug screening test that you are taking Lybalvi.

Lybalvi can cause drowsiness, dizziness, and tiredness. Do not drive or operate heavy machinery until you know how Lybalvi affects you.

There is a copay savings card from the drugmaker that may allow you to pay as little as $0 for your first three fills. After those fills, you may be eligible to pay as little as $20 for each 30-day supply. Whether you are eligible depends on the type of insurance you have. You can find out more at www.lybalvi.com/bipolar-1-disorder/co-pay-savings-program or by calling 855-820-9624.