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Comparing Lybalvi Vs Zyprexa: 3 Reasons to Opt for Lybalvi Over Olanzapine

Lybalvi Vs Zyprexa

Lybalvi Vs Zyprexa compares the Pros and Cons of Lybalvi, a fixed dose combination of Olanzapine and Samidorphan, Vs Zyprexa (Olanzapine) alone.

Lybalvi is a fixed-dose combination of Olanzapine and Samidorphan. It is available in different strengths as mentioned below [Ref]:

  • Olanzapine/ Samidorphan: 5/10 mg (Yellow capsule)
  • Olanzapine/ Samidorphan: 10/10 mg (Orange Capsule)
  • Olanzapine/ Samidorphan: 15/10 mg (Blue Capsule)
  • Olanzapine/ Samidorphan: 20/10 mg (Pink Capsule)

Symbyax is another fixed-dose combination of Olanzapine that contains Fluoxetine (Prozac) and Olanzapine.

Why Psychiatrists May Need To Choose Lybalvi Over Zyprexa:

Olanzapine is the main drug present in both pills, Lybalvi and Zyprexa. However, Lybalvi also contains Samidorphan which is an opioid antagonist.

The addition of Samidorphan to Olanzapine in a fixed dose has three major advantages over Olanzapine monotherapy:

  • Less weight gain
  • Better Glycemic Parameters, and 
  • Better Lipid Parameters.

Since obesity is a global pandemic. Weight gain is associated with multiple comorbid conditions including diabetes, hypertension, fatty liver, sleep apnea, and cardiovascular diseases, the addition of a drug to blunt the weight gain effects of Zyprexa is the need of the hour.

Lybalvi is a drug combination of Olanzapine and an opioid antagonist, Samidorphan. The combination is formulated to reduce the pill burden and simultaneously improve the metabolic abnormalities associated with Olanzapine.

Other options would have been adding a weekly GLP-1 analog such as Ozempic, or Mounjaro, or adding other opioid antagonists like Naltrexone.

It is also important that the combination should not affect the efficacy of Olanzapine. Here is a comparison of Lybalvi vs Zyprexa on the PANSS and CG-I score in patients with Schizophrenia.



Lybalvi Vs Zyprexa (Olanzapine): Which is Better

Although the addition of Samidorphan to Olanzapine is to reduce weight gain and improve the metabolic parameters associated with Olanzapine treatment, a change in the efficacy is one of the key deciding factors when prescribing Lybalvi instead of Zyprexa.

Efficacies in psychiatric conditions and especially schizophrenia are difficult to assess and are usually a subjective assessment rather than an objective one. Commonly the PANSS (positive and negative syndrome scale) psychopathology subscale and the CGI-S score are used to assess the efficacies of different antipsychotics.

The PANSS score has 3 major components: positive symptoms, negative symptoms, and general psychopathology scale. You can calculate your scores here: Positive and Negative Syndrome Scale for Schizophrenia (PANSS).

The CGI-S score is a single-point score to assess the overall severity of the condition [Ref]

lybalvi vs zyprexa panss score
PANSS Score: Lybalvi Vs Zyprexa [Source]
The proportion of PANSS Score responders at week 4 was significantly greater in the Lybalvi Vs Placebo (59.8%, P-value: 0.002) compared to Zyprexa vs Placebo (53.8%; P-value: 0.015) [Ref]. 

Lybalvi Vs Zyprexa (Olanzapine) CGI-S Score
Lybalvi Vs Zyprexa (Olanzapine) CGI-S Score [Ref]
The proportion of CGI-I responders at week 4 was significantly greater in the Lybalvi Vs Placebo (57.6%, P-value: <0.001) compared to Zyprexa vs Placebo (50.8%; P-value: 0.004) [Ref]

Although the study above demonstrated a slight superiority of Lybalvi vs Zyprexa, both drugs are generally considered equally effective in the treatment of Schizophrenia.

The only factor influencing the selection of Lybalvi Vs Zyprexa is the better metabolic parameters and less weight gain with Lybalvi Vs Zyprexa.



Lybalvi Vs Zyprexa (Olanzapine): Effect on Body Weight

One of the primary reasons for adding Samidorphan to Olanzapine in a fixed-dose combination is to reduce the olanzapine-associated weight gain.

Olanzapine has been associated with significant weight gain in adults and adolescents. The table below compares the effect of Olanzapine on body weight after 6 weeks [Ref]:

Weight gain



Weight gain⇑ 2.6 kg (5.7 lb)⇓ 0.3 kg (0.6 lb)
Greater than 7% weight gain22.2%3%

Samidorphan is an opioid antagonist. Like Naltrexone, it blocks the appetite centers in the brain suppressing appetite. Naltrexone, in combination with Bupropion, is approved by the FDA for weight loss. It is available under the brand name Contrave.

Naltrexone has been studied in small studies to evaluate its effectiveness in suppressing weight gain secondary to antipsychotics [Ref]. It was noticed that Naltrexone reduced cravings for sweets and induced weight loss in patients with schizophrenia who were gaining weight on antipsychotics [Ref]

Like Naltrexone, Samidorphan in the fixed-dose combination with Olanzapine is utilized to reduce Olanzapine-induced weight gain. Here is a table of comparison between Lybalvi and Zyprexa (Olanzapine) [Ref]


Weight gain

Significance value

Placebo0.8 kgP value 0.09
Samidorphan1 kg
Lybalvi (Samidorphan + Olanzapine)1.4 kgP value: 0.02
Olanzapine1.9 kg

From the table above, weight gain is obviously more in patients in the Olanzapine (Zyprexa) group compared to Lybalvi.

In addition to its weight loss and appetite suppressant effects, the addition of Samidorphan to Olanzapine (Lybalvi) also resulted in a better metabolic profile including lipids and blood glucose.



Lybalvi Vs Olanzapine: Effects on Metabolic Parameters:

Olanzapine (Zyprexa) is associated with abnormal metabolic parameters including blood glucose and lipid abnormalities.

Samidorphan, an opioid antagonist has been studied with Olanzapine and found to attenuate the effects of Olanzapine-associated changes in metabolic profile.

Treatment-emergent glycosuria has been reported in 6.1% of individuals taking Olanzapine vs 2.8% in those taking a placebo medicine [Ref]

Olanzapine is associated with dysregulated lipid metabolism. A rise in triglycerides of more than 50 mg/dl has been estimated to affect 39.6% of the patients taking Zyprexa vs 26.1% in the placebo group. Similarly, a rise in LDL and Total cholesterol may also occur in a significant number of patients taking Zyprexa.

The table below shows the percentage of patients who developed dyslipidemia with Zyprexa:

Change in Metabolic Parameters




Total Cholesterol >40 mg/dl1221.6%9.5%
LDL >30 mg/dl1223.7%14.1%
Triglycerides >50 mg/dl1239.6%26.1%

In one study, the effects of Lybalvi Vs Zyprexa on blood glucose and lipid parameters were studied in patients with schizophrenia.

The results of the study are summarized in the table below [Ref]:

Change in Metabolic Parameters



P Value

Fasting Insulin2417.30.3
Fasting Glucose-0.100.697
Total Cholesterol0.050.30.047

Although the difference was not very significant, larger studies are needed to evaluate the changes in metabolic parameters associated with Lybalvi and Zyprexa.



Lybalvi Vs Zyprexa (Olanzapine): Side Effects Reviews

Common side effects associated with Lybalvi are listed in the table below. Both drugs can cause somnolence, weakness, and Parkinson-like effects immediately after starting the treatment.

Here is a table comparing the side effects of Olanzapine Vs Lybalvi [Ref]:

Side effects




Orthostatic hypotension1 (5.0)8 (23.5)8 (22.9)
Somnolence1 (5.0)8 (23.5)7 (20.0)
Liver function test abnormal07 (20.6)5 (14.3)
Postural orthostatic tachycardia syndrome1 (5.0)4 (11.8)7 (20.0)
Nausea5 (25.0)3 (8.8)2 (5.7)
Blood creatine phosphokinase increased1 (5.0)3 (8.8)6 (17.1)
Headache4 (20.0)3 (8.8)1 (2.9)
Blood pressure decreased04 (11.8)5 (14.3)
Sedation1 (5.0)5 (14.7)2 (5.7)
Dizziness03 (8.8)5 (14.3)
Dry mouth1 (5.0)5 (14.7)1 (2.9)
Increased appetite02 (5.9)5 (14.3)

In addition, Lybalvi is contraindicated in patients who are taking opioid drugs or planning to taper off opioids

Lybalvi Vs Zyprexa (Olanzapine): Cost Comparison

Lybalvi is a newly-approved drug and hence low-cost generic alternative drugs are not available. Zyprexa is available worldwide with different generic brands which are much cheaper than Zyprexa.

The monthly cost of Lybalvi is estimated at $1600 USD while that of Zyprexa is $348 USD.

In addition, Zyprexa is available in different formulations such as Oral tablets, Oral disintegrating tablets, and Intramuscular injections. Lybalvi is only available as oral tablets.



In Conclusion:

Lybalvi is a fixed-dose combination of Samidorphan and Olanzapine (Zyprexa). It has the same indications as Zyprexa, however, it is less likely than Zyprexa to cause weight gain, hyperglycemia, and dyslipidemia.

It is only available as Lybalvi and is almost 5 times costlier than Zyprexa.

What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

I love my family, my profession, my blog, nature, hiking, and simple life. Read more about me, my family, and my qualifications

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