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Saphris (asenapine) is a prescription medication that belongs to the class of drugs called atypical antipsychotics. It is used to treat schizophrenia and bipolar disorder in adults and children. In this article, we will review what Saphris is, its history, how it works, the evidence for its use, its side effects, and its pros and cons.

What is Saphris (Asenapine)?

Saphris is the brand name of asenapine, a chemical compound that was derived from modifying the structure of mianserin, an antidepressant. ² Saphris comes in the form of sublingual tablets that dissolve under the tongue. It is available in two strengths: 5 mg and 10 mg. ¹ Saphris is also sold under the name Sycrest in Europe and Secuado in the US as a transdermal patch. ²

History

Saphris was developed by Schering-Plough, a pharmaceutical company that merged with Merck & Co. in 2009. ² Saphris was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of schizophrenia and bipolar mania in adults.  In 2013, it was approved for the treatment of bipolar mania in children aged 10 to 17 years. ¹ In 2015, it was approved by the European Medicines Agency (EMA) for the treatment of acute mania in bipolar disorder in adults. ² In 2020, it became available as a generic medication in the US.

Mechanism of Action

Saphris works by affecting the activity of certain chemicals in the brain called neurotransmitters, such as dopamine and serotonin. These neurotransmitters are involved in regulating mood, thoughts, and behavior. Saphris blocks some of the receptors for these neurotransmitters, reducing their overactivity or underactivity. ¹²

Saphris has a unique pharmacological profile compared to other atypical antipsychotics. It has high affinity for serotonin 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7 receptors; dopamine D1, D2, D3, and D4 receptors; adrenergic alpha1 and alpha2 receptors; and histamine H1 receptors. It has moderate affinity for muscarinic M1 receptors. It has no affinity for benzodiazepine or opioid receptors. ¹²

The exact mechanism by which Saphris exerts its therapeutic effects is not fully understood. However, it is believed that its antagonism of serotonin 5-HT2A and dopamine D2 receptors contributes to its antipsychotic activity; its partial agonism of serotonin 5-HT1A receptors and antagonism of adrenergic alpha2 receptors may enhance its antidepressant and cognitive effects; its antagonism of histamine H1 receptors may cause sedation; and its antagonism of muscarinic M1 receptors may cause anticholinergic side effects. ¹²

Evidence for use

Saphris has been studied in several clinical trials for its efficacy and safety in treating schizophrenia and bipolar disorder.

Schizophrenia

Saphris has been shown to be effective in reducing the positive and negative symptoms of schizophrenia in adults compared to placebo or other antipsychotics such as olanzapine, risperidone, or haloperidol.    Saphris has also been shown to improve cognitive function and quality of life in patients with schizophrenia.  

Saphris has been shown to be effective in treating schizophrenia in children aged 10 to 17 years compared to placebo.  However, Saphris is not approved for schizophrenia in children younger than 18 years old in the US or Europe.

Bipolar disorder

Saphris has been shown to be effective in treating acute manic or mixed episodes associated with bipolar I disorder in adults compared to placebo or other mood stabilizers such as lithium or valproate.   Saphris has also been shown to prevent relapse of manic or mixed episodes in patients with bipolar I disorder who responded to acute treatment with Saphris.

Saphris has been shown to be effective in treating acute manic or mixed episodes associated with bipolar I disorder in children aged 10 to 17 years compared to placebo.

Saphris has not been studied for the treatment of bipolar depression or maintenance treatment of bipolar disorder as monotherapy in adults or children.

Side Effects/ Adverse reactions / Contradictions

Saphris can cause various side effects, some of which can be serious or life-threatening. The most common side effects of Saphris include:

- Drowsiness
- Dizziness
- Weight gain
- Increased appetite
- Dry mouth
- Nausea
- Constipation
- Headache
- Restlessness
- Anxiety
- Insomnia
- Tiredness
- Numbness or tingling in the mouth

Some of the serious side effects of Saphris include:

- Neuroleptic malignant syndrome (NMS): a rare but potentially fatal condition that causes high fever, muscle stiffness, confusion, fast or irregular heartbeat, and sweating. Seek emergency medical attention if you experience these symptoms.
- Tardive dyskinesia (TD): a movement disorder that causes involuntary movements of the face, tongue, lips, arms, or legs. This condition may be irreversible and may not improve after stopping the medication. Seek medical advice if you notice any abnormal movements.
- Metabolic changes: Saphris can cause high blood sugar, high cholesterol, and high triglycerides, which can increase the risk of diabetes, heart disease, and stroke. Monitor your blood sugar and lipid levels regularly and follow your doctor's advice on diet and exercise.
- Low blood pressure: Saphris can cause a sudden drop in blood pressure when you stand up, which can make you feel dizzy, faint, or fall. This is more likely to happen when you start taking the medication or when your dose is increased. To reduce this risk, get up slowly from a sitting or lying position and avoid alcohol and dehydration.
- Low white blood cell count: Saphris can lower your white blood cell count, which can make you more prone to infections. Seek medical attention if you have signs of infection such as fever, sore throat, cough, or flu-like symptoms.
- Increased prolactin levels: Saphris can increase the hormone prolactin in your blood, which can cause breast enlargement, breast discharge, missed menstrual periods, or decreased sexual ability in both men and women. Seek medical advice if you experience these symptoms.
- Seizures: Saphris can lower your seizure threshold and cause seizures in some people. This is more likely to happen if you have a history of seizures or other risk factors such as brain injury, alcohol withdrawal, or drug abuse. Seek emergency medical attention if you have a seizure while taking Saphris.
- Allergic reactions: Saphris can cause allergic reactions such as rash, hives, itching, swelling of the face, lips, tongue, or throat, difficulty breathing, or anaphylaxis. Seek emergency medical attention if you have any signs of an allergic reaction.

Saphris is not suitable for everyone and may interact with other medications or medical conditions. You should not take Saphris if you:

- Are allergic to asenapine or any of the ingredients in Saphris
- Have severe liver disease
- Are taking certain medications that can affect the heart rhythm 

Some of the pros or positives of Saphris (asenapine) are:

- It can be used for bipolar disorder in children aged 10 years and older. ³
- It comes in the form of sublingual tablets that dissolve under the tongue, which can be a good option for people who have difficulty swallowing tablets. ³
- It can be used alone or with lithium or valproate for bipolar disorder. ³
- It can reduce the positive and negative symptoms of schizophrenia and improve cognitive function and quality of life in adults. ²
- It can affect dopamine and serotonin activity in the brain, which can help regulate mood, thoughts, and behavior. ⁴

Some of the negatives or drawbacks of taking Saphris (asenapine) are:

- It can cause various side effects, some of which can be serious or life-threatening, such as neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, low blood pressure, low white blood cell count, increased prolactin levels, seizures, and allergic reactions. ¹²
- It can be expensive compared to other similar medications. ³
- It needs to be taken twice a day. ³
- It can't be used in people with severe liver problems. ³
- It has not been studied for the treatment of bipolar depression or maintenance treatment of bipolar disorder as monotherapy in adults or children. ²

Sources for negatives section:
(1) Saphris Side Effects: Common, Severe, Long Term - Drugs.com. https://www.drugs.com/sfx/saphris-side-effects.html.
(2) Asenapine (Sublingual Route) Side Effects - Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/asenapine-sublingual-route/side-effects/drg-20073429?p=1.
(3) Saphris (asenapine) - PsyCom. https://www.psycom.net/saphris-asenapine.
(4) Saphris (Asenapine Sublingual Tablets): Uses, Dosage, Side ... - RxList. https://www.rxlist.com/saphris-drug.htm.

Sources for positives section:
(1) Asenapine - Wikipedia. https://en.wikipedia.org/wiki/Asenapine.
(2) Saphris Reviews & Ratings - Drugs.com. https://www.drugs.com/comments/asenapine/saphris.html.
(3) Asenapine (Saphris) | NAMI: National Alliance on Mental Illness. https://nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Asenapine-%28Saphris%29.
(4) Asenapine (Saphris): Uses, Side Effects, Dosage & Reviews - GoodRx. https://www.goodrx.com/asenapine/what-is.

Sources for main article:
(1) Asenapine - Wikipedia. https://en.wikipedia.org/wiki/Asenapine.
(2) Saphris: Uses, Dosage & Side Effects - Drugs.com. https://www.drugs.com/saphris.html.