Asenapine (Saphris, Secuado)

What it treats

Asenapine sublingual (Saphris) is FDA-approved for schizophrenia in adults, acute manic or mixed episodes of bipolar I in adults and children age 10 and older, and maintenance treatment of bipolar I. Asenapine transdermal (Secuado) is approved for schizophrenia in adults. The patch is useful for people who can't tolerate the oral hypoesthesia or who struggle with the "don't eat or drink for 10 minutes" rule that comes with the sublingual tablet.

How it works

Asenapine is an atypical antipsychotic that acts on several receptors at once. It blocks dopamine and serotonin receptors, which reduces hallucinations, delusions, and manic symptoms, and it also has effects on histamine and adrenergic receptors that shape its side-effect profile.

Receptor mechanism (detail)

Asenapine is a broad-spectrum antagonist at dopamine D2, serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7, along with alpha-1 and alpha-2 adrenergic and histamine H1 receptors. That wide receptor profile is associated with its clinical effect in schizophrenia and mania. Muscarinic activity is low, which is why anticholinergic side effects are minimal.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

For sublingual Saphris, a typical dose is 5 to 10 mg twice daily. The tablet dissolves under the tongue over about a minute, and nothing should be eaten or drunk for 10 minutes afterward to allow absorption. For transdermal Secuado, the dose is 3.8, 5.7, or 7.6 mg per 24 hours, applied as a patch once daily. The prescriber sets and adjusts the dose based on response and side effects.

Safety monitoring

• Weight, BMI, fasting glucose or HbA1c, and lipids at baseline, week 12, and at least annually. Asenapine's metabolic effects are moderate, less than olanzapine but more than lurasidone or aripiprazole.
• Blood pressure at baseline and periodically.
• Involuntary-movement screen (AIMS) every six months.
• Movement side-effect check at each early visit.
• Oral exam for sublingual users, some develop oral ulcers.
• Skin check for patch users, some develop application-site irritation.

Metformin co-commencement: Aoife Carolan / Schizophrenia Bulletin guideline.

A clinical guideline led by Aoife Carolan strongly recommends co-commencing metformin alongside high-risk antipsychotics like olanzapine or clozapine. This proactive approach helps mitigate severe metabolic side effects, significantly reducing antipsychotic-induced weight gain and improving insulin resistance. The Schizophrenia Bulletin guideline states that when prescribing olanzapine or clozapine, metformin should be initiated immediately to prevent weight gain and cardiometabolic issues. Asenapine has moderate metabolic risk and isn't on the automatic co-commencement list, but metformin is recommended if weight rises more than 3 percent of pre-medication weight or if other cardiometabolic risk factors are present.

Typical titration used in the guideline: 500 mg once daily, then 500 mg twice daily after one week, then 500 mg increments every two weeks as tolerated, up to 1000 mg twice daily by about week six. Contraindicated with eGFR below 30 mL/min/1.73 m². Renal function is checked annually and metformin is held during acute illness or dehydration.

Source: Carolan A, et al. Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophrenia Bulletin. 2025;51(5):1193 to 1203.

What to expect

Common side effects

• Oral hypoesthesia (numbness) with the sublingual form, in the first few minutes after a dose.
• Sedation.
• Dizziness, especially on standing.
• Weight gain, modest to moderate.
• Akathisia.
• Nausea.
• Skin irritation at the patch site (Secuado).

Serious side effects and warnings

Boxed warning. Asenapine carries the FDA boxed warning that antipsychotics increase the risk of death in older adults with dementia-related psychosis, and it isn't approved for that use.

• Severe allergic reactions. Serious hypersensitivity, including anaphylaxis and angioedema, has been reported with sublingual asenapine. Any swelling of the tongue, throat, or face after a dose is a medical emergency.
• Neuroleptic malignant syndrome. Rare but serious.
• Tardive dyskinesia. Long-term antipsychotic use can produce involuntary movements. Risk rises with dose and duration.
• Metabolic changes, weight gain, elevated glucose, elevated lipids.
• QTc prolongation, mild to moderate.
• Orthostatic hypotension.

This isn't medical advice. Any concern about a serious side effect should be raised with a prescriber promptly.

Sexual side effects

Asenapine can lower sex drive or cause erectile problems. Its effect on prolactin is generally mild. If sexual side effects appear, it's worth raising with the prescriber.

Weight, appetite, and sleep

Weight gain with asenapine is typically modest to moderate, less than with olanzapine or clozapine. Sedation often helps sleep, especially with evening dosing.

Starting and dosing basics

This section is general background, not a dosing instruction. Saphris comes as sublingual tablets. Place the tablet under the tongue and let it dissolve, don't chew or swallow it, and don't eat or drink for 10 minutes afterward. Secuado comes as a once-daily patch, applied to the hip, abdomen, upper arm, or upper back, rotating sites.

Missed doses and interactions

For the sublingual form, if you miss a dose, take it when you remember unless it's almost time for the next one, then skip and carry on. For the patch, apply the next patch when you remember and stay on the same daily schedule.

Asenapine interacts with alpha-blockers, other sedating drugs, and drugs that prolong QTc. The prescriber and pharmacist need a full list of medications and supplements. Alcohol worsens sedation.

Stopping and tapering

Don't stop asenapine abruptly. A prescriber can step the dose down gradually.

Pregnancy and breastfeeding

Untreated psychosis and untreated mania both carry their own risks in pregnancy, and asenapine passes into breast milk. Anyone who's pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber. This isn't medical advice.

Cost and generic availability

Generic asenapine sublingual is available. Secuado remains brand-only and is considerably more expensive. Insurance coverage varies. Manufacturer patient assistance programs exist for Secuado.

Common questions

Why does the tablet go under the tongue? Asenapine has very poor absorption when swallowed, less than 2 percent reaches the bloodstream. Sublingual absorption bypasses that problem. The 10-minute food and drink rule protects that absorption.

What is oral hypoesthesia? A numb feeling in the mouth and tongue for a few minutes after a sublingual dose. It's usually mild and fades quickly. It doesn't mean something's wrong.

Why choose the patch over the tablet? The patch avoids the oral numbness and the food and drink rule, which suits some people better. It's also useful for people who forget mid-day doses or find twice-daily dosing hard.

How does asenapine compare metabolically with olanzapine? Weight gain and metabolic changes are meaningful but generally less than with olanzapine. Baseline and follow-up monitoring still matter.

Is asenapine ever used for treatment-resistant depression or anxiety? Not typically. Its FDA indications are schizophrenia and bipolar I. Off-label use for other conditions is uncommon.

Questions to ask your prescriber

• What are we hoping this treats, and how will we know it's working?
• Would the sublingual or the patch fit my life better?
• What should I do if I feel numbness or swelling in my mouth?
• How closely will we track weight and labs?
• If we decide to stop it later, how would we taper safely?

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes, and current as of June 8, 2026.

• U.S. Food and Drug Administration. Asenapine (Saphris, Secuado) prescribing information.
• MedlinePlus, U.S. National Library of Medicine. Asenapine.
• National Institute of Mental Health. Mental health medications.
• American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia, 3rd edition.
• National Institute for Health and Care Excellence (NICE). CG178, Psychosis and schizophrenia in adults.
• Carolan A, et al. Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophrenia Bulletin. 2025;51(5):1193 to 1203.