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Saphris Withdrawal Symptoms, Asenapine Side Effects, Treatment Help

Last Updated on September 19, 2022 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD

Antipsychotics, like Saphris, are generally prescribed at a time of debilitating crisis, with no time or focus available to consider how or when to undertake Saphris withdrawal.

After a crisis passes, one can ask whether moments of upset really necessitate a lifetime of being medicated? Of note, researchers are looking at whether antipsychotic medications actually reinforce psychosis by upregulating dopamine receptors, also called dopamine hypersensitivity, and this is a matter that must be carefully addressed and monitored in recovery.13

Do Your Symptoms
Require Saphris?

getting off saphris
Alternative to Meds has been the leading authority on guiding antipsychotic withdrawal and Saphris alternatives for over 15 years. We have published evidence regarding our success. Many factors may have been overlooked prior to a prescription of antipsychotics and certainly afterward. Alternative to Meds Center takes the time to sort out what happened, and what needs to be adjusted (nutrition/lifestyle/allergies/genetic factors/drug use, etc.) When we isolate the culprits, these can be addressed to resolve the underlying conditions. Then we find the medication may be reduced or even entirely eliminated and the client responds very well and continues to do so for the long-term in more than three-quarters of all cases we have treated.

Saphris (generic asenapine) is an atypical antipsychotic medication FDA approved for the treatment of schizophrenia and bipolar episodic mania. Saphris does cause weight gain but is noted for not causing as much excess weight gain compared to other antipsychotics.2,7,8

The medication is administered via a sublingual dissolving tablet twice a day. It is a chemical derivative of an earlier tricyclic antidepressant called mianserin. Before beginning or stopping a course of medication, researching the drug and its side effects, withdrawals and other topics is a recommended action. The information below may be helpful to an individual who is facing mental health challenges and gathering information to make the best choices regarding options for health care.

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What is Saphris (asenapine) Used For?

Saphris is prescribed in the treatment of adult schizophrenia, and for acute manic episodes of bipolar disorder in adults and pediatric patients from age 10 and up.2

Saphris (asenapine) Alternative Names and Slang

Asenapine is sold under various trade names, including Saphris© and Sycrest©. Asenapine is not known as a street drug, although it is not uncommon for prescription drugs to be diverted to the illicit market. Diversion of prescription drugs has become a thriving illicit market.9

Saphris (asenapine) Side Effects

Some side effects that can occur while taking Saphris may require medical attention. Some of the most concerning adverse effects may come on either suddenly or gradually over time. Speak to your prescribing physician immediately if any symptoms occur. Side effects may appear which are not on the below list and may signal medical attention is needed to investigate the matter further. Some symptoms are reported more commonly, which may be less severe, but should still be monitored as they may signal potential health problems. Somnolence is very commonly reported as a side effect of Saphris. Because of induced insulin resistance, weight gain is another frequently reported side effect of Saphris.1,2,16-18

Saphris side effects can include:
  • Akathisia — an adverse reaction caused by antipsychotic medications and other drugs. It manifests as an inability to sit still, an intense sense of unease, inner restlessness, and a compulsion to move.
  • Suicidal thoughts
  • Shakiness, tremors in the hands, limbs, etc.
  • Drooling
  • Difficulty or pain swallowing
  • Slowed heartbeat
  • Shuffling walk, unusual slowness in body motions
  • Dyskinesia, muscle spasms that cause the body to twist in unnatural postures, sometimes painful
  • Eye rolling
  • Facial grimacing
  • A fixed facial expression, mask-like facial characteristics
  • Intense anxiety
  • Feeling agitated
  • Irritability
  • Sudden weakness in the body
  • Rash with fever
  • Hives, weeping sores
  • Loss of unconsciousness
  • Skin sores
  • Mouth ulcers
  • Sores in the mucous tissues
  • Severe and sudden headache
  • Slurring words
  • Loss of balance
  • Blinking eye movements
  • Blurred vision
  • Tongue rolling, lip-smacking, chewing (involuntary)
  • Elevated levels of blood sugar
  • Fainting episodes (syncope)
  • Constipation
  • Dry mouth, altered taste sensors
  • Insomnia, interrupted or disturbed sleep
  • Nausea
  • Stomach pain
  • Increased appetite
  • Weight gain
  • Drowsiness
  • Vertigo, dizziness
  • Tingling feeling or numbness in body parts, i.e., mouth, hands, etc.
  • Feeling restless

Saphris (asenapine) Withdrawal Symptoms

Possibly the most concerning Saphris withdrawal symptoms would be a return of original symptoms, that may sometimes intensity, at least for a time. This is a characteristic of all antipsychotic medications. This may be a sign that the Saphris withdrawal is too fast, and should be eased up until a lessening of effect occurs. Attention should be given to potential dopamine hypersensitivity and other severe reactions that can occur during neuroleptic withdrawal.10-15

During Saphris withdrawal, other adverse effects should be watched for and may require medical intervention.

Saphris withdrawal symptoms can include:
  • Return of symptoms of psychoses, such as hearing voices, hallucinations, and altered perceptions.
  • Tremors
  • Intensified anxiety
  • Profuse sweating
  • Chills
  • Fever
  • Heart palpitations, tachycardia
  • Heavy feeling in the limbs, extremities hard to move
  • Mood swings, pronounced, may be rapid
  • Shuffling walk, rigidity, slowness in movements
  • Depersonalization
  • Deep depression
  • Jaw clenching
  • Flu-like symptoms
  • Insomnia, interrupted sleep patterns, vivid dreams
  • Fatigue
  • Somnolence

Discontinuing/Quitting Saphris (asenapine)

Saphris withdrawal is best done in a safe, inpatient setting so that proper monitoring can occur. Patient safety and comfort should be addressed, to ease the person through the process as comfortably as possible. Saphris withdrawal can be unpredictable and a very slow approach with supportive medical guidance is necessary.

Saphris (asenapine) FAQs

Below are some topics that are frequently researched on the drug, including how it works, interactions with other drugs, and other topics relating to Saphris withdrawal..

How does Saphris (asenapine) Work?

Saphris is dissolved under the tongue and is given twice per day in 5mg or 10mg tablets. The drug is not absorbed as well if swallowed.

How Saphris works is not yet completely understood. It is thought that the drug influences certain receptors in the brain. Asenapine could be referred to as a multi-receptor neuroleptic drug, which influences both serotonin and dopamine antagonism. The literature on the drug indicates that it can have beneficial effects on cognitive function and may reduce some unwanted symptoms in patients with schizophrenia. Researchers report an exceptionally high affinity for specific receptors that may be significant. However, the exact mechanics of how the drug works remain poorly understood.1,13

Comparisons from trials done showed Saphris to be only minimally effective for acute mania compared to most other antipsychotic medications.2

It is believed that antipsychotics such as Saphris deflect dopamine from binding at the D2 receptor. This is thought to correlate to the drug’s ability to reduce psychotic symptoms. However, there is a limitation to any drug’s effectiveness over time because the body adapts by building new receptors.

This adaptation can make trying to withdraw from antipsychotic medication extremely difficult, sometimes described as more challenging than benzodiazepine or heroin withdrawal.

This difficulty may be caused, at least in part, by another aspect of antipsychotic medication. Withdrawal can become hard to manage because when the drug is reduced, a significant flood of dopamine may occur as a result of dopamine hypersensitivity. This can clinically present as a return of manic symptoms.

The patient may become, affected by this reaction, unwilling or unable to follow directions. It may be desirable at such a point to arrange hospital admission for stabilization. Once stabilized, tapering may be able to resume at a slow pace. This scenario would not occur in all cases, but the possibility may be more likely where medication has been relied on for many years. Such considerations should be discussed prior to beginning tapering. With exacting, well-planned, and compassionate protocols, it is possible in most cases to transition to medication free, or to the lowest possible dose that still provides satisfactory quality of life.

As a general note, it is usual that a drug such as Saphris is given during a time of crisis or to control an extreme type of episode. Less attention is often given to determining whether such a crisis was a temporary situation. It may be easier to find a doctor to prescribe Saphris or similar medication than it is to find a doctor familiar enough with correct tapering to help with the reduction or elimination of the drug when that time comes. Inpatient help may be able to answer this problem, where the staff is familiar with and capable of helping with Saphris withdrawal.

What Does Saphris Do To The Brain?

After collating information based on a number of clinical studies, we have seen what appears to be a correlation between the COMT genetic polymorphism and mania, psychosis, as well as depression related to bipolar conditions.

One theory is that dopamine, being the reward chemical, and other neurochemicals with their respective functions, may be affected by changing rates of efficacy due to certain genetic impairment factors present that interfere or interact with various catecholamines along the neuronal pathways.

For instance, if the breakdown of dopamine is a result of COMT impairment, as indicated by the presence of the COMT genetic polymorphism, it would be reasonable to assume the person may be experiencing an excess of dopamine. Saphris is associated with tardive dyskinesia and other movement disorders, and concern has been reported in medical reports on these adverse reactions. 

Studying the role of genetics may prove increasingly important as more research is done along these lines.

Can You Drink on Saphris (Asenapine)?

Since the drug is dissolved in the mouth, eating or drinking anything should be avoided for ten minutes after taking a Saphris pill.

Drinking alcohol at any time during treatment with Saphris may cause dangerous interactions and so should be avoided at all times. Drugs and alcohol can have unpredictable consequences and may lengthen your time in treatment, as well as pose certain health risks that may lead to hospitalization, and may extend recovery time considerably.

Healthy Alternatives for Hobbies, Social Interactions, Personal Enhancement

A better approach to attaining mental health naturally might include finding other things besides alcohol that satisfy the need for enjoyment and relaxation. After all, life, though challenging at times, is meant to be enjoyed. That enjoyment may be enhanced further by finding healthier alternatives such as hobbies, social outings, nature hikes, massage therapy, spa treatments, etc., that may provide additional opportunities for improvement.

As a side note of caution, while taking Saphris or any drug that causes drowsiness, do not drive a vehicle or operate heavy machinery as you may not be alert enough to do so safely. Staying safe, and helping others stay safe doesn’t mean that life can’t be enjoyed. In fact, there is great therapeutic value in finding new and challenging activities that stimulate creative thought and new abilities.

This may be especially pertinent to someone suffering from schizophrenia or other mental disorders. Disordered thinking can create stress and difficulties almost beyond imagining, however, finding alternatives to drinking alcohol will provide many opportunities for improvements that may not have otherwise been discovered.

How Long Does Saphris Stay in Your System?

how long does saphris stay in your systemSaphris has an approximate elimination half-life of 24 hours.

There is limited published data as to how long Saphris will show positively on drug testing beyond testing on postmortem specimens.4

Per the Psychopharmacology Institute,

“Asenapine is a high clearance drug with a clearance after intravenous administration of 52 L/h. In this circumstance, hepatic clearance is influenced primarily by changes in liver blood flow rather than by changes in the intrinsic clearance, i.e., the metabolizing enzymatic activity. Following an initial more rapid distribution phase, the terminal half life of asenapine is approximately 24 hours.” 5

However, a more pertinent question might be how long will a person feel the effects after stopping Saphris? Because of the body’s neuroadaptive ability, adequate time should be allowed for the body and neurochemistry to normalize. The gentle taper approach will mitigate after-effects considerably, and other factors can help to accelerate recoveries, such as diet, sleep habits, and other pragmatic types of recovery support.

Treatment for Saphris (asenapine) Abuse and Addiction?

Alternative to Meds Center provides a serene and comfortable inpatient setting in which to recover after a course of prescription medication such as asenapine needs to be tapered.

With carefully tailored individual programming, the specific needs of each client can be addressed safely and with a minimum of discomfort.

With a well-trained staff of over forty professionals, doctors, nurses, practitioners, and counselors, the center takes a thorough and comprehensive approach to health recovery after medication.

An important facet of the program entails testing for and removing toxic accumulations of various environmental pollutants, chemicals, and other substances that are neurotoxic. The program seeks to normalize neurochemistry through holistic means such as flooding the body with nutrient-rich foods, proper supplementation, and many other methods. When this phase of the program is complete, clients will typically see improvements in sleep, energy level, mood, less depression, less anxiety, and other positive results. Beginning a taper when the improvements have already bet set in motion is much easier on the system and much more comfortable done in this way.

getting off saphrisMany adjunct therapies are used in the programs as well, so that maximum client support is made available. Some of these include mind/body techniques like Qigong, yoga, counseling specific to disordered thinking, educational classes on designing and maintaining a healthy diet, high-dose vitamin C therapy, as well as other orthomolecular applications specific to this population.

Families are often troubled by the stress of watching a loved one suffer. It can be much easier for the people who surround the person needing help to consider inpatient treatment. Please contact us for more information on our cutting-edge programs. Learn how knowledge can assist you as you begin your quest toward natural mental health. Find out about how gentle Saphris withdrawal can be, done in the comfort and support of an environment filled with professionals who understand how to fulfill the full scope of a client’s needs and issues.

1 (800) 301-3753 for Saphris Withdrawal Help

1. Schering-Plough Saphris (Asenapine) drug pharmacology [INTERNET] Centerwatch.com 2009 Aug 18

2. FDA Saphris (asenapine) label information, approval 2009, [cited 2022 Sept 14]

3. Diamond A. Consequences of variations in genes that affect dopamine in prefrontal cortex. Cereb Cortex. 2007 Sep;17 Suppl 1(Suppl 1):i161-70. doi: 10.1093/cercor/bhm082. PMID: 17725999; PMCID: PMC2238775. [cited 2022 Sept 14]

4. Miller C, Pleitez O, Anderson D, Mertens-Masham D, Wade N Asenapine (Saphris®): GC–MS Method Validation and the Postmortem Distribution of a New Atypical Antipsychotic Medication Journal of Analytical Toxicology [INTERNET] 2013 Oct 01

5. Guzman F MD Asenapine (SAPHRIS) Pharmacokinetics open-access article Psychopharmacology Institute [published onlinee 11/01/2015] last updated 2019 Jun 27 [cited 2022 Sept 14]

6. Plosker GL, Deeks ED. Asenapine: A Review in Schizophrenia. CNS Drugs. 2016 Jul;30(7):655-66. doi: 10.1007/s40263-016-0363-2. PMID: 27356921. [cited 2022 Sept 14]

7. Citrome L. Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract. 2009 Dec;63(12):1762-84. doi: 10.1111/j.1742-1241.2009.02228.x. Epub 2009 Oct 14. PMID: 19840150. [cited 2022 Sept 14]

8. McIntyre RS, Wong R. Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia. Clin Schizophr Relat Psychoses. 2012 Jan;5(4):217-20. doi: 10.3371/CSRP.5.4.6. PMID: 22182459. [cited 2022 Sept 14]

9. Inciardi JA, Surratt HL, Kurtz SP, Cicero TJ. Mechanisms of prescription drug diversion among drug-involved club- and street-based populations. Pain Med. 2007 Mar;8(2):171-83. doi: 10.1111/j.1526-4637.2006.00255.x. PMID: 17305688; PMCID: PMC2879025. [cited 2022 Sept 14]

10. Patel J, Marwaha R. Akathisia. [Updated 2022 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519543/ [cited 2022 Sept 14]

11. Dilsaver SC, Alessi NE. Antipsychotic withdrawal symptoms: phenomenology and pathophysiology. Acta Psychiatr Scand. 1988 Mar;77(3):241-6. doi: 10.1111/j.1600-0447.1988.tb05116.x. PMID: 2899377. [cited 2022 Sept 14]

12. Amore M, Zazzeri N. Neuroleptic malignant syndrome after neuroleptic discontinuation. Prog Neuropsychopharmacol Biol Psychiatry. 1995 Dec;19(8):1323-34. doi: 10.1016/0278-5846(95)00269-3. PMID: 8868212. [cited 2022 Sept 14]

13. Horowitz MA, Jauhar S, Natesan S, Murray RM, Taylor D. A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse. Schizophr Bull. 2021 Jul 8;47(4):1116-1129. doi: 10.1093/schbul/sbab017. Erratum in: Schizophr Bull. 2022 Jun 21;: PMID: 33754644; PMCID: PMC8266572. [cited 2022 Sept 14]

14. Glazer WM, Morgenstern H, Schooler N, Berkman CS, Moore DC. Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication. Br J Psychiatry. 1990 Oct;157:585-92. doi: 10.1192/bjp.157.4.585. PMID: 1983390. [cited 2022 Sept 14]

15. Asenapine: a less effective, yet, more dangerous neuroleptic! Prescrire Int. 2012 Oct;21(131):229-32. PMID: 23185842. [cited 2022 Sept 14]

16. Gonzalez JM, Thompson PM, Moore TA. Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder. Patient Prefer Adherence. 2011;5:333-41. doi: 10.2147/PPA.S10968. Epub 2011 Jul 1. PMID: 21792304; PMCID: PMC3140314. [cited 2022 Sept 14]

17. Citrome L. Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics. Postgrad Med. 2011 Mar;123(2):153-62. doi: 10.3810/pgm.2011.03.2273. PMID: 21474903. [cited 2022 Sept 14]

18. Tarazi FI, Stahl SM. Iloperidone, asenapine and lurasidone: a primer on their current status. Expert Opin Pharmacother. 2012 Sep;13(13):1911-22. doi: 10.1517/14656566.2012.712114. Epub 2012 Jul 31. PMID: 22849428. [cited 2022 Sept 14]

Originally Published Sep 13, 2018 by Diane Ridaeus


This content has been reviewed and approved by a licensed physician.

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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