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Invega Withdrawal Symptoms, Paliperidone Side Effects, Treatment Help

This entry was posted in Antipsychotic on by .
Medically Reviewed Fact Checked

Last Updated on July 23, 2021 by Carol Gillette

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

Prescribers generally have minimal exposure to Invega withdrawal — it just isn’t their scope. Invega is an antipsychotic that is utilized during a time of crisis. Long-term ramifications and side effects of Invega shouldn’t be discounted.

Unskilled withdrawal from Invega, after the dopamine receptors have upregulated, can put a person right back into crisis. The supervision must be handled with extreme care.

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What Is Invega?

Invega, generic paliperidone, is an oral extended-release tablet or injectable antipsychotic medication used in the treatment of schizophrenia in adolescents and adults.1

Neither the monthly injectable form, Invega Sustenna©, or the 3-month injectable Trinza©, or the oral daily form is approved for elderly patients with dementia-related psychosis due to increased risk of death, according to the FDA black box warning for the drug. When possible, it is always advisable before beginning treatment with a potent medication, to research the side effects, possible withdrawal symptoms, and other health-related information as thoroughly as you can. In a crisis situation, this is often not possible. But after such a crisis has passed, and before attempting to withdraw from such medication, it may become clear that the benefits are outweighed by the risks of continuing such medication. In that case, the medication should be at least reduced or stopped, or other alternatives should be employed, according to research published by the Official World Psychiatry Journal.20 We provide information for personal research and discussions with your prescriber about how to approach Invega withdrawal. Medication withdrawal must be uniquely programmed for any individual, and methods such as cross-tapering, or transitioning from an injectable to a capsule or tablet version, or other interventions may be possible.

Invega (paliperidone) Withdrawal Symptoms

invega withdrawal symptomsIt is recommended to start taking Invega at the lowest possible dose and to take as low a dose as possible during treatment. This is because Invega withdrawal may be easier if the maintenance dose is kept as low as needed to control symptoms. Once a person has stabilized, which can mean eating and sleeping regularly, and not experiencing uncontrolled rage, debilitating hallucinations, mania, or psychosis, Invega withdrawal can become an option to consider. In a review published in the Journal of Psychiatry Research, over 100 patients who attempted antipsychotic medication withdrawal were surveyed. It was found that the gradual approach to coming off the drugs was associated with much fewer adverse withdrawal symptoms, as well as fewer relapses in the majority of participants responding to the survey.10

An extensive review of the medical literature on antipsychotic withdrawals was analyzed by Brandt et al in their study published in Sept 2020 in the Frontiers in Psychiatry Journal. The authors reported that fast or abrupt antipsychotic withdrawal by far produces more intense withdrawals, and that slow reductions produce less severe reactions as a general rule. Of note, women and older populations suffered greater intensity of withdrawal phenomena in some of the trials analyzed. The list of withdrawal symptoms below is drawn from this study,14, and several other sources as indicated, though this may not be a complete list.

Invega Withdrawal Symptoms Include:

  • Nausea, vomiting, abdominal pain, diarrhea, dizziness, tremors, shakiness.9
  • Headache, myalgia, numbness, vertigo, diaphoresis, restlessness, tension, insomnia, nightmares, hyperkinesia, dry mucous membranes, tachycardia, anxiety, bad taste, rhinorrhea (runny nose) 14
  • Akathisia 13
  • Depression, mania, psychosis, hallucinations, or other returning or rebound symptoms which can be more severe than before starting medication.15,16

*Akathisia is receiving attention and new research since it is a common side effect of withdrawal from several types of psychiatric medications, including antipsychotics.13

Discontinuing/Quitting Invega

Invega withdrawal should be done in close and regular coordination with the prescribing physician who can adjust the dose at intervals to soften the withdrawals that may present.

Quitting Invega suddenly is not recommended except if medically necessary. For example, if tardive dyskinesia emerges, the condition can become permanent but has reversed in some cases when the drug was immediately withdrawn. Another adverse reaction is named neuroleptic malignant syndrome.12 NMS has been reported with Invega and other antipsychotic medications, and the severity of symptoms can quickly become life-threatening. The appropriate medical response is to immediately discontinue Invega and seek emergency hospital care.1,11-13

At times, it may be deemed necessary to switch one antipsychotic (one that is not working) to another, with no gradual reduction attempted–but this would only be done in a clinical setting, under cautious, careful observation.14

We must stress that outside of these medical emergencies, Invega withdrawal should be done very very slowly, with careful and attentive medical monitoring in place. An inpatient setting such as Alternative to Meds Center is our best recommendation for stabilized candidates who seek treatment for Invega withdrawal as we have over 40 clinical, medical, and support staff ready to assist our clients 24/7.

Dopamine and Coming Off Antipsychotic Medications

dopamine and antipsychotic medsIn looking at reasons why Invega withdrawal needs such careful monitoring and management, perhaps the most troubling one is what is called antipsychotic-induced dopamine supersensitivity psychosis.6,7 Despite the complex-sounding name, a rough analogy for this phenomenon might be how firefighters manage the terrific force of a working firehose. When the valve is opened, it takes at least 2 firefighters shoulder-to-shoulder to control the explosive force of the water. A similar thing happens when you reduce antipsychotic medications (that dampen dopamine expression) too quickly. Reducing the medication releases the “clampdown” effect which prompts a sudden upsurge of dopamine. This is best managed by very, very, slow reduction rates, with ample time to settle out between incremental dosage cuts. When the drug is reduced, dopamine expression returns and if this happens too quickly, returning manic symptoms may result.

In some extreme cases, the patient may become resistant to being guided or following directions in treatment, due to the enchantment of this sensation of an enhanced sense of reward. Such unwillingness to take pragmatic guidance can make the situation hard to manage well. Working with a physician who has hospital admitting privileges would be advised to regain control in a compassionate way, as stabilization may become necessary, for such extreme cases, in a hospital setting. Where the taper was too rapid or otherwise unstructured, this can be especially relevant to bear in mind.

Sometimes a “Ulysses contract” may be advised, where a signed agreement is made between the person wanting to reduce their antipsychotic medication and a trusted friend or caregiver involved or guiding them through treatment. In the voluntary agreement, it is stipulated that if the person suddenly decides to just stop the medication suddenly, or take an unplanned vacation from supervised treatment, that they understand that the police or hospitalization may have to become involved.9

What Invega Is Used For

Invega (paliperidone) and Invega Sustenna are FDA approved to be used in the treatment of schizophrenia in adolescents and adults. (see cautions below) Other uses include as an adjunct medication to antidepressants and mood stabilizers. These approvals were granted after a small number of very short clinical trials lasting 6 weeks.1

CAUTIONS

1. There is a warning on the FDA label that indicates the drug causes increased mortality in elderly patients with dementia-related symptoms of psychosis.

2. Use in the third trimester of pregnancy and while breastfeeding is associated with neonatal withdrawals and movement disorders in the infant. Human trials have not established safety with regard to birth defects.

3. Safety has not been established for the treatment of persons below the age of 18 for schizoaffective disorders or in patients age 12 or younger in the treatment of schizophrenia.

4. Long-term treatment with antipsychotic medications may see decreasing efficacy, along with some undesirable health consequences, as reported in the Official World Journal of Psychiatry in 2018.17

Invega Alternative Names and Slang

Invega (paliperidone) refers to the oral pill form taken once every morning. The injectable forms, Invega Sustenna, and Invega Trinza are administered by intramuscular injection monthly or every 3 months respectively. No street popularity or slang names for this drug can be found in a broad search of medical literature.

Invega Side Effects 19

The injectable form of Invega commonly causes reactions at the injection site. Antipsychotic medications are associated with extrapyramidal disorders, defined as:

  • Acute dyskinesia
  • Dystoric reactions
  • Tardive dyskinesia
  • Parkinsonism
  • Akinesia
  • Akathisia
  • Neuroleptic Malignant Syndrome (NMS)
  • Hyperprolactinemia

Invega can cause these common side effects:

  • Tremors/shakiness
  • Swelling in breast tissue (males and females), discharge from breasts
  • Irregular menstrual periods
  • Restlessness
  • Nausea and vomiting
  • Lowered cognitive function
  • Drowsiness
  • Stomach pain, abdominal cramping
  • Headache
  • Dizziness, lightheadedness
  • Weight gain, constipation
  • Dry mouth
  • Cough
  • Decreased libido, anorgasmia, impotence
  • Blurred vision

Severe Invega side effects though rare may require medical attention:

  • Drug-induced catatonia, muscle rigidity, akathisia, memory lapse, tachycardia, unresponsive though awake 18,19
  • Tardive dyskinesia, uncontrolled motor movements, i.e., smacking lips, rolling tongue, twisting or frowning the face, jerking hands, limbs
  • NMS
  • Myocarditis
  • Agranulocytosis, susceptibility to infection
  • Mood swings, i.e., anger to uncontrolled crying spells
  • Sudden high fever, sore throat, or other signs of infection or low white blood count
  • Profuse sweating
  • Impaired cognitive function, confusion
  • Feeling like fainting, sudden weakness
  • Sudden numbness, especially if on one side only
  • Severe or sudden headache
  • Sudden problems with vision
  •  Arrhythmia
  • Difficulty speaking
  • Loss of balance or coordination
  • Flu-like symptoms, i.e., chills, aches, etc.)
  • White patches or ulcers on the inside of the mouth or lips

Since a patient on Invega may have limited ability to articulate what may be happening, careful and continuous monitoring of the person by observers is extremely important.

Stabilization During Invega Tapering

Once the patient is stabilized, slow tapering is possible so the patient may be able to transition to becoming medication-free, or to the lowest possible dose that still provides satisfactory quality of life.

It may be easier to find a physician to begin a patient on Invega than to find one who is familiar with helping a patient to come off the drug. When seeking clinical or medical help for tapering, choose a physician with familiarity and confidence in their ability to help.


Invega FAQs

Below are some common questions asked about Invega, and some other topics that may be helpful in considering stopping or starting Invega.

What Does Paliperidone Do to the Brain?

It has not been entirely established what antipsychotic medications do to the brain. It is thought that Invega acts primarily on the activity of dopamine and possibly other receptors in the brain. Of historic note, this idea was first proposed after Swiss chemist Albert Hoffman’s own reactions to taking LSD back in the 40s 22 where he developed this theory about imbalances of serotonin, dopamine, glutamate, and other molecules in the brain. Invega and other antipsychotics are thought to reduce the excess activity of dopamine. The idea really caught fire in the 80s when the manufacturing of atypical antipsychotic drugs really took off. Thus, Invega is thought able to help control the symptoms of psychosis and schizophrenia by dampening the expression of dopamine. There may be other molecules and other areas of interest that need studying to really be able to treat mental illness, in its broader context as a complex aspect of human health.

In clinical studies, we have seen a correlation between COMT impairment and features of psychosis, mania, and high and low moods that are attributed to bipolar disorder, drug-induced mania, and other disorders.21,23 COMT stands for catecholamine methyltransferase, where catecholamines include norepinephrine, adrenaline, and dopamine. Methyltransferase refers to certain genetic factors relating to the metabolizing of catecholamines, i.e., determining how efficient or how impaired the metabolization process may be. More research is ongoing on these and related areas.

Notes on Schizophrenia and Excitatory Neurotransmitters

Excitatory neurotransmitters such as dopamine produce excitatory effects on the brain, affecting emotions, and other responses, including the dopaminergic effect on the perception of reward. A person with a low sense of reward might be more inclined toward using stimulants, and conversely, the individual who is experiencing an elevated sense of reward may present mania-type symptoms.

More research is needed to understand more about schizophrenia and other disorders and the effects on neurotransmitters, that medications cause in the brain and CNS.

How Long Does Invega (Paliperidone) Stay in Your System?

We can approximate the half-life of Invega in tablet form to be roughly 24 hours. Half the drug would be cleared in that period. When the drug is taken by injection it would be much longer, calculated anywhere from 24 to 49 days for half of the drug to be eliminated from the body. 25,26

Because of the neuroadaptive effects of the drug, the effects of Invega may last much longer. Other factors that would contribute to answering the question of how long drug effects persist might include diet, duration of drug use, genetics, etc. It would be very difficult to predict but could be reasonably estimated as months or even years.

However, safe Invega withdrawal, along with the use of neurotransmitter precursors has been demonstrated to diminish these time projections considerably.

Is Invega Used for Depression?

Invega is approved by the FDA for treating schizophrenia. However, other off-label uses have developed such as prescribing the drug to treat the symptoms of depression, bipolar disorders, or mixed episodes of depression.2

When the drug is prescribed for off-label uses, this practice does not preclude the importance of avoiding alcohol, opiates, or any other substances that could worsen Invega side effects.

Is Invega the Same as Risperdal?

Invega is a derivative produced from an active metabolite of Risperdal (risperidone). Though their effects are similar, they are different in molecular structure.24

Both Risperdal and Invega are used in the treatment of schizophrenia.

Best Treatment for Invega Withdrawal

Alternative to Meds Center helps patients to make improvements to their mental and emotional health without focusing on medicating or labeling the patient as having some permanently broken diagnosis.

While medication can play a necessary role in reducing symptoms, the authoritative textbook The Clinical Handbook of Schizophrenia states that “medications alone are inadequate to manage schizophrenia.” 3

There are many additional treatment options such as CBT and other forms of psychological counseling that can be recommended as part of an effective Invega withdrawal treatment plan. Holistic treatment options designed to support mental health naturally are described in more detail on Alternative to Med’s services overview page. Some candidates may be able to reduce medication and some may be able to discontinue Invega altogether. The individualized plan for each client addresses these unique needs and circumstances.

Attaining Mental Health Naturally

In some cases, Invega withdrawal may be a safe way to attain mental health naturally, supporting the transition with alternative treatments. Each of our clients has a unique personal history that must be consulted through every step of the treatment plan that is designed for the person.

invega addiction holistic treatmentsOne of the most important features of our Invega withdrawal program is the removal of neurotoxins from the body. This toxic load might comprise many neurotoxic chemicals and substances, heavy metals, accumulated pesticides, drug residues, etc., which when eliminated can bring about many benefits. Testing will show the presence of these and other toxic accumulations, and also confirm their reduction or absence after cleansing.4,5

Once the cleanse step is complete, typically clients report sleeping better, feeling calmer, brighter, with improved appetite and other good changes. While in the program, clients use pharmaceutical-grade supplements, vitamins, minerals, nebulized glutathione, a correctly designed diet of organic and nutrient-dense foods, and many other therapies. We offer inpatient counseling, Equine therapy, educational components on self-care, IV and NAD treatments, and much, much more. We can help a client to boost their overall health in positive and non-invasive ways, even before the Invega withdrawal process is initiated. Some candidates will be able to safely reduce their medication to improve their quality of life and some may be able to discontinue their medication entirely if medically advised, and with an adequate length of time that can be devoted to the program.

Inpatient Invega withdrawal is done under the medical supervision of our medical team, along with our many therapists and caregivers. Please contact us directly at Alternative to Meds Center for more information on the Invega withdrawal treatment programs we offer that may benefit you or your loved one more than you thought possible.


1. FDA drug label Invega (paliperidone, paliperidone Extended Release tablets) Appr 2006 [cited 2021 July 23]

2. Marino J, English C, Caballero J, Harrington C “The role of paliperidone extended release for the treatment of bipolar disorder” NCBI, 2012 Apr 20 [cited 2021 July 23]

3. Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment optionsP T. 2014;39(9):638-645. [cited 2021 July 23]

4. Robertson S, “What is Neurotoxicity?” Life Science online N.D. [cited 2021 July 23]

5. U.S. Congress, Office of Technology Assessment, “Neurotoxicity: Identifying and Controlling Poisons of the Nervous System“, OTA-BA-436 (Washington, DC: U.S. Government Printing Office, 1990 Apr) [cited 2021 July 23]

6. Chouinard G, Samaha AN, Chouinard VA, Peretti CS, Kanahara N, Takase M, Iyo M. Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Psychother Psychosom. 2017;86(4):189-219. doi: 10.1159/000477313. Epub 2017 Jun 24. PMID: 28647739. [cited 2021 July 23]

7. Thompson IA, de Vries EFJ, Sommer IEC. Dopamine D2 up-regulation in psychosis patients after antipsychotic drug treatment. Curr Opin Psychiatry. 2020 May;33(3):200-205. doi: 10.1097/YCO.0000000000000598. PMID: 32049767. [cited 2021 July 23]

8. CAMH authors, “Antipsychotic Medication”  Health Information Letter [online] ND [cited 2021 July 23]

9. Ulysses contractOxford Reference. Retrieved 21 Jul. 2021, from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803110554741 [cited 2021 July 23]

10. Larsen-Barr M, Seymour F, Read J, Gibson K. Attempting to discontinue antipsychotic medication: Withdrawal methods, relapse and success. Psychiatry Res. 2018 Dec;270:365-374. doi: 10.1016/j.psychres.2018.10.001. Epub 2018 Oct 1. PMID: 30300866. [cited 2021 July 23]

11. Vasan S, Padhy RK. Tardive Dyskinesia. [Updated 2021 May 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK448207/ [cited 2021 July 23]

12. Ware MR, Feller DB, Hall KL. Neuroleptic Malignant Syndrome: Diagnosis and Management. Prim Care Companion CNS Disord. 2018 Jan 4;20(1):17r02185. doi: 10.4088/PCC.17r02185. PMID: 29325237.[cited 2021 July 23]

13. Pileggi DJ, Cook AM. Neuroleptic Malignant Syndrome. Ann Pharmacother. 2016 Nov;50(11):973-981. doi: 10.1177/1060028016657553. Epub 2016 Jul 19. PMID: 27423483. [cited 2021 July 23]

14. Brandt L, Bschor T, Henssler J, et al. Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis. Front Psychiatry. 2020;11:569912. Published 2020 Sep 29. doi:10.3389/fpsyt.2020.569912 [cited 2021 July 23]

15. AFP Journal (Australian Family Physician) “Beyond anxiety and agitation: A clinical approach to akathisia.”  Volume 46 No 5 2017 pages 296-298 [cited 2021 July 23]

16. Keks N, Schwartz D, Hope J. Stopping and switching antipsychotic drugsAust Prescr. 2019;42(5):152-157. doi:10.18773/austprescr.2019.052 [cited 2021 July 23]

17. Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia?. World Psychiatry. 2018;17(2):149-160. doi:10.1002/wps.20516 [cited 2021 July 23]

18. McKeown NJ, Bryan JH, Horowitz BZ. Catatonia associated with initiating paliperidone treatmentWest J Emerg Med. 2010;11(2):186-188. [cited 2021 July 23]

19. Duggal HS, Singh I. Drug-induced catatonia. Drugs Today (Barc). 2005 Sep;41(9):599-607. doi: 10.1358/dot.2005.41.9.899610. PMID: 16341291. [cited 2021 July 23]

20. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018;17(3):341-356. doi:10.1002/wps.20567 [cited 2021 July 23]

21. Tunbridge EM, Harrison PJ, Weinberger DR. Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol Psychiatry. 2006 Jul 15;60(2):141-51. doi: 10.1016/j.biopsych.2005.10.024. Epub 2006 Feb 14. PMID: 16476412. [cited 2021 July 23]

22. Mueser, Kim Tornvall, and Dilip V. Jeste, eds. Clinical handbook of schizophrenia. Guilford Press, 2011. [cited 2021 July 23]

23. Henquet C, Rosa A, Krabbendam L, Papiol S, Fananás L, Drukker M, Ramaekers JG, van Os J. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 2006 Dec;31(12):2748-57. doi: 10.1038/sj.npp.1301197. Epub 2006 Aug 23. PMID: 16936704. [cited 2021 July 23]

24. Corena-McLeod M. Comparative Pharmacology of Risperidone and Paliperidone. Drugs R D. 2015 Jun;15(2):163-74. doi: 10.1007/s40268-015-0092-x. PMID: 25943458; PMCID: PMC4488186. [cited 2021 July 23]

25. Helland A, Spigset O. Serum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation. Ther Drug Monit. 2017;39(6):659-662. doi:10.1097/FTD.0000000000000457 [cited 2021 July 23]

26. Janicak PG, Winans EA. Paliperidone ER: a review of the clinical trial dataNeuropsychiatr Dis Treat. 2007;3(6):869-897. doi:10.2147/ndt.s1365 [cited 2021 July 23]  [cited 2021 July 23]


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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Invega Withdrawal Symptoms, Paliperidone Side Effects, Treatment Help
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