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Loxapine Withdrawal Safety Tips, Guidance

Last Updated on October 28, 2022 by Diane Ridaeus

Alternative to Meds Editorial Team
Medically Reviewed by Dr Michael Loes MD

Persons electing Loxapine withdrawal should be afforded expert care and compassion throughout the process. Coming off antipsychotic medication is unfamiliar territory for much of the rehab world. Aim to find help that is coming from knowledge and familiarity for your best and safest outcome.1,19

We have assisted many clients in completely discontinuing antipsychotics. However, we understand that not all persons will be able to completely discontinue loxapine therapy. Nonetheless, reduction down to the smallest dosage to control symptoms, while maintaining an improved overall quality of life is very much a worthy goal to strive for.


adhd medication withdrawal

Do Your Symptoms Require Loxapine?

Alternative to Meds Center offers a wide range of antipsychotic withdrawal and holistic mental health services. Please take a moment to review an independent report documenting our treatment success over the last 2 decades. Our approach to loxapine withdrawal is based on the fundamentals of safety and comfort. We have found that in many cases, symptoms can be addressed using holistic, nontoxic protocols. We also investigate root causes for original symptoms and search for medical and other factors that may have been missed, or that may have changed since a person’s original diagnosis.

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About Loxapine

loxapineIn 1975 Loxitane© (loxapine succinate) capsule formulation came out, offering a new choice in first-generation antipsychotic medications. While its molecular structure is nearly identical to clozapine, a second-generation or “atypical” medication, loxapine was found less associated with heart injuries than other antipsychotics, and less likely to cause the drooling effect that can make antipsychotic therapy undesirable. Neither loxapine nor clozapine are considered 1st-line treatments but are turned to when other treatments were found unsatisfactory.  Loxapine has been described as having some “second-generation” characteristics, though it is classed as a “first-generation” or “typical” antipsychotic. 1,7,23

Since 1975 new versions have been produced including an oral liquid version, (Loxitane C©), an injectable form, (Loxitane IM©), and an inhalent powder form of loxapine, (Adasuve©). Audsuve is an extremely fast-acting drug (less than 10 minutes) used to quell high-level agitation in persons with schizophrenia that could endanger one’s own or another’s life. Loxapine is not approved for dementia patients presenting with agitation.1,13

All antipsychotic medications can cause adverse effects which can begin to outweigh the benefits for an individual. The phenomenon known as medication tolerance, where the drug stops working, is another challenge in treatment. Although loxapine may have been the correct treatment option at the time of a severe crisis, after a patient has stabilized, it may be time to consider other treatment options.

A diagnosis of schizophrenia and similar disorders has been confounded by many factors historically, including a poor understanding of the causes of the condition, often resulting in misdiagnosis, and failed treatment methods. Once viewed as a life-long physical deterioration of the brain, modern research has illuminated a more complete understanding of schizophrenia and psychosis, and how risk factors such as diet, toxin exposures, genetic factors, marijuana use, childhood trauma, and others can precipitate such disorders. 3,5,8 

Loxapine withdrawal may be an opportunity to initiate a treatment plan that can make more effective treatment options possible. We believe antipsychotic withdrawal is best done in an attentive and medically monitored setting to ensure the safety and comfort of the patient. Adequate support must also be in place to allow for a comprehensive and effective horizon of treatment. Completely eliminating antipsychotic medication may take a considerable amount of time, months, or even years, and should always be done with competent medical support, adequate therapies, and compassionate guidance. 4,6

Loxapine Withdrawal and Neuroadaptation

Antipsychotic drugs influence certain chemical receptors located in the brain and CNS. An antipsychotic drug is thought to act something like a tap, so the expression of certain (natural) chemicals can be shut down or decreased. To compare, in stimulants, the tap might be opened to increase the flow of certain neurotransmitters. In the case of psychosis and symptoms of schizophrenia, restricting dopamine expression is the job of antipsychotic medication.

loxapine neuroadaptationDepending on the drug, different receptors may be affected. In the case of loxapine, dopamine and possibly others are disabled, or changed, resulting in calming sedation, and quieting unwanted symptoms such as hallucinations, and agitation. By contrast, a torrent of chemicals is unleashed when an antipsychotic drug is withdrawn too abruptly. The faster the withdrawal, the worse the gush. You want to go slow and avoid such an overwhelming catastrophe.

As with all antipsychotic medications, loxapine withdrawal (especially when attempted too quickly) is commonly associated with rebound symptoms that can be as intense or more intense than the original symptoms prior to medication. We have found that this tendency is primarily seen where the withdrawal is too fast, and most commonly, where preparation steps have been omitted or skimped. More information on preparing for loxapine withdrawal is given further on in this article.

In addition to rebound symptoms, antipsychotic withdrawal symptoms in general can be identified as newly emerging symptoms that were not present during drug treatment. The mechanics of how and why withdrawal symptoms occur is not fully understood, but the general consensus is that neuroadaptation plays a major role. Neuroadaptation occurs over time, so one has to discontinue the drug slowly enough so as to not cause a catastrophe of rebound or other symptoms.9,10

Loxapine Withdrawal Symptoms

After a medication like loxapine has been taken for a substantial period of time, neuroadaptation is a recognized outcome. Although more research is ongoing on neuroadaptation during drug therapy, it is likely an underlying reason for loxapine withdrawal symptoms, that can be made less intense through gradual cessation, rather than abruptly stopping. The neurochemistry does need adequate time to adjust and normalize after the effects of the medication have developed.

Loxapine withdrawal symptoms can include:
  • loxapine withdrawal symptomsHyperkinesia, abnormal movement disorders
  • Nausea and vomiting
  • Abdominal pain
  • Diarrhea
  • Headache
  • Tachycardia
  • Vertigo, dizziness
  • Excess sweating
  • Dry mucous membranes, runny nose
  • Aching muscles
  • Restlessness
  • Agitation
  • Tension
  • Insomnia, nightmares
  • Numbness
  • Infants born to mothers taking loxapine (all versions) may also experience withdrawals that include agitation, respiratory distress, stiff or weak muscles, feeding difficulties, tremors, and other withdrawal symptoms that may require long-term hospitalization in intensive care.1

Notes on Hyperkinesia

Hyperkinesia is a term that can include various severe movement or motor control disorders. Tardive dyskinesia is one such disorder that is a drug-induced condition. Antipsychotics can cause tardive dyskinesia, especially the 1st generation type. Research has found there is reduced (but not eliminated) potential in 2nd generation antipsychotics for such involuntary movement disorders.11,14

Tardive dyskinesia is typically considered an irreversible condition. However, a study published by the Journal of World Psychiatry reviewed strong evidence that administering a standardized extract of ginkgo Biloba significantly lessened or reversed tardive dyskinesia symptoms. An outstanding 96% of participants completed the placebo-controlled trial, showing the treatment was well-tolerated by the over 150 participants who were suffering from tardive dyskinesia. Other holistic measures were also reported to have preventative effects on further deterioration of tardive dyskinesia, such as vitamin B6, and vitamin E. These types of holistic treatments may be meaningful for persons considering the safest and best outcome for their loxapine withdrawal protocols.16-19

What is Loxapine Prescribed to Treat?

The inhalant version of loxapine, Adasuve, was approved in 1975 to treat agitation associated with schizophrenia or Bipolar 1. Adasuve can only be given by a medical professional in an enrolled healthcare facility, and only once in any 24-hour period. Sedation effects are typically observed quickly, within a few minutes. Other versions of loxapine including the intramuscular injectable, liquid, and capsule formulations are approved to treat schizophrenia, but not in comatose patients or those with a drug or alcohol-induced severely depressed state. Sedation effects begin after 20 minutes, peaking at around 3 hours, and last for 12 hours.1-3

Because of the increased risk of death, loxapine is not approved for dementia patients presenting with agitation or other symptoms. The powder (inhalant) version should not be used in patients with a history of asthma or bronchial issues to avoid constriction of the airway (bronchospasm). For one hour after a dose of Adasuve is given, the patient should be monitored every 15 minutes for signs of bronchospasm or airway constriction whether or not a history of bronchial issues exists.15

Strategies and Safety Tips for Loxapine Withdrawal

loxapine withdrawal tipsIn loxapine withdrawal there can be significant shifts in neurochemistry, involving dopamine, prolactin, and other hormones that can wildly fluctuate. These dysregulations can be assisted by several strategies, some examples of which are outlined below.

Contract for Safety:  Before discontinuing antipsychotic medication, it is recommended to draw up an agreement with your caregivers so that if there is resistance to following the “doctor’s orders” there is an understanding that hospitalization or the police may have to become involved. When antipsychotic medication is reduced, there can be a surge of excitatory neurochemicals that may cause a person to feel SO good, that the person decides to hurry up the process by skipping doses or making more extreme reductions. This can be a road to disaster and needs to be carefully kept in check.

Gradual cessation, not abrupt cessation:  Loxapine withdrawal must be gradual and may take a considerable length of time for success. Realize that if withdrawals become too unmanageable, it may be necessary to reinstate at a higher dosage to a point of stabilization, and then resume the slow and gradual cessation process.

Be at a stable point before withdrawal:  A person should be stable, that is, eating well, sleeping well, and not experiencing psychosis, hallucinations, rages, or other symptoms, before beginning to reduce medication. At any point where the dosage is cut, seek a point of stability before the next reduction is made. Let your prescriber and medical care team know what you are experiencing so such changes can be promptly addressed as you progress through the process.

substance withdrawal requires excellent nutritionPay attention to diet:  Clinical research has shown that adhering to a diet that includes adequate Omega-3 fatty acids, quality protein, clean (chemical-free) vegetables and fruit, and food choices that generally follow the Mediterranean diet can be a significant help in recovery. Getting tested for nutritional deficiencies is recommended, and supplements may be useful to correct such issues. Fermented foods are helpful such as sauerkraut and yogurt to replenish the gut microbiome, essential for mental wellness. Eliminate sugars and artificial sweeteners, caffeine, gluten, additives, and flavor enhancers. Gluten is especially important to avoid as an association between gluten and schizophrenia has been demonstrated in clinical research. Also, avoid refined carbs including white flour and white rice, and eliminate processed food products.18-20 These and other evidence-based recommendations can be found on our Orthomolecular Medicine pages. Be sure to discuss changes to your diet with your prescribing physician.

Cleansing/preventing accumulations of neurotoxins:  In our modern world we are bombarded with toxic chemicals such as insecticides, heavy metals, cleaning products, and other toxic agents. Research has demonstrated a clear association between psychiatric symptoms and exposure to poisons in the environment and from the workplace, and in military situations. Clear toxic substances from the home, and use nontoxic personal products and cleaning products to avoid further exposures. Alternative to Meds Center utilizes safe and gentle neurotoxin removal protocols as part of a program for loxapine withdrawal.21-23

Loxapine Withdrawal at Alternative to Meds Center

The services offered at Alternative to Meds Center are all evidence-based, and programs are designed on an individual basis for recovery of natural mental health. Please visit our services pages to review all of the therapies and services available to you during your stay with us.

We have helped thousands of clients over the last 17 years to reach their health goals. Whether your goal is to completely eliminate medication or reduce it to a more manageable level, we are ready to assist you safely and effectively. Please call us for more details about how our loxapine withdrawal and reduction programs may be the kind of help you have been searching for.

1 (800) 301-3753 for Loxapine Withdrawal Help

1. FDA label Adasuve (loxapine inhalation powder) first approved 1975 [cited 2022 Oct 28]

2. FDA label Loxitane (loxapine succinate) capsules, oral concentrate, and IM intramuscular formats) first approval 1975, recently revised Feb 2017 [cited 2022 Oct 28]

3. Citrome L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder: focus on inhaled loxapine as an alternative to injectable agents. Ther Clin Risk Manag. 2013;9:235-45. doi: 10.2147/TCRM.S31484. Epub 2013 May 20. PMID: 23723707; PMCID: PMC3665578. [cited 2022 Oct 28]

4.  Horowitz MA, et al, Method for Tapering AntipsychoticTreatment That May Minimize the Risk of Relapse Schizophrenia Journal Bulletin 47, Issue 4, July 2021, pages 1116-1129  [cited 2022 Oct 28]

5.  Hany M, Rehman B, Azhar Y, Chapman J. Schizophrenia. 2022 Aug 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30969686. [cited 2022 Oct 28]

6. Popovic D, Nuss P, Vieta E. Revisiting loxapine: a systematic review. Ann Gen Psychiatry. 2015 Apr 1;14:15. doi: 10.1186/s12991-015-0053-3. PMID: 25859275; PMCID: PMC4391595. [cited 2022 Oct 28]

7. Shrestha S, Agha RS, Khan Z, Shah K, Jain S. Considering Loxapine Instead of Clozapine: A Case Series and Literature Review. Cureus. 2021 Jan 26;13(1):e12919. doi: 10.7759/cureus.12919. PMID: 33654602; PMCID: PMC7906363. [cited 2022 Oct 28]

8. Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. Geneva: World Health Organization; 2009. 4, Withdrawal Management. Available from: https://www.ncbi.nlm.nih.gov/books/NBK310652/  [cited 2022 Oct 28]

9. Brandt L, Bschor T, Henssler J, Müller M, Hasan A, Heinz A, Gutwinski S. Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis. Front Psychiatry. 2020 Sep 29;11:569912. doi: 10.3389/fpsyt.2020.569912. PMID: 33132934; PMCID: PMC7552943. [cited 2022 Oct 28]

10. Amato D, Beasley CL, Hahn MK, Vernon AC. Neuroadaptations to antipsychotic drugs: Insights from pre-clinical and human post-mortem studies. Neurosci Biobehav Rev. 2017 May;76(Pt B):317-335. doi: 10.1016/j.neubiorev.2016.10.004. Epub 2016 Oct 15. PMID: 27756689. [cited 2022 Oct 28]

11. Caroff SN. Recent Advances in the Pharmacology of Tardive Dyskinesia. Clin Psychopharmacol Neurosci. 2020 Nov 30;18(4):493-506. doi: 10.9758/cpn.2020.18.4.493. PMID: 33124584; PMCID: PMC7609206. [cited 2022 Oct 28]

12. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. PMID: 11873706. [cited 2022 Oct 28]

13. Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011 Jan;198(1):51-8. doi: 10.1192/bjp.bp.110.081513. PMID: 21200077. [cited 2022 Oct 28]

14. Caroff SN, Mann SC, Campbell EC, Sullivan KA. Movement disorders associated with atypical antipsychotic drugs. J Clin Psychiatry. 2002;63 Suppl 4:12-9. PMID: 11913670. [cited 2022 Oct 28]

15. Meeker DP, Wiedemann HP. Drug-induced bronchospasm. Clin Chest Med. 1990 Mar;11(1):163-75. PMID: 2182276. [cited 2022 Oct 28]

16. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018 Oct;17(3):341-356. doi: 10.1002/wps.20567. PMID: 30192094; PMCID: PMC6127750. [cited 2022 Oct 28]

17. Zhang WF, Tan YL, Zhang XY, Chan RC, Wu HR, Zhou DF. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 May;72(5):615-21. doi: 10.4088/JCP.09m05125yel. Epub 2010 Sep 21. PMID: 20868638. [cited 2022 Oct 28]

18. Soares-Weiser K, Maayan N, Bergman H. Vitamin E for antipsychotic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2018 Jan 17;1(1):CD000209. doi: 10.1002/14651858.CD000209.pub3. PMID: 29341067; PMCID: PMC6491331. [cited 2022 Oct 28]

19. Levinta A, Mukovozov I, Tsoutsoulas C. Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review. Adv Nutr. 2018 Nov 1;9(6):824-832. doi: 10.1093/advances/nmy056. PMID: 30325398; PMCID: PMC6247287. [cited 2022 Oct 28]

20. Brietzke E, Cerqueira RO, Mansur RB, McIntyre RS. Gluten related illnesses and severe mental disorders: a comprehensive review. Neurosci Biobehav Rev. 2018 Jan;84:368-375. doi: 10.1016/j.neubiorev.2017.08.009. Epub 2017 Aug 19. PMID: 28830676. [cited 2022 Oct 28]  

21. Brown JS Jr. Psychiatric issues in toxic exposures. Psychiatr Clin North Am. 2007 Dec;30(4):837-54. doi: 10.1016/j.psc.2007.07.004. PMID: 17938048.  [cited 2022 Oct 28]

22. Genuis SJ. Toxic causes of mental illness are overlooked. Neurotoxicology. 2008 Nov;29(6):1147-9. doi: 10.1016/j.neuro.2008.06.005. Epub 2008 Jun 24. PMID: 18621076. [cited 2022 Oct 28]

23.  Haidary HA, Padhy RK. Clozapine. [Updated 2021 Dec 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535399/ [cited 2022 Oct 28]

 

Originally Published October 27, 2022 by Diane Ridaeus


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

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.

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