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Loxapine Long-Term Effects | Do You Know the Warning Signs?

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

Last Updated on November 9, 2022 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

Loxapine long-term effects were not known 45 years ago when this first-generation antipsychotic medication was first marketed. But today we can access and pass on a lot more information about potential risks to watch for.

The knowledge base about schizophrenia and psychosis has also expanded considerably. The positive effects of correct diet and nutrition, as well as treating toxic exposure, trauma, and other factors in mental health have never been clearer than today. That is why these form the fundamental protocols for our clients at Alternative to Meds Center.

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Are There Risks Associated With Long-term Loxapine/Loxitane© Use?

Both conventional (1st generation, or typical) antipsychotic medications such as loxapine, and more recent (atypical, or 2nd generation) antipsychotics are associated with a doubled death rate in placebo-controlled trials. There is a black box on the packaging for all products containing loxapine (all versions) that warns against prescribing the drug to elderly dementia patients.2

Decades of studies show a number of common, well-documented adverse outcomes in the treatment of schizophrenia-related symptoms with long-term antipsychotic medications. Some of the adverse reactions to antipsychotics can be life-threatening, though these occur more rarely. Drug-induced adverse effects in general tend to increase in frequency/intensity in relation to dose escalation. The following are adverse reactions that should be monitored early in treatment.

Long-term effects of Loxapine may include:
  • loxapine serious adverse risksBrain volume loss
  • Dopamine receptor supersensitivity.
  • In some patients, worsened, prolonged, and more frequent psychotic symptoms.
  • Receptor neuroadaptation, leading to loss of medication efficacy.
  • Increased rate of major cardiovascular events,
  • More frequent relapses are associated with continuous use, compared to those who gradually came off medication.
  • Drug-induced movement disorders such as parkinsonism, tardive dyskinesia, akathisia, prolonged muscle contractions, and other extrapyramidal (involuntary muscle movement) disorders. These syndromes can manifest after low-dose, high-dose, brief use, or long-term use. A higher incidence occurs with intramuscular administration. Often these are irreversible syndromes. Some cases have reversed after discontinuation.
  • Sexual dysfunction in both male and female patients.
  • NMS (neuroleptic malignant syndrome) — a rare life-threatening reaction most associated with 1st generation antipsychotics and after an increase in dosage.
  • Lowered white blood cell count and other blood disorders.
  • Seizures.
  • Infants born to mothers taking loxapine products can suffer extrapyramidal and other adverse effects after birth.
  • CNS effects may include agitation, dizziness, fainting, shuffling gait, insomnia, tension, slurred speech, numbness, sedation, confusion, twitching, and others.
  • Puffiness, skin rash, urinary retention, constipation, alopecia (hair loss as a result of immune system dysfunction), changes in weight, and others.

After a patient stabilizes, much research in the medical literature suggests that long-term use may be unnecessary and even unwise for health reasons.1,6-15

How Exact are Diagnoses of Psychosis, Dementia, Schizophrenia, Mania, etc.?

The criteria for a diagnosis of a mental disorder like schizophrenia, psychosis, or dementia have all evolved over time. For example, most cases of dementia are decided in the office of a general practitioner, with input from family members often relied on for diagnostic criteria. Although the newest version of the DSM (V) has changed “dementia” to “neurocognitive disorder,” the term dementia is still used on drug packaging and also commonly used in the bulk of medical literature and in conversation.

how exact are psychosis diagnosesThe DSM lists a quite short list of criteria for a diagnosis of “neurocognitive disorder” which is in reality an umbrella term for various symptoms of memory loss and cognitive decline. Changes to diagnostic criteria require some effort to grasp the complexity of such a diagnosis, despite the brevity of its description in the diagnostic manual. For example, Alzheimer’s Disease is now classed as a sub-type of dementia. In addition, various psychiatric terms are used to describe different characteristics associated with a neurocognitive disorder, such as “aphasia” (the loss of language skills), “apraxia” (the inability to execute normal movements or gestures), and “agnosia” (an inability to recognize everyday objects or persons).16

This is especially concerning since neurocognitive disorder (dementia) has been described in recent medical literature as a mental health epidemic of major proportions in recent years.18

An accurate diagnosis of schizophrenia also takes a bit of time and effort to review since many aspects have been updated (and some dropped) in the DSM-V. One factor that was carried over from DSM-IV was the stipulation that hallucinations, mania, delusions, etc. cannot be attributed to substance use (prescribed or other) or to some other physiological condition. Making such a differentiation takes lab tests, medical history, and a thorough full-spectrum medical check-up, and often, in the middle of a crisis, there is no time to take such actions. And in a condition of psychosis or other distress, a cogent history may not be readily available from the patient. As a result of these and other complexities, misdiagnosis and errors in the treatment of schizophrenia, psychosis, dementia, Bipolar 1, etc., are not at all uncommon.3,5,19,20

We want you to know that Alternative to Meds Center does not focus on labels but on improving mental health naturally and safely. But we do recommend understanding more about how such a label may have been used to justify drug treatment, especially if long-term loxapine effects have caused distress instead of improved health. Knowledge can be empowering.

Prescribing Information for Loxapine

loxapine prescribing infoThere are several versions of generic loxapine that come in capsules, liquid suspension, inhalant powder, and intramuscular injectable forms.2

For immediate control of agitation, the inhalant form can be given once per 24-hour period, but only in a specially licensed facility.

The intramuscular form can be given every 4 to 6 hours to control agitation or other symptoms.

Once the patient has stabilized, and they are able to take medication orally, the label recommends transitioning to the capsule or oral concentrate form, and this switch should occur within 5 days.

Strategies to Help Loxapine Long-Term Effects

Discontinuation of antipsychotic medication can be a strategy to overcome long-term effects and regain natural mental health. But the process must be done very gradually, with adequate preparation and ongoing support in place. More information on coming off antipsychotic medication safely can be found on ATMC’s medication cessation pages.

Recovering Natural Mental Health at Alternative to Meds Center

As a short-term remedy for an extreme mental health crisis, medication may have been the best option for that situation. However, long-term loxapine use does not always provide the best possibility for recovery of mental health.

inpatient residence Alternative to Meds CenterAt Alternative to Meds Center, many therapeutic applications are used to help our clients transition to the reduction or elimination of medication. Natural substances can be used to help ease this transition, and help the neurochemistry normalize in safe, healthy ways. Clients can take advantage of neurotoxin removal, natural neurotransmitter rehabilitation, exercise including Qi Gong, yoga, and Equine Therapy, corrected diet and supplementation, CBT, IV treatments, safe discontinuation protocols under medical supervision, and a wealth of other therapeutic opportunities to restore mental wellness safely and gradually.

Perhaps you have concerns about warning signs in your or in a loved one’s situation. Please call us for more information on options for treatment. We would like to provide more details on our comfortable cessation programs and get all your questions answered, including insurance coverage, length of the program, and anything else you would like to learn more about.

Our clients express a desire to regain mental wellness in a holistic and compassionate setting under medical supervision. Our programs are designed on an individual basis for each unique person to receive such help. Over 40 trained professionals are on hand to assist, and the facility provides a warm and friendly setting, including peer support programs. Please contact us for more information about our world-class recovery program to prevent loxapine long-term effects from negatively impacting your or your loved one’s life.

1. NAMI authors, Loxapine (Adasuve) [published/reviewed online 2022 Nov] [cited 2022 Nov 8]

2. FDA Label Loxitane (loxapine succinate) capsules (loxapine hydrochloride) concentrate for oral use (loxapine hydrochloride) for intramuscular use, [first approved 1975, reviewed Feb 2017] [cited 2022 Nov 8]

3. van den Dungen P, van Marwijk HW, van der Horst HE, Moll van Charante EP, Macneil Vroomen J, van de Ven PM, van Hout HP. The accuracy of family physicians’ dementia diagnoses at different stages of dementia: a systematic review. Int J Geriatr Psychiatry. 2012 Apr;27(4):342-54. doi: 10.1002/gps.2726. Epub 2011 May 30. PMID: 21626568. [cited 2022 Nov 8]

4. Prins A, Hemke F, Pols J, Moll van Charante EP. Diagnosing dementia in Dutch general practice: a qualitative study of GPs’ practices and views. Br J Gen Pract. 2016 Jun;66(647):e416-22. doi: 10.3399/bjgp16X685237. Epub 2016 Apr 25. Erratum in: Br J Gen Pract. 2016 Aug;66(649):406. PMID: 27114209; PMCID: PMC4871307. [cited 2022 Nov 8]

5. Heckers S, et al., Structure of the Psychotic Disorders Classification in DSM-V published in Focus, the Journal of Lifelong Learning in Psychiatry [published online 2016 July 13] [cited 2022 Nov 8]

6. Goff DC, Falkai P, Fleischhacker WW, Girgis RR, Kahn RM, Uchida H, Zhao J, Lieberman JA. The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia. Am J Psychiatry. 2017 Sep 1;174(9):840-849. doi: 10.1176/appi.ajp.2017.16091016. Epub 2017 May 5. Erratum in: Am J Psychiatry. 2017 Aug 1;174(8):805. PMID: 28472900. [cited 2022 Nov 8]

7. Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry. 2011 Feb;68(2):128-37. doi: 10.1001/archgenpsychiatry.2010.199. PMID: 21300943; PMCID: PMC3476840. [cited 2022 Nov 8]

8. Martin Harrow, Thomas H. Jobe, Does Long-Term Treatment of Schizophrenia With Antipsychotic Medications Facilitate Recovery?Schizophrenia Bulletin, Volume 39, Issue 5, September 2013, Pages 962–965 [cited 2022 Nov 8]

9. Szmulewicz AG, Angriman F, Pedroso FE, Vazquez C, Martino DJ. Long-Term Antipsychotic Use and Major Cardiovascular Events: A Retrospective Cohort Study. J Clin Psychiatry. 2017 Sep/Oct;78(8):e905-e912. doi: 10.4088/JCP.16m10976. PMID: 28406267. [cited 2022 Nov 8]

10. Harrow M, Jobe TH. Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multifollow-up study. J Nerv Ment Dis. 2007 May;195(5):406-14. doi: 10.1097/01.nmd.0000253783.32338.6e. PMID: 17502806. [cited 2022 Nov 8]

11. Harrow M, Jobe TH, Faull RN. Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychol Med. 2012 Oct;42(10):2145-55. doi: 10.1017/S0033291712000220. Epub 2012 Feb 17. PMID: 22340278. [cited 2022 Nov 8]

12. Samaha AN, Seeman P, Stewart J, Rajabi H, Kapur S. “Breakthrough” dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007 Mar 14;27(11):2979-86. doi: 10.1523/JNEUROSCI.5416-06.2007. PMID: 17360921; PMCID: PMC6672560. [cited 2022 Nov 8]

13. Servonnet A, Samaha AN. Antipsychotic-evoked dopamine supersensitivity. Neuropharmacology. 2020 Feb;163:107630. doi: 10.1016/j.neuropharm.2019.05.007. Epub 2019 May 9. PMID: 31077727. [cited 2022 Nov 8]

14. 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 2022 Nov 8]

15. D’Souza RS, Hooten WM. Extrapyramidal Symptoms. [Updated 2022 Aug 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Nov 8]

16. Khaldi S, Kornreich C, Choubani Z, Gourevitch R. Antipsychotiques atypiques et syndrome malin des neuroleptiques : brève revue de la littérature [Neuroleptic malignant syndrome and atypical antipsychotics: a brief review]. Encephale. 2008 Dec;34(6):618-24. French. doi: 10.1016/j.encep.2007.11.007. Epub 2008 Apr 2. PMID: 19081460. [cited 2022 Nov 8]

17. Substance Abuse and Mental Health Services Administration. Impact of the DSM-IV to DSM-5 Changes on the National Survey on Drug Use and Health [Internet]. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2016 Jun. Table 3.22, DSM-IV to DSM-5 Schizophrenia Comparison. Available from: [cited 2022 Nov 8]

18. Beck JC, Benson DF, Scheibel AB, Spar JE, Rubenstein LZ. Dementia in the elderly: the silent epidemic. Ann Intern Med. 1982 Aug;97(2):231-41. doi: 10.7326/0003-4819-97-2-231. PMID: 7049032. [cited 2022 Nov 8]

Originally Published November 9, 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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