Low-Dose Naltrexone in Sjogren’s Syndrome

Low-Dose Naltrexone in Sjogren’s Syndrome

What is Sjogren’s Syndrome?

Sjogren’s Syndrome (SS) is a chronic inflammatory autoimmune disorder with an unknown cause. The autoimmune aspect of the condition causes immune cells to attack tear ducts and salivary glands specifically, causing hallmark symptoms of the disease called sicca symptoms. Sjogren’s Syndrome can be classified as either primary Sjogren’s Syndrome or secondary Sjogren’s Syndrome, the difference between the two being that secondary SS coexists with another autoimmune disease such as lupus, rheumatoid arthritis, systemic sclerosis, or multiple sclerosis.

Sjogren’s Syndrome is a relatively uncommon disease, with the worldwide prevalence around 0.1 to 4.8%. That being said, there are several populations associated with higher rates of SS, including those residing in Europe, women, and an age around 50 years old. Additionally, secondary SS is more common than primary SS.

What are common symptoms of Sjogren’s Syndrome?

The encouraging aspect of Sjogren’s Syndrome is that 90% of patients have a benign disease course. This being said, symptoms of SS are lifelong and can impact patients’ quality of life dramatically. As stated previously, sicca symptoms are the most common manifestation of SS, occurring in up to 98% of patients. Sicca symptoms are generally classified by body area, including:

Keratoconjunctivitis sicca
  • Foreign-body sensation (feeling of an object or dust in the eye)
  • Burning or soreness in the eyes
  • Increased sensitivity to light
Xerostomia sicca
  • Dry mouth
  • Difficulty speaking for extended periods of time and chewing dry food due to dry mouth
  • Consequences:
    • Higher prevalence of cavities and early tooth loss
    • Recurrent oral Candida (fungal) infections
Dry skin
  • Dry skin with itchiness
Dryness of upper respiratory tract
  • Increased incidence of infection like bronchitis
  • Dry cough
  • Dryness of vaginal area

Sjogren’s Syndrome is not only limited to dryness of glands and mucous membranes, but often presents with body-wide symptoms of autoimmune disease. Common general symptoms include:

  • Fatigue
  • Diffuse pain
  • Arthralgia (joint pains or aches)
  • Raynaud’s phenomenon (poor circulation leading to white or blue fingertips or toes when exposed to cold or stress)
  • Skin conditions including vasculitis (inflammation of blood vessels) in the legs, redness, or purple spots
  • Sensory neuropathy (feeling of tingling or numbness)

What are treatment options for Sjogren’s Syndrome?

Sjogren’s Syndrome is managed on an individual basis, based on the patient’s symptoms and disease activity. Patients with body-wide symptoms as described above may be given disease-modifying therapy, while those with SS limited to sicca symptoms will likely be treated with therapies targeted to their symptoms. Treatment for specific sicca symptoms are listed below:

All patients with sicca symptoms Behavioral modifications
  • Air humidification
  • Fluoride for cavity prevention
  • Smoking cessation
  • Proper sleep hygiene
  • Aerobic fitness
Keratoconjunctivitis sicca
  • Artificial tears with an eye lubricant
  • Pilocarpine
  • Cevimeline
  • Cyclosporine
  • Punctal plugs
  • Scleral lenses
Xerostomia sicca
  • Topical fluorides
  • Pilocarpine
  • Saliva substitutes, sugar-free gum
Rhinitis sicca
  • Nasal oil
Bronchitis sicca
  • Pilocarpine
  • Bromhexine
  • Inhalation with saline
  • Estrogen-containing vaginal suppository

As mentioned previously, patients with generalized or body-wide symptoms of SS will likely be prescribed disease-modifying therapy. Generally, choice of medication is based on the patient’s coexisting diseases, such as lupus or MS. One medication that is used commonly for SS is hydroxychloroquine, which has proven to be effective in patients with mild to moderate symptoms of SS, such as arthralgia, skin conditions, or fatigue. For patients with severe manifestations, high-dose methylprednisolone and cyclophosphamide may be prescribed. More recently, Low-Dose Naltrexone (LDN) has been studied for patients with Sjogren’s Syndrome, as described below.

What is Low-Dose Naltrexone?

Although naltrexone is typically thought of as a treatment of opioid use disorder or alcoholism, Low-Dose Naltrexone (LDN) has completely different uses and effects when taken at low doses generally between 0.5 to 6 mg daily. LDN has shown pain relief and antiinflammatory properties not reported at higher doses, paving the way for its use in a multitude of pain, inflammatory, and autoimmune conditions. The way in which LDN reduces inflammation is thought to be by inhibition of immune cells in the brain called microglia, which release inflammatory markers when activated. Over time, inflammatory markers can contribute to body-wide sickness, manifesting as pain sensitivity, fatigue, sleep disorders, mood disorders, and general feelings of malaise. This is the proposed mechanism of LDN in Sjogren’s Syndrome, as LDN has been shown to reduce inflammation in patients with SS. For more information on how LDN works and its uses for other conditions, please see the post “Low-Dose Naltrexone Patient Information”.

How is Low-Dose Naltrexone used in Sjogren’s Syndrome?

The current data for the use of LDN for Sjogren’s Syndrome is limited to case reports only. These case reports, though, are encouraging for LDN’s potential utility in the disease. There are three case reports that detail LDN use in SS, in which all patients are female and have diagnosed SS with symptoms of dry eyes and mouth, joint pain, fatigue, and general pain. Additionally, all patients had elevated inflammatory markers prior to initiating LDN. These three patients started LDN at differing doses, ranging from 0.5 mg to 1.5 mg, and titrated up to final doses ranging from 2 mg to 8.5 mg. All patients reported significant improvements in their feelings of wellness, resolution of joint or general body pain, and decreased inflammatory markers on laboratory examination. Taken together, these case reports illustrate the promising potential role of LDN in Sjogren’s Syndrome. It is important to note, though, that LDN does not affect sicca symptoms, and all patients reported no change with regard to their eye and mouth dryness.


  1. Stefanski AL, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T. The Diagnosis and Treatment of Sjögren`s Syndrome. Dtsch Arztebl Int. 2017;114(20):354-361.
  2. Mavragani CP, Moutsopoulos HM. Sjögren syndrome. CMAJ. 2014;186(15):E579-E586.
  3. Naltrexone (Revia) [package insert]. Duramed Pharmaceuticals, Inc: Pomona, NY. 2013.
  4. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014;33(4):451-459.
  5. Kim, P.S., Fishman, M.A. Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review. Curr Pain Headache Rep. 2020;42(64):1-8.
  6. Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF. Norman cousins lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun. 2007;21(2):131–146.
  7. McCusker RH, Kelley KW. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol. 2013;216(Pt 1):84–98.
  8. Perrot S. Fibromyalgia syndrome: a relevant recent construction of an ancient condition? Curr Opin Support Palliat Care. 2008;2(2):122-7.
  9. Okun E, Griffioen KJ, Mattson MP. Toll-like receptor signaling in neural plasticity and disease. Trends Neurosci. 2011;34:269–81.
  10. Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007;21(2):153-60.
  11. Myers JS. Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms. Oncol Nurs Forum. 2008;35(5):802–7.
  12. Zashin S. Sjogren`s Syndrome: Clinical Benefits of Low-dose Naltrexone Therapy. Cureus. 2019;11(3):e4225.
  13. Zashin S. Sjogren`s Syndrome and Clinical Benefits of Low-Dose Naltrexone Therapy: Additional Case Reports. Cureus. 2020;12(7):e8948.