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Effectiveness of low-dose doxycycline (LDD) on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study

Hubertus Seitsalo12, Raija K Niemelä3, Magdalena Marinescu-Gava1, Tuija Vuotila1, Leo Tjäderhane4* and Tuula Salo12

Author Affiliations

1 Institute of Dentistry, University of Oulu, PO BOX 5281, 90014 Oulu, Finland

2 Oulu University Hospital (OUH), PO Box 50, 90029 OYS, Finland

3 Division of Rheumatology, Department of Internal Medicine, Oulu University Hospital (OUH), PO Box 20, 90029 OYS, Finland

4 Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital (HUCH), PO BOX 14, 00014 University of Helsinki, Finland

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Journal of Negative Results in BioMedicine 2007, 6:11  doi:10.1186/1477-5751-6-11

Published: 31 December 2007



Matrix metalloproteinases (MMPs) are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS). Low-dose doxycycline (LDD) inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients.

This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately.


Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p < 0.05). The differences may, however, reflect normal fluctuation of symptoms in SS patients.


LDD may not be useful in reducing the primary SS symptoms.