Tetracycline: A Clinical Study to Determine its Effectiveness as Long-Term Adjuvant Irwin Walter Scopp,* Stuart J. Froum.f Michael Sullivan,! Gregory Kazandjian,§ David Wank| and Albert Fine|| A RANDOM DOUBLE BLIND crossover study of patients on the effects of tetracycline therapy over a 3-month period revealed that there were no significant differences between the placebo group and letracycline-treated groups in relation to (I) Gingival Index. (2) Debris Index and (3) Papillary Bleeding. A marked improvement in the Gingival Index occurred after 3 months of treatment in each group resulting from curettage and home care. Papillary bleeding was significantly reduced after 3 months of treatment in the telracycline group and similar trends were observed in the placebo group. The Debris Index in both experimental and placebo groups showed no significant change after treatment for 3 months. The data suggest that tetracycline therapy does not appreciably alter either the Gingival Index. Debris Index, or the Papillary Bleeding Index over a 3-month period. Telracycline hydrochloride is administered by some periodomists in small doses over long periods of time as adjuvant to conventional therapy. There are no studies on humans to determine the effectiveness of this regimen. It is the purpose of this study to determine whether the use of low doses of letracycline over long periods of time as adjunctive to conventional therapy is helpful. The study is a double blind crossover project on patients treated in a hospital dental service with random selection of patients receiving either tetracycline or placebo capsules. TETRACYCLINES Tetracyclines are the most frequently used agent in acne because they decrease the concentration of free fatly acids in sebum secreted to the skin surface. This treatment is suppressive rather than curative and should be reserved for those patients with inflammatory lesions. Infections caused by pneumococci can be treated with the tetracyclines when sensitivity tests indicate the presence of a susceptible strain. Similarly these drugs may be used when penicillin cannot be given to patients with gonococcal, meningococcal, or spirochetal infections. * Chief. Dental Service. Veterans Administration Medical Center, New York. NY. I(K)H), and Professor (CFT) Periodoniics; Director. Course in Medicine, New York University College of Dentistry, New York. NY 10010. t Staff Periodonlist. Veterans Administration Medical Cenier. New York, NY. 10010. 4 Resident, Veterans Administration Medical Center. New York. NY 10010 5 Periodontist, Veterans Administration Medical Center. Brooklyn. NY 10010. J Research Biochemist. Veterans Administration Medical Center. New York. New York 10010. Tetracyclines also are useful in treating mixed bacterial sinusitis. Many infections caused by Escherichia coli respond to the tetracyclines, but occasionally resistant strains emerge rapidly. The tetracyclines may be of value in certain malabsorption syndromes such as Whtpple's disease. Scopp et al.' in a double blind clinical study showed no difference between placebo and 1000 mg per day of tetracycline administered for 5 days during periodontal surgery. Epstein and Scopp" in a sensitivity study on 13 humans to determine the effectiveness of antibiotics in the management of the periodontal abscess found tetracycline to be least effective. Ciancio5 has recently published an excellent review on the use of tetracycline in dentistry including it's indications, contraindications, interactions and possible avenues for humans research. Stahl'1' ' in earlier literature suggested beneficial effects for tetracycline in long Evans strain rats showing earlier crestal bone repair following gingival injury. Shaw" indicated reversal of the periodontal syndrome in rice rats. Guggenheimer et al.' showed that approximately 70% of the patients treated for recurrent aphthous ulcers showed some improvement after receiving chlortetracycline 250 mg Q.I.D. for 5 to 7 days. Newman et al." in their work on the microbiota of periodontosis have shown that the predominately cultivable organism, a Gram-positive asaccharolytic rod. is susceptible to tetracycline. Interestingly. Crawford et a!.11 have shown in their work on the microbiota of advanced periodontitis that the predominately cultivable organism is a Gram-positive assacharolylic rod. Obviously, a discrepancy exists in the literature between the apparent beneficial effects of regaining attachment and quicker crest repair shown in animals and the 328 Volume 51 Number i> Tetracycline as Long-Term Adjuvant 329 absence of substantial benefits from tetracycline found in human studies. MATERIALS AND METHODS The study was conducted on those patients at the Veterans Administration Medical Center presenting with periodontal problems and meeting specific criteria for selection. These were: (a) Moderate to advanced periodontilis. (b) Medical clearance, and (c) Informed consent. Each patient had a thorough evaluation including an initial clinical examination, full mouth series of radiographs, standard periodontal charting, clinical photographs, oral hygiene instructions and a recording of gingival inflammation by the use of three different indices: (1) Loe & Silness Gingival Index, (2) Greene and Vermillion Debris Index, and (3) Muhlemann- Papillary Bleeding Index. The procedure consisted of random division of 20 patients into two test groups. Both groups underwent an identical clinical regime consisting of: (a) four visits of root planing and curettage under tocal anesthesia (I per quadrant) I week apart; (b) I month recall visits for 3 months periodontal chartings and record of various indices to be taken at that time. During this period one group received tetracycline and the oiher received a placebo. This was a double-blind study. Drug Regime a. First week of root planing—250 mg 4 times per day. b. 2nd week of root planing - 250 mg 3 times per day. c. 3rd week of root planing -250 mg 2 times per day. At the end of the 3-month period both groups had their medications switched and were carried on identical clinical regime for the next three months. There were 21 patients who started the study but 15 actually completed the entire regimen. At the end of the experimental procedure results were evaluated according to the various indices (Tables 1-3). Table 2 Data for Patients on I'eiraiytline Table 1 Data fur Patients on Plucelw Patient's number Gingival Index Initial 3 Months Debris Initial 3 Index Months ing Iniiial ry Bleed- Index 3 Months 7 17 20 18 n i : 3 ••) : i 2 1 14 8 16 0.3 1.4 1 A 0.3 [ i d 1 0 0.5 : ? [ - 1 9 1 1 0.9 0.7 1.2 1 2 1 ! 1 I 3 0.9 0.8 0.5 0.4 II 2 0.1 [ ) ' " 0.8 1.7 0.9 1 4 1.3 2.3 ( 1.0 < 0.75 0.9 2.7 1.2 1.4 1.8 2.o ; 1.5 1.4 ; 4 ).75 1.92 .8 .4 .8 • > .0 .0 ->) !.l i 2 0.2 0,6 1.7 !,8 2.1 2.5 4 24 22 1 7 In 4 4 5 13 6 0 7 [1. 11 in 24 4 10 9 8 2 0 (1 11 3 I 9 16 6 Patient's number Gingival Index Debris Indet Papillary Bleeding Index initial 3 Months Initial 3 Months Initial 3 Months 6 7 r 20 ].s II 12 3 " 21 : i 14 16 Table 3 Summary 1.9 1 [ 1 3 1.2 1 2 0.5 1 0 0.2 u 1 i 3 1.8 0.8 1 l 1 5 ! 3 of Data 0.3 1 .1 1 2 0.3 0.6 0.6 0.5 0.2 0 1.0 1 1 0.7 1.2 1.2 Tetracycline [N- 14) Ciingival Index 1.4 0.75 0.92 2.3 1.6 1.8 2.7 1.0 1 i) 2.0 IJ 2.2 0.5 2.2 2.8 1.3 0.9 1.4 0.75 0.9 1 6 l 2 ( i f , 1 ] 1! 1.5 0.2 1 " 2.1 26 24 4 20 25 10 g (i 0 II i : i 13 12 16 4 12 8 1 7 8 -i [i 0 1 6 ' 16 11 P l a c e b o (A' = 1 5 ) Gingival Index Av SI A\ SI Av SI Initial J mo. 1.4 0.74 0.13 0.21 (/> 0.002) Debris Initial 3 mo. 1.85 1.21 0.280 0.209 (NS) Papillary Bleeding Initial 3 mo. 16.5 7.0 2.31 1.76 (P0.0I) Av SI Av SI Av SE Iniiial 3 mo. 1.4 0.76 0.127 0.265 (P0.05) Debris Iniiial 3 mo. 1.8 1.38 0.221 0.225 iNS) Papillary Bleeding Initial 3 mo 11.1 6.9 3.5 4.8 (NS) DISCUSSION The results of the current study indicate a significant improvement in the Gingival Index and Papillary Bleeding Index following a 3 month regimen of oral hygiene instruction and root planing. These results are in agreement with previous studies.1" However, the results also indicate that these changes occurred with no significant difference between the tetracycline augmented and the placebo control group. The data indicate that when the medications were reversed the results were the same. Although researchers have suggested improved results when tetracycline was used in conjunction with conventional therapy our results do not agree with this hypothesis. Perhaps tetracycline must be administered for periods longer than 3 months to show significant results. If this is true then longer term studies should be performed. 330 Scopp, Frown, Sullivan. Kazandjian, Wank, Fine However, if comparable results can be attained with or without antibiotic augmentation then the clinician should weigh the adverse and side effects of tetracvcline before administration. REFERENCES I Scopp, I W.. I leicher. P. D.. W\man. B S . Epstein. S. R . and (•inc. A.: Tetracyclines: Double Blind Clinical Studv to Evaluate the Effectiveness in Penodontal Surgerv J Perwdonlol 48: 484, 1977. 2. Epstein, S.. and Scopp. I, W : Antibiotics and the intraoral abscess. J Periodtmtoi 48: 236. 1977 3. Ciancio. S. K: Telraeyclines and periodontal therapy. J PeriudonloiXl: 15?. 1976. 4. Stahl. S. S,: Influence of antibiotics on the healing of gingival wounds in rats II. Alveolar hond and soft tissue. J Periodontol 33: 261, 1962. 5. Stahl, S.S.: The influence of antibiotics on the healing of gingival wounds in rats II. Re-altachmenl potential of soft and calcified tissues. J Periodontol 34: IM>. 1963. J. PcriiHJonlol. June, I9K0 h. Shaw. J. H.. (jriffiths, D.. and Auskaps. A. M.: The influence of antibiotics on lhe periodonlal syndrome in rice Rats. J Dem Res 40: 511, 1961. 7. Guggenheimer. J , Brightmiin. V J , and Ship, I. I.: Effect of chlortetracyclinc m<iuih rinses on the healing of recurrent aphthous ulcers. Oral Ther 4: 4()6. 1%X, K Newman. M. C . Sotransky, S. S. Savitt, E. D , Propas. D. A., and Crawford. A.: Studies of microbiology of penodontosis. J PeriodonwiAl: 373. 1976, 9. Crawford, A,. Socransky, S. S.. and Bratihall, G.: Predominant cultivable microbiota of advanced penodontitis. Abstract No. 209. XADR 1975. HI. Tagge, D. 1... O'Leary T J.. and El-Kafrawy. A H The clinical and histological response of periodonlal pockets to root planing and oral hygiene J Ptrindonmt 46; 527, 1975. Send reprint requests lo: Dr. Irwin W. Scopp, Chief, Dental Service, Veterans Administration Medical Center. New York, NY 10010.