A Randomized, Controlled Trial of Doxycycline and Rifampin for Patients with Alzheimer’s Disease
Randomized, triple-blind, controlled trial. n = 101. JAGS, 2004.
Methods- daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months given to patients with probable AD and mild to moderate dementia.
Results- There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, ( – 2.75 points, 95% confidence interval (CI) -5.28 to -0.22, P = .034). At 12 months, the difference between groups in the SADAScog was 4.31 points (95% CI = -9.17– -0.56, P = .079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P = .34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.
Conclusion- Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD.
Observation- A trend across C. pneumoniae disease-state studies is the variability in detection of organisms using PCR and antibody tests. This has been attributed to laboratory technique variability, and traits of Chlamydia itself which has been shown to produce unreliable IgG and IgM levels from patient to patient both in the presence and absence of antimicrobial therapy. Rather than suggesting an absence of the organism, it further elucidates the need for more reliable testing methods and substantiates empiric treatment until such testing becomes available. To quote (Gerard et al. 2006) “Data from this trial did not show that attenuation of decline in psychometric parameters resulted from the effects of antibiotics, but the analyses for change in infection may have been less than fully adequate, because the sampling of antibodies and organism in blood is not always indicative of what has occurred in tissues”.
Methods- “A multicenter, blinded, randomized, 2 × 2 factorial controlled trial, set at 14 geriatric outpatient clinics in Canada. Four hundred and six patients with mild to moderate AD (standardized mini mental state examination (SMMSE) score 14–26) participated. The intervention was 12 months’ treatment with doxycycline 100 mg twice daily + rifampin 300 mg daily or doxycycline 100 mg twice daily + placebo‐rifampin daily or rifampin 300 mg daily + placebo‐doxycycline twice daily or placebo‐doxycycline twice daily + placebo‐rifampin daily. Coprimary outcomes were the Standardized Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (SADAS‐cog) and the Clinical Dementia Rating Scale‐Sum of the Boxes (CDR‐SB). Secondary outcomes were the SMMSE, Quick mild cognitive impairment screen, Geriatric Depression Scale, Cornell Scale for Depression in Dementia, activities of daily living (Lawton Scale), and the Dysfunctional Behavior Rating Instrument frequency and reaction subscales.”
Results- “There was a significant deterioration in SADAS‐cog over time with both rifampin and doxycycline in comparison with placebo. When the two were used together, there was no statistically significant decline/deterioration in comparison with placebo (n = 305). For the CDR‐SB, there were no significant effects of either rifampin or doxycycline. Secondary outcome results followed similar patterns.”
Conclusion- “Twelve months’ treatment with doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in AD.”