Controlled, double-blind trials

Selective COX-2 inhibitors are ideal agents to combine with chemoradiotherapy for several reasons. First, they have been shown to enhance the effect of various chemotherapeutic agents and radiation on cancer cells. Second, selective COX-2 inhibitors are relatively safe. They do not have severe gastrointestinal toxicity, which is common in many nonselective NSAIDs. For example, celecoxib, a selective COX-2 inhibitor which is currently being used for patients with arthritis, is 375-fold more selective for COX-2 compared to COX-1 (94), and in large randomized, multicenter, placebo-controlled, double-blind trials conducted in patients with rheumatoid arthritis, celecoxib proved to be less toxic than nonselective inhibitors of COX-1 and COX-2, and no more toxic than a placebo (95). Third, high-dose celecoxib (600 mg bid) has no effect on serum thromboxane or platelet function (96). This is obviously important in patients receiving... 

Fluoxetine Bulimia Netvosa Collabotative Study Group (1992) Fluoxetine in the tteatment of bulimia netvosa a multicentet, placebo-controlled, double-blind trial. Arch Gen Psychiatry 49 139-147. 

The panicogenic effects of CCK-B agonists and the ability of CCK-B antagonists to block this effect raise the question of therapeutic efficacy of CCK-B antagonists on spontaneous panic attacks. Thus far, the only clinical trial carried out is inconclusive. Kramer and colleagues [1995] used a multicenter, placebo-controlled, double-blind trial to investigate the efficacy of L-365,260 [30 mg four times a day] in patients with panic disorder with or... 

Arana GW, Baldessarini RJ, Ornsteen M The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42 1193-1204, 1985 Arana GW, Santos AB, Laraia EA Dexamethasone for the treatment of depression a randomized, placebo-controlled, double-blind trial. Am J Psychiatry 152 265-267, 1995... 

Chambers CA, Bain J, Rosbottom R, et al Carbamazepine in senile dementia and overactivity—a placebo controlled double blind trial. IRCS Med Sci 10 505-506, 1982... 

London E, Fanelh RJ, Kimes A, et al Effects of chronic nicotine on cerebral glucose utilization in the rat. Brain Res 520 208-214, 1990 Lonnqvist J, Sihvo S, Syvalahti E, et al Moclobemide and fluoxetine in atypical depression a double-blind trial. J Affect Disord 32 169-177, 1994 Loo H, Malka R, Defance R, et al Tianeptine and amitriptyline controlled double-blind trial in depressed alcoholic patients. Neuropsychobiology 19 79-85, 1988... 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Mitchell JE, Groat RA. A placebo-controlled, double-blind trial of amitriptyline in bulimia. J Clin Psychopharmacoi 1984 4 186-193. 

One controlled, double-blind trial plus anecdotal evidence attest to the efficacy of chlorambucil in rheumatoid arthritis. Chlorambucil has also been used in Behef s disease, systemic lupus erythematosus, vasculitis, and other autoimmune disorders. 

Marx N, Wohrle J, Nusser T et al. Pioglitazone reduces neointima volume after coronary stent implantation a randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation 2005 I 12 2792-2798. 

Duinkerke SJ, Botter PA, Jansen AA, van Dongen PA, van Haaften AJ, Boom AJ, van Laarhoven JH, Busard HL (1993) Ritanserin, a selective 5-ht2/lc antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry... 

The results of a 1-year open extension of two randomized, double-blind studies of zaleplon have been reported (9). In 316 older patients who took zaleplon nightly from 6 to 12 months and were then followed through a 7-day singleblind, placebo-controlled, run-out period, the safety profile was similar to that observed in a short-term trial in an equivalent population. The data also suggested that therapy for up to 12 months produced and maintained statistically significant improvement in time to persistent sleep onset, duration of sleep, and the number of nocturnal wakenings. Withdrawal was not associated with rebound insomnia. The authors concluded that placebo-controlled, double-blind trials are needed to confirm these results. 

A small, controlled, double-blind trial showed topical acyclovir is insufficient for severe ocular inflammation. Topical steroids alone were effective but needed prolonged treatment times. Combined topical acyclovir and steroids were better than steroids alone and resulted in fewer rebound inflammations (Marsh and Cooper). 

Selegiline may have anti-oxidant and anti-apoptotic properties in addition to inhibiting MAO, and has been reported to increase SOD activity in the basal ganglia of rats (Knoll, 1989). There have been several duals of selegiline 10mg per day in patients with ALS a randomized, placebo controlled, double blind trial (Lange et al., 1998), and a placebo-con trolled crossover trial (Mitchell et al., 1995). Neither showed improvement in functional or subjective rating scales, but both trials were underpowered due to insufficient sample size and so may be considered inconclusive. 

Sherman, K.E., Sjogren, M., Creager, R.L., Damiano, M.A., Freeman, St., Lewey, S., Davis, D., Root, S., Weber, F.L., Ishak, K.G., Goodman, ZJ>. Combination therapy with thymosin al and interferon for the treatment of chronic hepatitis C infection a randomized, placebo-controlled double-blind trial. Hepatology 1998 27 1128—1135... 

Gonciarz, Z., Besser, R, Lelek, E., Gundermann, K.J., Johannes, K.J. Randomized placebo-controlled double blind trial on essential phospholipids in the treatment of fatty liver associated with diabetes. Med. Chir. Dig. 1988 17 61-65... 

Simons M, Schwarzler F, Lutjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer s disease A 26 week randomized, placebo controlled, double blind trial. Ann Neurol 52 346-350. 

Gotoh F, Tohgi H, Hirai S, Terashi A, Fukuuchi Y, Otomo E, Shinohara Y, Itoh E, Matsuda T, Sawada T, Yamaguchi T, Nishimaru K, Ohashi Y. Cilostazol stroke prevention study a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis 2000 9 147-57. 

Schneider NG, Olmstead R, Mody FV, Doan K, Franzon M, Jarvik ME, Steinberg C. Efficacy of a nicotine nasal spray in smoking cessation a placebo-controlled, double-blind trial. Addiction 1995 90(12) 1671-82. 

Altomare DF, Rinaldi M, Milito G, Arcana F, Spinelli F, Nardelli N, Scardigno D, Pulvirenti-D Urso A, Bottini C, Pescatori M, Lovreglio R. Glyceryl trinitrate for chronic anal fissure—healing or headache Results of a multicenter, randomized, placebo-controled, double-blind trial. Dis Colon Rectum 2000 43(2) 174-81. 

Laine L, ComineUi F, Sloane R, Casini-Raggi V, Marin-Sorensen M, Weinstein WM. Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production a controlled double-blind trial. Aliment Pharmacol Ther 1995 9(2) 127-35. 

The effects of modified-release oxycodone in osteo-arthritic pain have been evaluated in a placebo-controlled, double-blind trial in 133 patients (2). Oxycodone was effective, and although opioid-related adverse effects were frequent they were considered acceptable by the authors. 

Hsu CY, Norris JW, Hogan EL, Bladin P, Dinsdale HB, Yatsu FM, Earnest MP, Scheinberg P, Caplan LR, Karp HR. Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial. Stroke 1988 19(6) 716-22. 

Sorensen T S, Sorensen A I, Strange K 1991 The effect of intraarticular instillation of bupivacaine on postarthroscopic morbidity a placebo-controlled, double-blind trial. Arthroscopy 7 364-367... 

Rejali D, Sivakumar A, Balaji N. Ginkgo biloba does not benefit patients with tinnitus a randomized placebo-controlled double-blind trial and meta-analysis of randomized trials. Clin Otolaryngol 2004 29 226-231. 

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