Double-blinded placebo-controlled crossover

Brown SG, Wiese M, Blackman K, Heddle R Ant 47 venom immunotherapy a double blind, placebo-controlled crossover trial. Lancet 2003 361 1101-1106. 

Kayumov, L., Brown, G., Jindal, R., Buttoo, K. Shapiro, C. M. (2001). A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom. Med. 63, 40-8. 

Benjamin, J., Levine, J., Fux, M. et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am. ]. Psych. 152 1084-1086,1995. 

Schwarz, E. et al., Oral administration of freshly expressed juice of Echinacea purpurea herbs fail to stimulate the nonspecific immune response in healthy young men Results of a double-blind, placebo-controlled crossover study, J Immunother, 25, 413, 2002. 

P. Jobin, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis a randomized, double-blind, placebo-controlled, crossover study. 

Peterson, B.S., Zhang, H., Bondi, C., Anderson, G.M., and Leckman, J.F. (1998b) A double-blind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette s syndrome. J Clin Psychopharmacol 18 324—331. 

In two double-blind, placebo-controlled crossover studies (Pataki et al., 1993 Rapport et al., 1993), DMI and MPH were used alone and in combination in an inpatient population to discover potential side effects. The 16 subjects, ages 7-12, had comorbid mood disorders and ADHD and received careful electocardi-... 

Willemsen-Swinkels, S.H.N., Buitelaar, J.K., and Van Engeland, H. (1996a) The effects of chronic naltrexone treatment in young autistic children a double-blind placebo-controlled crossover study. Biol Psychiatry 39 1023—1031. 

A randomized, double-blind, placebo-controlled crossover trial of botulinum toxin for the treatment of simple motor tics was conducted in 20 patients, ages 15-55, 18 of whom completed the study (Marras et al., 2001) (Table 40.2). As rated blindly on a 12-minute videotape sample, the proportional change in treated tics per minute was —39% during the botulinum toxin phase in contrast to an increase of +5.8% during the placebo phase. Half of the patients noted weakness of the injected muscles that was not functionally disabling. Two patients reported inner restlessness, accompanied by an increased urge to perform the treated tic. Two others felt that the decrease in the treated tic prompted a new replacement tic. Despite improvement in the treated tic, there was no significant evidence of overall improvement. 

Singer et al. (2001) treated 10 children, ages 8-14 years, with baclofen (20 mg, tid) in a randomized-sequence double-blind, placebo-controlled, crossover study. The mean improvement in tic severity as measured by the YGTSS total tic score was 14% for baclofen, compared with 7% worsening for placebo. This difference was not significant. When the authors evaluated the Impairment scale of the YGTSS, however. 

Desipramine. Singer et ah, (1995) compared clonidine (0.05-0.2 mg/day) and desipramine (25-100 mg/ day) in a double-blind, placebo-controlled crossover study in 37 children (ages 7-13 years old) with combined ADHD and TS. Desipramine produced a significant improvement in ADHD outcome measures and was superior to placebo. Clonidine was not different... 

Singer, H.S., Wendlandt, J., Krieger, M., and Giuliano, J. (2001) Baclofen treatment in Tourette syndrome a double-blind, placebo-controlled, crossover trial. Neurology 56 599-604. 

Antihistamines such as diphenhydramine, a mainstay of OTC sleep preparations, are also used widely by parents for their children at doses of 1 mg/kg. Most of the reports of the use of clonidine for sleep disorders are clinical and anecdotal case reports of use in children with ADFFD (Wilens et ah, 1994 Prince et ah, 1996). There are some safety concerns about using clonidine once a day at bedtime, especially in patients who take a daytime stimulant. Melatonin was studied using a double-blind, placebo-controlled, crossover design (Jan et ah, 1994) on a mixed group of 15 children with sleep disturbances, with some improvement reported. However, caution is warranted in using this agent because melatonin is unregulated, and there are concerns about the purity and safety of some commercially available preparations (Werry and Aman, 1999). 

Reid, A.D., Naylor, G.J., and Ka, D. (1981) A double-blind placebo controlled crossover trial of carbamazepine in overactive severely mentally handicapped patients. Psychol Med 11 109-113. 

Donovan, S.J., Stewart, J.W., Nunes, E.V., Quitkin, P.M., Parides, M., Daniel, W, Susser, E., and Klein, D.R. (2000) Divalproex treatment for youth with explosive temper and mood lability a double-blind, placebo-controlled crossover design. Am J Psychiatry 157 818-820. 

Hunt, R.D., Minderaa, R.B., and Cohen, D.J. (1985) Clonidine benefits children with attention deficit disorder and hyperactivity report of a double-blind placebo-controlled crossover study. / Am Acad Child Adolesc Psychiatry 24 617-629. 

Sertraline. Sertraline, the second SSRI to receive FDA approval for depression, has also been suggested as a treatment for social phobia. Katzelnick et al. (1994) carried out a double-blind, placebo-controlled, crossover study comparing sertraline and placebo. Twelve subjects were randomized to either sertraline or placebo for 12 weeks. The agent was then tapered and the subjects received no treatment for 2 weeks. They were then switched to the other treatment arm for an additional 12 weeks. Using the Liebowitz Social Anxiety Scale, analysis revealed statistically significant improvement with sertraline treatment but not with placebo. Forty-two percent of patients were rated as moderately or markedly improved while receiving the sertraline ther-... 

Benjamin J, Levine J, Fux M, et al Inositol treatment for panic disorder a double-blind placebo-controlled crossover trial. Am J Psychiatry 152 1084-1086, 1995... 

Katzelnick DJ, Jefferson JW, Greist JH, et al Sertraline in social phobia a double-blind, placebo-controlled crossover pilot study. Poster presentation at the annual meeting of the New Clinical Drug Evaluation Unit, Marco Island, FL, June... 

Broughton RJ, Fleming JA, George CF, et al Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49 444-451, 1997... 

Ravina B, Putt M, Siderowf A, et al Donepezil for dementia in Parkinson s disease a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry 76 934-939, 2005... 

A double-blind continuation study has been conducted with mirtazapine. As with venlafaxine and nefazodone, patients in this acute, double-blind, placebo- and active-controlled study with mirtazapine could remain on the double-blind treatment at the end of the initial 6-week efficacy trial and were then followed up for up to 1 year. There was a statistically significant lower risk of relapse (defined as HDRS > 16) on both mirtazapine (18%) and amitriptyline (28%) in comparison with placebo (53%), indicating that mirtazapine has maintenance efficacy (274). More recently, a 40-week, double-blind, placebo-controlled crossover study was performed with mirtazapine (275). Patients maintained on this drug had less than half the likelihood of relapsing than those patients switched to placebo (i.e., 19.7% versus 43.8%, p <0.01). 

Finally, a small, double-blind, placebo-controlled, crossover trial of fluoxetine in 14 children and adolescents with OCD also showed a significant decrease in CY-BOCS total scores (151). 

Berger CP, Presser B. Alprazolam in the treatment of two subsamples of patients with late luteal phase dysphoric disorder a double-blind, placebo-controlled crossover study. Obstet Gynecol 1994 84 379-385. 

McCleane, G.J. Intravenous infusion of phenytoin relieves neuropathic pain a randomized, double-blinded, placebo-controlled, crossover study, Anesth. Analg. 1999, 89, 985-988. 

Zakrzewska, J. M, Chaudhry, Z., Nurmikko, T. J., Patton, D. W., Mullens, E. L. Lamotrigine (lamictal) in refractory trigeminal neuralgia results from a double-blind placebo controlled crossover trial, Pain 1997, 73, 223-230. 

Flicker C., Ferris S. H., Kalkstein D., and Serby M. (1994). A double-blind, placebo-controlled crossover study of ganglioside GM treatment for Alzheimer s disease. Am. J. Psychiat. 151 126-129. 

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