Placebo-controlled crossover study

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. 

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. 

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. 

The higher prevalence of tics in males and the exacerbating effects of anabolic steroids suggested the possibility that manipulation of steroid hormones might be helpful in the treatment of TS. Despite some promising case studies (Peterson et ah, 1994), however, a doubleblind, placebo-controlled, crossover study of the androgen receptor blocker flutamide, in 13 adults with TS, failed to find significant benefits (Peterson et al., 1998). 

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... 

Deprenyl. Deprenyl, a selective monoamine oxidase B inhibitor that enhances dopaminergic function, is used in the treatment of Parkinson s disease. An open-label study (Jankovic et al., 1994) suggested that deprenyl could be effective for the treatment of ADHD in children with TS. A placebo-controlled crossover study (Feigin et al., 1996) of 24 subjects with ADHD and a tic disorder found that deprenyl was safe and effective at doses ranging from 5 to 10 mg/day. Only one subject showed an increase in tics. Interpretation of these results, however, is hampered by the clear evidence of an order effect. Subjects who received active drug first showed a 37% improvement in ADHD... 

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. 

Keh, D., et al. (2003) Immunologic and hemodynamic effects of low-dose hydrocortisone in septic shock a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 167, 512-20. 

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-... 

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). 

Haloperidol is the best-studied antipsychotic medication in children and adolescents with schizophrenia. In a double-blind, placebo- and active-controlled study, haloperidol (2 to 16 mg per day) and loxapine (10 to 200 mg per day) were equally effective and superior to placebo ( 168). This finding was replicated in a placebo-controlled, crossover study of haloperidol (doses of 0.5 to 3.5 mg per day or 0.02 to 0.12 mg/kg per day) in children 5.5 to 12 years of age ( 169). In this study, haloperidol was more effective than placebo in reducing ideas of reference, persecutory ideas, hallucinations, and thought disorder. 

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. 

With increasing concern over the long-term safety of hormone replacement therapy, the benefit to harm balance has to be continually reassessed, and conclusions as to its prophylactic or therapeutic value need to be adjusted as experience accumulates. Not all the promises held out for the benefits of this therapy have been confirmed. For example, while estrogens prevent peripheral bone loss they do not prevent vertebral fractures (6) and in a 2-year placebo-controlled, crossover study in 34 healthy postmenopausal women, treatment with transder-mal estrogen alone (Menorest 50 micrograms/day) did not improve lipid profiles or any indices of arterial function (7). 

In 64 women mean age 53 years enrolled in a randomized, placebo-controlled, crossover study of desmopressin 40 micrograms by nasal spray for the treatment of severe daytime urinary incontinence, there were drug-related adverse events in 25 women taking desmopressin and 24 adverse drug reactions in 15 women taking placebo (35). The most common adverse event with desmopressin was headache (36%). Nausea occurred in 10%. 

Diamond TH, Winters J, Smith A, De Souza P, Kersley JH, Lynch WJ, Bryant C. The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade a double blind, randomized, placebo-controlled crossover study. Cancer 2001 92(6) 1444-50. 

There was an increase in blood pressure throughout 24 hours in a double-bhnd, placebo-controlled, crossover study in 47 hypertensive patients who were also taking nifedipine (10). This finding differs from other studies in which melatonin had a mild hypotensive effect (11) and may indicate an interaction between melatonin and nifedipine. Tachycardia, chest pain, and cardiac dysrhythmias have also been reported, although the relation to melatonin was not clearly established (5). 

The effects of itraconazole 100 mg on the pharmacokinetics of fluvastatin 40 mg have been studied in a randomized, placebo-controlled, crossover study in 10 healthy volunteers (9). Itraconazole had no significant effect on the Cmax or total AUC of fluvastatin, but slightly prolonged its half-life. 

More recently, Bortolotti et al. (2008) provided evidence to refute this calcium-mediated mechanism of weight loss, presenting results from a placebo-controlled crossover study of 10 obese adults with habitually low calcium intakes (<800 mg/day). Results indicated that dietary supplementation of 800 mg of calcium/day had no effect on circulating plasma free fatty acid concentrations or glycerol turnover. Theoretically, a calcium-mediated stimulation of lipolysis would have resulted in an increase in plasma free fatty acid concentrations and glycerol turnover, thus indicating a need for further research. 

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. 

Note. From B. Borcherding et al. (1990) (p. 87). Double-blind placebo-controlled crossover study. Both drugs increased likelihood of repetitious, perfectionistic, overfocused behaviors (p <. 01). MPH associated with combination of abnormal movements and OCD ADRs (p =. 009). Fourteen of the 23 (60.8%) suffered from orofacial tics or stereotypy. Twelve of the 23 had orofacial tics and 6 had stereotypy, including 4 who had both. Note the similarity to animal studies in the combination of perseveration and abnormal movements. 

These results were subsequently replicated in a double-blind, placebo-controlled crossover study (Heresco-Levy et al., 2005) in which D-serine or a placebo was added to atypical antipsychotics (risperidone... 

In a placebo-controlled, crossover study in 12 healthy men, lithium and mirtazapine had no effect on the pharmacokinetics of each other and there was no difference in psychometric testing between the addition of lithium and placebo (8). 

Drugs that potentiate serotonin function can cause ejaculatory delay in men, and this has led to the use of SSRIs to treat premature ejaculation (SEDA-26, 13). Venlafaxine is also reported to cause problems with ejaculation during routine use and its efficacy has been studied in a placebo-controlled, crossover study in 31 men with ejaculation latencies of less than 2 minutes (25). Both placebo and venlafaxine (75 mg/day of the XL formulation) significantly increased latency to ejaculation over baseline, placebo by 2 minutes and venlafaxine by 3 minutes there was no difference between the two treatments. The authors concluded that venlafaxine is not effective for the management of premature ejaculation. However, the small number of subjects studied and the large placebo effect makes this conclusion tentative. It does appear, however, that the effect of venlafaxine on ejaculation delay is probably less striking than, for example, that of paroxetine. 

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