Gastrointestinal symptom placebo

Four clinical phase 1 studies involving 72 healthy elderly subjects have been performed and have showed that administration of ZT-1 in humans seems to be safe and well tolerated. The incidence of possibly drug-related adverse events, in particular nervous system and gastrointestinal symptoms, was similar to placebo for doses up to 1.5 mg. An international multicenter phase II trial for dose finding and efficacy assessment, in mild-to-moderate AD patients, is underway in 28 hospitals in Europe. 

It has been suggested that the pharmacokinetics of fluvastatin, including extensive biliary excretion and absence of circulating active metabolites, might be associated with a low incidence of systemic adverse effects compared with other statins. In over 1800 patients treated for an average of 61 weeks, fluvastatin was safe and tolerable (SEDA-19, 408). Pooled data from clinical trials have shown that gastrointestinal symptoms occurred in 14% of fluvastatin recipients compared with 9% taking placebo other complaints occurred... 

In a meta-analysis of trials, there was a reduction in the duration of symptoms of about 1 day (19). Oseltamivir caused significantly more gastrointestinal symptoms (dyspepsia or nausea) than placebo the effect increased with dose. Similarly, zanamivir caused significantly more gastrointestinal symptoms than placebo (OR = 2.6 95% Cl = 1.6, 4.2). 

In a further 10 placebo-controlled trials including 492 patients on Hypericum and 455 patients on placebo, a total of 31 suspected adverse drug reactions were seen in 27 patients treated with Hypericum extract and 49 suspected adverse drug reactions were documented for 34 patients who took placebo [234, 235, 239, 240, 242, 249, 250, 251, 252]. Gastrointestinal symptoms were reported most frequently with 12 cases under Hypericum treatment and 10 cases in placebo groups. Other symptoms such as tiredness (Hypericum 2 cases, placebo 1 case), sleep disturbances (2 cases under either treatment) were very rare. 

Unspecific complaints such as gastrointestinal symptoms, tiredness and sleep disturbances are known to be frequently associated with depression. This is reflected by the finding that, in placebo-controlled trials, such symptoms have been observed as having a similar frequency in... 

A second meta-analysis, including six placebo-con-trolled red clover isoflavone trials, with doses ranging from 40 to 80 mg daily, and study duration from 12 to 16 weeks, concluded that adverse events did not differ between isoflavone and placebo groups, although the events were not well characterized in several trials. Gastrointestinal symptoms were generally the most common adverse events in both isoflavone and placebo groups (Nelson et al. 2006). 

The efficacy of combining albendazole 15 mg/kg/day for 7 days with either praziquantel 75 mg/kg/day ( = 53) or placebo n = 50) for 1 day has been studied in a double-blind, placebo-controlled, randomized study in North India in children with seizures and single-lesion neurocysticercosis [5. Repeat CT scans were performed after 1, 3, and 6 months. Seizure control and adverse reactions were similar in the two groups. Adverse effects were mild. There was no evidence of raised intracranial pressure and none of the patients reported epigastric discomfort or other gastrointestinal symptoms. None of the patients required drug withdrawal because of adverse reactions. 

Gastrointestinal symptoms such as nausea, diarrhoea and abdominal pain were the most frequently reported side effects in multiple randomized controlled trials (RCTs) and reviews [92 , 101-104 - ], although a meta-analysis did not find a significant difference from placebo in six RCTs of azithromycin in chronic lung disease - potentially due to the generally lower doses used [105 ]. 

In a multicenter comparison of moclobemide, amitriptyline, and placebo, gastrointestinal discomfort, headache, and dizziness occurred in over 20% of moclobemide-treated patients insomnia was also common (10). In healthy volunteers there were no effects of moclobemide on psychomotor performance. Acute confusion and agitation was reported in one patient who dropped out of a clinical trial owing to this adverse effect (SEDA-16, 7). Hypomania was attributed to moclobemide in two cases (SEDA-17, 16). Aggressive behavior and mild manic symptoms were described in severely depressed patients, refractory to other treatments, who took moclobemide (SEDA-18, 15). 

There has been a systematic review of published randomized studies of the use of iV-acetylcysteine in chronic bronchitis (2). A total of 39 trials were considered, of which only nine were included in the meta-analysis. In all cases, oral A -acetylcysteine had been used in a dosage of 200-300 mg bd for 4-32 weeks. There were gastrointestinal adverse effects (dyspepsia, diarrhea, and heartburn) in 10% of 2011 patients, and 6.5% withdrew because of their symptoms. However, the rate of gastrointestinal adverse effects was higher in the placebo group (11% with a withdrawal rate of 7.1%). There was no exacerbation of chronic bronchitis in 49% of patients treated with acetylcysteine compared with 31% of placebo-treated patients, a relative benefit of 1.56 (95% Cl = 1.37, 1.77). There was also symptom improvement with treatment 61 % reported improvement in symptoms with acetylcysteine compared with 35% with placebo. 

Patoia L, Santucci L, Furno P, Dionisi MS, Dell Orso S, Romagnoli M, Sattarinia A, Marini MG. A 4-week, double-blind, parallel-group study to compare the gastrointestinal effects of meloxicam 7.5 mg, meloxicam 15 mg, piroxicam 20 mg and placebo by means of faecal blood loss, endoscopy and symptom evaluation in healthy volunteers Br J Rheumatol 1996 35(Suppl 1) 61-7. 

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