Placebo abnormalities

In a particularly dramatic case of placebo-induced side effects, doctors at a hospital in Jackson, Mississippi, treated a young man who came into the emergency room, said to the receptionist, Help me, I took all my pills and then collapsed to the floor, dropping an empty prescription container. His blood pressure was abnormally low, and he was treated with intravenous fluids, which brought it back to within a normal range. The prescription bottle bore a label indicating that the medication was part of a clinical trial of antidepressants. Further investigation revealed that he had... 

A randomized placebo-controlled trial found that 39% of the tamoxifen-treated women had an endometrial abnormality, a percentage that was reduced to 10% of women on placebo (p < 0.0001) (Kedar et al. 1994), though no cases of endometrial cancer were diagnosed in this study. The histological abnormalities found in the tamoxifen group were atypical hyperplasia (16%), proliferative endometrium (13%), polyps (8%), or presence of mitosis (2%). The authors concluded that the predicative value of an endometrium thickness... 

Studies using calcium channel blockers in the treatment of BPAD began in the late 1970s and early 1980s when it was suspected that abnormalities of calcium activity inside nerve cells might contribute to the brain dysfunction of BPAD. Unfortunately, all of the double-blind placebo controlled studies of calcium channel blockers in the treatment of BPAD have failed to demonstrate their efficacy. 

Anticonvulsdnts. An early observation that BN patients may have abnormal electroencephalogram (EEG) resnlts led to specnlation that binge eating may represent an atypical behavioral presentation of seiznre activity. Thus, the first controlled medication study for the treatment of BN evaluated the use of the antiseizure medication phenytoin (Dilantin). Phenytoin was not found to be significantly superior to placebo, and the earlier reports of EEG abnormalities were not confirmed. The results of a subsequent trial of carbamazepine (Tegretol), an anticonvulsant that has been reported to be effective in the treatment of bipolar disorder, were also disappointing. As a result, anticonvulsants are not routinely used in the treatment of BN. 

Coordination difficulties - A total of 3.4% of levetiracetam-treated patients experienced coordination difficulties (reported as either ataxia, abnormal gait, or incoordination) vs 1.6% with placebo. 

Lab test abnormalities Elevations of liver enzymes and CPK, lymphopenia, and neutropenia occurred. These were reported in similar proportions of zanamivir and lactose-vehicle placebo recipients with acute influenza-like illness. 

The most frequent adverse events and abnormal laboratory values reported in the placebo-controlled clinical trial of oral zidovudine were granulocytopenia and anemia. 

Lapierre YD, Browne M, Horn E, et al Treatment of major affective disorder with fluvoxamine. J Clin Psychiatry 48 65-68, 1987 Lapierre YD, Ravindran AV, Bakish D Dysthymia and serotonin. Int Clin Psychopharmacol 8 (suppl 2) 87-90, 1993 Lapin 1, Oxenkrug G Intensification of the central serotonergic process as a possible determinant of thymoleptic effect. Lancet 1 132-136, 1969 Larkin JG, McKee PJ, Blacklaw J, et al Nimodipine in refractory epilepsy a placebo-controlled, add-on study. Epilepsy Res 9 71-77, 1991 Larsson LI, Rehfeld JF Localization and molecular heterogeneity of cholecystokinin in the central and peripheral nervous system. Brain Res 165 201-218, 1979 Laruelle M, Abi-Dargham A, Casanova M, et al Selective abnormality of prefrontal serotonergic receptors in schizophrenia a post mortem study. Arch Gen Psychiatry 50 810-818, 1993... 

In one double-blind, randomized, placebo-controlled study, patients were given a daily dose of 40 or 120 mg ziprasidone or placebo for 28 days in 132 patients ( 136). There was a statistically significant improvement in psychotic symptoms versus placebo in the 120 mg/day ziprasidone group as measured by the total BPRS and the CGI scores. Evaluations for parkinsonian symptoms, akathisia, abnormal movements, and sedation did not reveal any notable treatment effects. No significant differences existed between drug and placebo in the total number of adverse events, laboratory test abnormalities, or more serious adverse events. Thus, this study documented that 60 mg ziprasidone twice daily was an effective strategy with negligible risks. 

Galantamine (Razadyne) [Cholinesterase Inhibitor] Uses Alzheimer Dz Action Acetylcholinesterase inhibitor Dose 4 mg PO bid, T to 8 mg bid after 4 wk may T to 12 mg bid in 4 wk Caution [B, ] T Effect w/ suc-cinylcholine, amiodarone, dildazem, verapamil, NSAIDs, digoxin X- effect w/ anticholinergics, T risk of death vs placebo Contra Severe renal/hepadc impair Disp Tabs, soln SE GI disturbances, wt loss, sleep disturbances, dizziness, HA Interactions T Effects W/ amitriptyline, cimeddine, erythromycin, fluoxetine, fluvoxamine, ketoconazole, paroxetine, quinidine EMS Use succinylcholine w/ caudon, may need a reduced dose monitor ECG for induced conduction abnormalities OD May cause cholinergic Sxs (SLUDGE), muscle weakness, resp depression, and Szs atropine may be used as antidote... 

During one 3-year study, under 1% of 596 women taking placebo or an estrogen + a progestogen had an abnormal endometrial biopsy. Of women taking an unopposed estrogen, 12% developed typical hyperplasia, 23% complex hyperplasia, and 28% simple hyperplasia. Use of HRT for 15 or more years resulted in a significantly... 

Powles TJ, Bourne T, Athanasiou S, Chang J, Grubock K, Ashley S, Oakes L, Tidy A, Davey J, Viggers J, Humphries S, Collins W. The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo. Br J Cancer 1998 78(2) 272-5. 

In a 56-week study there was an association between the dose of acarbose in the range 50-300 mg tds and the development of abnormal liver function in 359 patients with type 1 (21%) and type 2 diabetes (38). The patients took the maximum tolerated dose, and 30% took doses of 100 mg or less. Of the patents who were randomized to acarbose (n = 240), 8% developed abnormal liver function tests (alanine transaminase activity more than three times the upper limit of normal) compared with 1% of those who took placebo (n — 119). The dose of acarbose was 200-300 mg tds in those who developed abnormal liver function. Liver function recovered promptly on withdrawal. 

In a multicenter, double-blind, randomized, fixed-dose trial of placebo and repaglinide 1 mg and 4 mg for 24 weeks in 361 patients there were no episodes of severe hypoglycemia (28). Most patients withdrew from the placebo group because of hyperglycemia, hypoglycemia, erythematous rash, headache, diarrhea, fatigue, or abnormal vision. Adverse effects had about the same frequencies in the two groups. 

M.W. Konstan. 2001. A two-year randomized, placebo-controlled trial of dor-nase-a in young patients with cystic fibrosis with mild lung function abnormalities./. Pediatr. 139 813-820. 

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