Subjective Adverse Effects Research Articles

1892 – Therapeutic adherence in depot medicated patients

Introduction and objectives Poor adherence remains a problem in schizophrenic patients. Treatment guidelines for schizophrenia recommend depot medications for patients who are no adherent to oral regimens. This study aims to evaluate subjective experiences, adverse effects and adherence of depot medicated patients. Methods Was applied a questionnaire composed by the “Drug Attitude Inventory” (subjectively assesses the attitude and experiences of patients towards their depot medication) and by questions about adverse effects with medications. We took into account four different depot formulations: risperidone, haloperidol, fluphenazine and zuclopenthixol. Results Participated 44 schizophrenic patients. The majority is male (77%). Clinically, the mean age of diagnosis is 28 years. About 50% of patients do the long acting risperidone, 31,8% the haloperidol decanoate and 9,1% the fluphenazine or zuclopenthixol. About 52,3% say they do not know the reason they take depot medication and 16% report previous therapeutic abandonment. There are not differences between mean results in “Drug attitude inventory” and all depot medications average in the positive range. Most frequent adverse affects are weight gain (29,5%) and sedation (15,9%). In rating discomfort of adverse affects 54,5% patients score zero (no discomfort) and 2,3% score ten (very uncomfortable) without significant differences between formulations. Discussion/conclusion Despite reporting adverse effects, patients attribute a low score in terms of discomfort. Although some of them report ignore the reason they are taking depot, patients have positive subjective experiences and attitudes with these medications. This fact may be predictive of good compliance.

Severity of anxiety and depression are related to a higher perception of adverse effects of antiepileptic drugs

After reviewing the negative effects of antiepileptic drugs (AEDs) on general health and quality of life, the Commission on Outcome Measurement from the International League Against Epilepsy (ILAE) recommended incorporating reliable and valid tools in clinical essays in order to achieve a more accurate assessment of the subjective adverse effects rate and disease severity when using AEDs. PurposeThe aim of this study was to correlate the severity of adverse effects of AEDs, with the presence of anxiety and depression in patients with epilepsy. MethodsThe Spanish version of the Liverpool Adverse Events Profile (LAEP) and the Hospital Anxiety and Depression Scale (HADS) were applied on 130 consecutive outpatients with epilepsy from the epilepsy clinic at the Mexico's National Institute of Neurology and Neurosurgery. A correlation analysis was carried out to determine if the presence of depression and anxiety was related to the adverse effects of AEDs. The relation between LAEP scores with other epidemiological variables was also assessed. ResultsOur study found a positive correlation between the LAEP and the HADS scores (p=<0.01).The most common adverse effects were drowsiness (81.5% [n=106]), difficulty in concentrating (76% [n=99]), and nervousness and/or agitation (75% [n=97]). Female gender, a history of febrile seizures, persistent seizures and polytherapy were associated with a higher toxicity on LAEP. In our study, age at epilepsy onset, duration of epilepsy, type of epilepsy and patients’ age were not related to higher LAEP scores. ConclusionAdverse effects to AEDs can be related with the presence of psychiatric disorders such as anxiety and depression in patients with epilepsy.

Linking the pharmacological content of ecstasy tablets to the subjective experiences of drug users

Most studies on the subjective effects of ecstasy are based on the assumption that the substance that was taken is 3,4-methylenedioxymethamphetamine (MDMA). However, many tablets sold as ecstasy contain other substances and MDMA in varying doses. So far, few attempts have been made to take this into account while assessing subjective effects. This study aims to link the pharmacological content of tablets sold as ecstasy to the subjective experiences reported by ecstasy users. Self-reported effects on ecstasy tablets were available from 5,786 drug users who handed in their tablets for chemical analysis at the Drug Information and Monitoring System (DIMS) in the Netherlands. Logistic regression was employed to link the pharmacological content of ecstasy tablets to the self-reported subjective effects and compare effects with MDMA to other substances present. MDMA showed a strong association with desirable subjective effects, unparalleled by any other psychoactive substance. However, the association of MDMA was dose-dependent, with higher doses (>120mg/tablet) likely to evoke more adverse effects. The novel psychostimulants mephedrone and p-fluoroamphetamine were considered relatively desirable, whereas meta-chlorophenylpiperazine (mCPP) and p-methoxymethamphetamine (PMMA) were strongly associated with adverse subjective effects. Also, 3,4-methylene-dioxyamphetamine (MDA) and benzylpiperazine (BZP) were not appreciated as replacement for MDMA. Linking the pharmacological content of ecstasy sold on the street to subjective experiences contributes to a better understanding of the wide range of subjective effects ascribed to ecstasy and provides a strong rationale for the prolonged endurance of MDMA as the key ingredient of the ecstasy market.

Variable adverse effects in subjects after ingestion of equal doses of Argyreia nervosa seeds

As the new drug Spice hit the market in 2006 and was a hot topic in the media, the general issue of legal highs has been brought to the attention of a large number of (young) people. One of these so called legal highs are the seeds of Argyreia nervosa, also known as Hawaiian Baby Woodrose, which contains the psychotropic alkaloid lysergic acid amide (LSA). A study was designed to assess how driving ability is affected by Argyreia nervosa. However, the study could not be continued due to severe adverse effects in 3 of 4 subjects, such as cardiovascular dysregulation in two and a psychosis like state in one subject. All of the participants recovered completely within 9h after ingestion. Despite body normalized doses interindividually highly differing reactions in type and intensity were observed. Furthermore, fluctuating alkaloid contents in seeds and multi-drug intoxications make the use of this legal high far more dangerous than commonly believed.

Does pharmacological dose of parenteral arginine have beneficial effect in rats with sub-acute peritonitis?

Peritonitis is a life-threatening condition that may occur as a sequela of intra-abdominal infection. The management of peritonitis includes surgical intervention, antimicrobial therapy, and nutritional support. Arginine has been reported to have beneficial and adverse effects in subjects with inflammation, which might be related to the dose, time, and route of supplementation and the disease severity. So far, the optimal doses of parenteral arginine are not known. In this study, we investigated dose effects of parenterally supplemented arginine on anabolism and arginine-derived metabolites in sub-acute inflammation. Male Wistar rats underwent modified cecal puncture procedure for induction of peritonitis were infused with total parenteral nutrition solutions for 7 days, which contained conventional, low, medium, and high doses of arginine, i.e., 1.61, 2.85, 4.08, and 6.54% of calories from arginine. Healthy, orally fed rats were included as references. On day 7, peritonitic rats had significantly decreased body weight, declined serum albumin, and increased serum nitric oxide (NO) and tumor-necrosis factor-alpha compared to references (ANOVA, P < 0.05). There were no dose effects of parenteral arginine on body weight, nitrogen retention, and serum blood urea nitrogen and creatinine in peritonitic rats. In contrast, plasma arginine, proline, and ornithine, and urinary urea nitrogen were significantly increased, whereas serum NO and plasma glutamine were significantly decreased in dose-dependent manners with parenteral arginine. Pharmacological dose of parenteral arginine may increase the synthesis of ornithine, urea, and proline instead of citrulline and NO in peritonitic rats. These results suggest that high dose of parenteral arginine may facilitate ureagenesis and proline conversion without causing augmentation of NO production in sub-acute inflammation. Therefore, pharmacological dose of parenteral arginine may not have benefits in anabolism but does not cause adverse effect in rats with sub-acute inflammation.

The subjective experience of taking antipsychotic medication: a content analysis of Internet data

We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics. We conducted a content analysis of an Internet database of comments about prescribed medications. We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety. The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits.

Efficacy study of a vest-type device for positional therapy in position dependent snorers

This study was performed to evaluate the efficacy of positional therapy using a recently developed vest-type device to treat snoring in positional-dependent snorers. Seventeen (60.7%) of the 28 subjects were diagnosed as position-dependent snorers with or without mild obstructive sleep apnea through laboratory nocturnal polysomnography and were included in a pre- and post-treatment comparative parallel study. The mean total snoring rate (from 36.7 ± 20.6% to 15.7 ± 16.2%, P < 0.0001) and snoring rate in the supine position (from 45.8 ± 22.8% to 25.4 ± 20.6%, P < 0.0001) decreased significantly with use of the vest. The mean percent change of total snoring rate between baseline and with the positional device was significant (63.5 ± 22.5%, P < 0.0001). Of the 17 subjects, 15 (88.2%) decreased their snoring rate more than 50% without subjective adverse effects. There were no significant differences in sleep efficiency, arousal index, and wake after sleep onset while sleeping with the vest-type positional device. In conclusion, positional therapy using the recently developed vest-type device is effective at decreasing snoring without subjective and objective adverse effects in position-dependent snorers with or without mild obstructive sleep apnea.

Role of Mechanical Dilatation of Cervix in Hysteroscopy

Background: Hysteroscopy with sample of the tissue is the goldstandard in the diagnosing of abnormal uterine bleeding. Operativehysteroscopy can then be performed as a therapeutic procedure inpatients presenting with intrauterine abnormalities. Cervical dilatationposes a great challenge particularly in nulligravid, post-menopausalwomen and women with cervical stenosis. Difficulties encountered indilating the cervix poses threat to complications such as cervical tears,creation of false track, hemorrhage and uterine perforation.Objective: The aim of this study is to review the role of mechanicaldilatation in hysteroscopy using oral and vaginal misoprostol andlaminaria.Methods: This study involves a retrospective analytical review andcompares the role of oral and vaginal misoprostol and laminariaapplication in achieving cervical ripening before hysteroscopy. Itseffects in cervical dilatation as well as the dosing, advantages and sideeffectswere also reviewed. There were twenty articles included in thisstudy as extracted from electronic databases Cochrane Library,Medscape, Highwire Press and Google. Most of the articles assessedthe cervical diameter by the largest number of Hegar dilators that couldbe inserted into the cervix without resistance. Subjective assessmentsof adverse effects and complications were recorded.Conclusion: Methods of cervical priming before hysteroscopy lessensthe need of further cervical dilation pre-operatively, lessens thecomplications associated with the entry of the hysteroscope into thecervical os and offered acceptable side effects.

Digest

Digest

Serum Retinol, α-Tocopherol, and β-Carotene Levels Are Not Altered by Excess Ingestion of Diacylglycerol-Containing Plant Sterol Esters

Background: Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, β-carotene, and α-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. Methods: A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. Result: There were no subjective adverse effects or changes in serum retinol, α-tocopherol, and β-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Conclusion: Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise.

市立川西病院におけるぼうこうがん患者へのＢａｃｉｌｌｕｓ Ｃａｌｍｅｔｔｅ‐Ｇｕｅｒｉｎ（ＢＣＧ）とＰｉｒａｒｕｂｉｃｉｎのぼうこう内注入療法時における自覚的副作用，１クール完遂率と注入予定回数達成率の比較

In recent years, intravesical chemotherapy has been performed for bladder cancer after transurethral resection of bladder tumors (TUR-Bt). The initial intravesical treatment with chemotherapeutic agents is performed during hospitalization, and further intravesical treatments are administered in the outpatient clinic. The intravesical agents are usually BCG (Bacillus Calmette-Guerin) which is given as a course of 8 treatments once weekly and pirarubicin which is given as a course of 10 treatments once weekly. To obtain information on subjective adverse effects for these intravesical chemotherapy regimens, a retrospective investigation comparing the subjective adverse effects per number of treatments, and the accomplishment rate and achievement rate for one course of therapy with BCG (n=9) or pirarubicin (n=21) was conducted over a two-year period using medical records and nursing records. While the accomplishment rate for pirarubicin therapy was higher than that for BCG therapy, there was no significant difference in the achievement rate between the two chemotherapy regimens. Some patients receiving BCG therapy developed fever but none on pirarubicin therapy did. Information on patients' subjective symptoms such as headache, nausea and constipation was obtained directly from the patients using an outpatient guidance sheet on which they checked the subjective adverse effects due to the intravesical chemotherapy. It seemed that the outpatient guidance sheet had made a positive contribution to the management of intravesical chemotherapy for bladder cancer.

Role of early trabeculectomy in primary open-angle glaucoma in the developing world

The lack of prospective data comparing early surgery and medical management in primary open-angle glaucoma (POAG) in the developing world led us to conduct a small randomised controlled clinical trial to evaluate acceptance and effectiveness of early trabeculectomy in these patients. A total of 60 patients with moderately advanced POAG were randomised into three groups (Group I-Conventional medical management, Group II-Option for early trabeculectomy, Group III-Received an educational package about their disease before an option for early trabeculectomy). The patients were followed up for a period of 6 months for visual acuity, intraocular pressures (IOP), and subjective satisfaction. The three study groups were statistically similar with respect to mean IOP, demographic, and socio-economic profile. 35% of the patients accepted early surgery when offered a choice between early surgery and medical management in one of the groups. 65% of patients in another group expressed willingness for an early surgery after receiving health education on glaucoma. The mean IOP in the operated eyes was lower than the medically treated eyes at 2 weeks (16.6 vs 23.0 mmHg), 6 months (18.5 vs 22.8 mmHg), and 1-year review (17.9 vs 22.3 mmHg) (P<0.001). No significant difference was seen among the groups with regard to visual acuity and subjective satisfaction. There is a reasonable acceptance of early surgery in POAG patients in the developing world and increases on educating patients about their disease. Early surgery offers better IOP control with no long-term subjective adverse effects.

Sex differences in outcome following sports-related concussion

Females comprise an increasing percentage of the athlete population across all age groups, and analysis of recent literature reveals that they sustain more concussions in collegiate sports. Results of human and animal studies indicate that females may have poorer outcomes after traumatic brain injury; however, no return-to-play guideline takes sex or other individual differences into account. In the present study the authors evaluated the influence of patient sex on objective neurocognitive performance and subjective reporting of symptoms following sports-related concussion. According to preseason baseline neurocognitive computerized testing in 2340 male and female high school and collegiate athletes, individuals who sustained sports-related concussions (155 persons) were reevaluated using an alternate form of the cognitive test. Sex differences in the magnitude of cognitive change from baseline levels and the subjective experience of symptoms were analyzed. To account for the possible protective effects of helmets, comparisons were performed among females, males with helmets, and males without helmets; none of the female athletes wore helmets. Female athletes had significantly greater declines in simple and complex reaction times relative to preseason baseline levels, and they reported more postconcussion symptoms compared with males. As a group, females were cognitively impaired approximately 1.7 times more frequently than males following concussions. Furthermore, females experienced more objective and subjective adverse effects from concussion even after adjusting for the use of helmets by some groups of male athletes (for example, in football). Return-to-play decisions and concussion management must be objective and made on an individual basis, including consideration of factors such as patient sex rather than relying on a one-size-fits-all guideline.

Subjective effects of antipsychotic treatment

Subjective effects of antipsychotic treatment

Differential response to alcohol in light and moderate female social drinkers

Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD were less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers.

Good Noise? Infrasound May Be Beneficial

Infrasound normally results in pessimistic responses, describing it as a complicated problem, bringing great misery to those exposed, whose difficulties arise from adverse subjective effects, compounded by inadequate assessment methods. But Chinese traditional medicine claims therapeutic uses for infrasound, produced from the hands of the “Qigong Masters”, using an oriental system which many in the west, nurtured in experimental science and cause-and-effect medicine, find difficult to understand, and even more difficult to accept. There have been recent changes in the UK, following a report on Complementary and Alternative Medicine (CAM) by the House of Lords Select Committee on Science and Technology.1 It was estimated that the growth of CAM in the UK results in use by about 20% of the population, with an annual expenditure in excess of £1.5 billion. A result of the report has been the acceptance that CAM has a place in the health care of the UK and that more should be available on, or at least recommended by, the National Health Service. A directory of CAM practitioners is being developed for use by NHS healthcare professionals ( www.nhsdirectory.org ).

Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials

In managing atrial fibrillation (AF), the main therapeutic strategies include rate control, termination of the arrhythmia, and the prevention of recurrences and thromboembolic events. Safety and efficacy considerations are important in optimizing the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic conversion agents. Intravenous ibutilide and oral dofetilide both have efficacies superior to placebo in controlled trials for converting persistent AF. Comparative trials in paroxysmal AF have demonstrated that flecainide, propafenone, quinidine, and sotalol are equally effective in preventing recurrences of AF. Amiodarone has been demonstrated to be more efficacious than propafenone or sotalol in the Canadian Trial of Atrial Fibrillation. In persistent AF, twice-daily dofetilide has been shown to be as or more effective than low-dose sotalol given twice daily for the maintenance of sinus rhythm in patients with AF. Trials have demonstrated that subjective adverse effects are less frequent with class IC drugs, sotalol, and dofetilide compared with such drugs as quinidine. In patients without structural heart disease, flecainide, propafenone, and d,l-sotalol are the initial drugs of choice, given their reasonable efficacy, low incidence of subjective side effects, and lack of significant end-organ toxicity. Treating AF in patients with left ventricular dysfunction can be difficult because of associated electrophysiologic derangements, potential proarrhythmic concerns, and negative inotropic effects of antiarrhythmics. Some data exist suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can prevent AF either by preventing atrial dilation and stretch-induced arrhythmias or by blocking the renin-angiotensin system. In post–myocardial infarction patients, d,l-sotalol, dofetilide, and amiodarone—and in congestive heart failure patients, amiodarone and dofetilide—have demonstrated neutral effects on survival in controlled trials. In the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), amiodarone lowered the frequency of AF development and improved left ventricular ejection fraction over time. In CHF-STAT, there was lower mortality in patients who converted from AF to sinus rhythm. Dofetilide decreased rehospitalization for congestive heart failure in the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trials. Neutral effects on survival and favorable hemodynamics have positioned amiodarone and dofetilide as the antiarrhythmics of choice in patients with left ventricular dysfunction. In post–myocardial infarction patients, sotalol is an additional agent to consider for treatment of AF in this setting.

Effect of 6-month adherence to a very low carbohydrate diet program

Purpose To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic parameters. Subjects and methods Fifty-one overweight or obese healthy volunteers who wanted to lose weight were placed on a very low carbohydrate diet (<25 g/d), with no limit on caloric intake. They also received nutritional supplementation and recommendations about exercise, and attended group meetings at a research clinic. The outcomes were body weight, body mass index, percentage of body fat (estimated by skinfold thickness), serum chemistry and lipid values, 24-hour urine measurements, and subjective adverse effects. Results Forty-one (80%) of the 51 subjects attended visits through 6 months. In these subjects, the mean (± SD) body weight decreased 10.3% ± 5.9% ( P <0.001) from baseline to 6 months (body weight reduction of 9.0 ± 5.3 kg and body mass index reduction of 3.2 ± 1.9 kg/m 2). The mean percentage of body weight that was fat decreased 2.9% ± 3.2% from baseline to 6 months ( P <0.001). The mean serum bicarbonate level decreased 2 ± 2.4 mmol/L ( P <0.001) and blood urea nitrogen level increased 2 ± 4 mg/dL ( P <0.001). Serum total cholesterol level decreased 11 ± 26 mg/dL ( P = 0.006), low-density lipoprotein cholesterol level decreased 10 ± 25 mg/dL ( P = 0.01), triglyceride level decreased 56 ± 45 mg/dL ( P <0.001), high-density lipoprotein (HDL) cholesterol level increased 10 ± 8 mg/dL ( P <0.001), and the cholesterol/HDL cholesterol ratio decreased 0.9 ± 0.6 units ( P <0.001). There were no serious adverse effects, but the possibility of adverse effects in the 10 subjects who did not adhere to the program cannot be eliminated. Conclusion A very low carbohydrate diet program led to sustained weight loss during a 6-month period. Further controlled research is warranted.

Multiple drug rescue therapy for HIV-infected individuals with prior virologic failure to multiple regimens.

To characterize the antiviral response and tolerability of a multi-drug rescue therapy (MDRT) among heavily pretreated patients. Observational study conducted in a single, university-based tertiary referral clinic. Patients (n = 106) who failed several prior regimens started MDRT including at least five antiretroviral (ARV) drugs between August 1997 and June 1998. The most common starting regimen included three nucleoside reverse transcriptase inhibitors and two protease inhibitors, which was prescribed to 45 (42.5%) patients. Virologic response was defined as plasma viral load < 400 copies/ml on at least two consecutive visits. Median prior ARV exposure was seven drugs over a median time of 43 months. Fifty-nine percent of the patients were phenotypically (VIRCO Antivirogram) resistant at baseline to seven or more ARV. Median plasma viral load change following initiation of MDRT was -1.04 log10 copies/ml over a median of 15 months. Using intention-to-treat analysis 40% of patients had plasma viral load values < 400 copies/ml between weeks 47 and 57 of follow-up. Twenty-six patients (25%) experienced severe laboratory abnormalities or subjective adverse drug effects and six of these participants discontinued therapy. MDRT induced a substantial antiviral response in this heavily pretreated group of patients despite extensive phenotypic resistance at baseline. Adverse effects were frequent but generally manageable. Our data suggest that relying exclusively on historical, clinical and laboratory evidence may not be sufficient to rule out a possible antiviral response when multiple drug regimens are used in this heavily pretreated patient population.

A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults

ObjectiveThe purpose of this study was to determine the effects of 3-acetyl-7-oxo-dehydroepiandrosterone (7-oxo-DHEA) in healthy overweight adults. MethodsIn a double-blind, placebo-controlled protocol, 30 adults (28 women and 2 men; mean age, 44.5 ± 11.5 years) with a mean body mass index of 31.9 ± 6.2 kg/m2 were randomly divided into 2 groups of 15: Group 1 received 7-oxo-DHEA 100 mg twice daily and Group 2 received placebo for 8 weeks. All subjects participated in an exercise training program 3 times per week. Each exercise session consisted of 60 minutes of cross-training (aerobic and anaerobic exercise) under the supervision of an exercise physiologist. In addition, each subject was instructed to follow a diet of ~1800 kcal/d (20 kcal/[kg · d]) by a registered dietitian. Subjects received biweekly dietary counseling to encourage compliance. Study participants underwent serum multiple-assay chemistry testing, as well as body composition, blood pressure, and dietary analysis at baseline, week 4, and week 8. ResultsOf the 30 subjects who entered the study, 23 completed the 8-week protocol. Seven subjects dropped out for personal reasons unrelated to the study. Group 1 lost a significant amount of body weight compared with Group 2 (ȡ2.88 kg vs ȡ0.97 kg; P = 0.01) over the 8 weeks. Group 1 also achieved a significant reduction in body fat compared with Group 2 (ȡ1.8% vs ȡ0.57%; P = 0.02). The rate of change in body fat per 4-week interval in Group 1 was 3.1 times that in Group 2 (ȡ0.88% vs ȡ0.28%; P< 0.01). Group 1 also experienced a significant increase in triiodothyronine (T3) levels compared with Group 2 over the 8-week study period (+17.88 ng/dL vs 2.75 ng/dL; P = 0.04). There were no significant changes in levels of thyroid-stimulating hormone (TSH) or thyroxine (T4) in either group. In addition, no significant changes were observed in vital signs, blood sugar, testosterone and estradiol levels, liver and renal function, or overall caloric intake during the study. No subjective adverse effects were reported throughout the study. ConclusionsThe results of the study suggest that 7-oxo-DHEA combined with moderate exercise and a reduced-calorie diet significantly reduces body weight and body fat compared with exercise and a reduced-calorie diet alone. In addition, 7-oxo-DHEA significantly elevated T3 levels but did not affect TSH or T4 levels, indicating that it does not adversely affect thyroid function in the short term.