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Biomedical subjects

Markus Gastpar

Publications and source records attributed to Markus Gastpar.

26 records · Page 2Linked to original sources
PubMed2003

Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.

A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.

Acetates↗
PubMed2002

Sympathetic neural activation evoked by mu-receptor blockade in patients addicted to opioids is abolished by intravenous clonidine.

BACKGROUND: Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification. METHODS: Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration. RESULTS: Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P < 0.001) and catecholamine plasma concentrations (P < 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change. CONCLUSIONS: Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.

Adrenergic alpha-Agonists↗
PubMed2002

Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study.

In a placebo-controlled, double-blind German multicenter study (seven sites) the efficacy of naltrexone as an adjunctive treatment in alcoholism to maintain abstinence was assessed for 12 weeks. A total of 171 detoxified patients (97.7% met the DSM-III-R criteria for alcohol dependence) were included. Patients had been abstinent for a mean of 19.5 +/- 9.4 days at study entry. Eighty-four and 87 patients were randomized to receive naltrexone (50 mg/day) and placebo, respectively. Each site was instructed to provide its usual psychosocial alcohol treatment program. The primary effectiveness measure was the time to first heavy drinking as derived from self-reports of drinking (timeline-follow-back method). Secondary effectiveness measures included time to first drink, amount of alcohol consumption, intensity of craving, severity of alcoholism problems, and liver enzymes. Thirty-three (38%) placebo patients and 28 (33%) naltrexone patients discontinued the study. At endpoint, 62% of the patients in each group did not have an episode of heavy drinking. Also, there were no significant differences between the study groups concerning secondary effectiveness measures as well as compliance and adverse clinical events--with the exception of the gamma-GT, which was significantly greater reduced in the naltrexone group throughout the study. Based upon an intention-to-treat population, this study confirms the safety but not the efficacy of naltrexone in prevention of alcohol relapse. Nevertheless, the question arises whether self-reports of drinking are more reliable than gamma-GT as a measure of recent alcohol consumption.

Adult↗
PubMed2002

Chronic mu-opioid receptor stimulation alters cardiovascular regulation in humans: differential effects on muscle sympathetic and heart rate responses to arterial hypotension.

In opioid addicted patients, respiratory regulation adapts allowing intake of otherwise lethal dosages of opioids. In contrast, little is known about cardiovascular regulation during chronic opioid receptor stimulation. We previously demonstrated that chronic mu-opioid receptor stimulation by methadone decreases resting muscle sympathetic activity (MSA). However, for short-term control of arterial blood pressure autonomic responses to arterial hypotension may be of greater importance. Accordingly, we tested the hypothesis that chronic opioid receptor stimulation attenuates muscle sympathetic and heart rate responses to arterial hypotension. Ten young patients (mean +/- SD, 30 years +/- 6) with a long history of mono-opioid addiction and under oral methadone substitution therapy (54 mg d(-1) +/- 31) for 12 months (+/-20) were studied. Peroneal MSA (microneurography) and heart rate responses to hypotensive challenges (sodium nitroprusside) were assessed in the awake state and compared with those of 10 matched healthy subjects. Effects of mu-opioid receptor blockade by naloxone (12.4 mg i.v.) were determined during propofol anesthesia. Chronic mu-opioid receptor stimulation markedly decreased the MSA response to hypotension (-0.5 units mm Hg(-1) +/- 0.2 vs. -2.0 +/- 1.8; p = 0.01) compared with healthy subjects despite similar arterial blood pressure and heart rate at rest. In contrast, the heart rate response to hypotension did not differ between addicted patients (6 ms mm Hg(-1) +/- 2) and healthy subjects (7 ms mm Hg(-1) +/-4). Opioid receptor blockade during propofol anesthesia markedly increased the MSA response to hypotension even beyond awake values (-1.2 units mm Hg(-1) +/- 1.1; p = 0.02 vs. awake) while the heart rate response remained unchanged. Thus, chronic mu-opioid receptor stimulation 1) results in uncompensated depression of cardiovascular sympathetic neural regulation, and 2) exerts differential effects on efferent sympathetic nerve activity to muscle and on heart rate control in response to arterial hypotension.

Adult↗
PubMed2002

Concomitant endocrine and immune alterations during alcohol intoxication and acute withdrawal in alcohol-dependent subjects.

Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers.

Alcoholic Intoxication↗
PubMed2002

Partial response and nonresponse to antidepressant therapy: current approaches and treatment options.

BACKGROUND: Response to antidepressant drug therapy is less than optimal for a considerable proportion of depressed patients; at present, however, few data exist to guide their rational therapeutic management. This review describes general principles for the management of such patients. This review is the result of an expert roundtable meeting convened to review published clinical data and clinical experience and provide clinicians with evidence-based principles on the management of patients who fail to respond optimally to initial antidepressant therapy. ROUNDTABLE FINDINGS: Failure to respond may be defined as a < 25% decrease on an accepted symptom rating scale such as the Montgomery-Asberg Depression Rating Scale (MADRS) or the Hamilton Rating Scale for Depression (HAM-D) in a patient who has received an adequate dosage for 4 weeks. In these patients, a neuropharmacologic rationale exists to switch to an agent with a different mode of action or a dual action. Partial response may be defined as 6 to 8 weeks at an adequate dosage and 25% to 50% decrease in MADRS or HAM-D score. In these patients, dose escalation should be considered, followed by augmentation and switching strategies. For augmentation, knowledge of neuropharmacology may allow prediction of which second agent will potentiate or complement the action of the first agent; it may also permit the prediction of potential safety concerns. CONCLUSIONS OF THE PANEL: On the basis of a review of the medical literature and clinical experience regarding patients with partial response or nonresponse to antidepressant drug therapy, it appears that simultaneous targeting of both the noradrenergic and serotonergic systems is one of the most effective augmentation strategies. Switching to an agent of a different class is probably optimal for those patients who fail to respond to first-line therapy.

Antidepressive Agents↗
PubMed2002

[Acute treatment of opiate addiction in patients in 2001].

The acute treatment of opiate addiction includes a broad variety of divers treatment strategies that depend on the different degrees of institutionalisation, the levels of access to treatment and on various treatment strategies such as substitution, psychosocial support and specific psychotherapies. The present report reflects part of the intermediate state of discussion within the group of specialists that is developing guidelines for the acute treatment of opiate addicts. Readers are invited to comment prior to the publication of the definitive text of the guidelines.

Germany↗