[Pharmacological treatment of alcohol dependence. Acamprosate and naltrexone offer new approach].
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Acamprosate↗
Biomedical subjects
J Balldin
Publications and source records attributed to J Balldin.
Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.
In 163 patients with dementia disorders, subdivided into Alzheimer's disease with early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56), vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22) the dexamethasone suppression test (DST) was performed. The patients were rated according to the DSM-III-R criteria as having mild, moderate or severe dementia and were also assessed using the GBS scale which gives a profile of the dementia syndrome. In the total group of dementia there were significant correlations between severity of dementia and post-DST levels. The frequency of pathological DST also correlated significantly with the severity of dementia. In the subgroups of dementia a strong correlation between severity of dementia and high post-DST cortisol levels was found only in the VAD group. Between the subgroups of dementia disorders there were no significant differences in basal cortisol levels. The percentage of pathological DST was lowest in the AD group (40%). It was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%) and highest in the NUD group (59%). When the relationship between post-DST cortisol levels and GBS scores was analyzed, significant correlations were found mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and restlessness correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in a substantial number of demented patients. In VAD and to a certain extent also in SDAT a disconnection between cortical areas, including the hippocampus, and the hypothalamus is assumed. Overactivity in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an insufficient feedback system leads to chronic stress adaptation failure.
Aged↗
Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake.
In an open study, 14 alcohol-dependent male patients were treated with the selective serotonin reuptake inhibitor (SSRI) Zimelidine, 200 mg daily, for six months. They were given psychosocial therapy before and during the study. The number of days of alcohol intake was statistically significantly reduced from a mean of 14 days per month before to 1-5 days during drug treatment. No effect was observed on the amount of daily alcohol intake on drinking days. No tolerance to the effect of Zimelidine was observed during the study. The findings suggest an effect of combined psychosocial support with SSRI treatment that seems to be of clinical significance.
Adult↗
Neuroendocrine evidence for reduced serotonergic neurotransmission during heavy drinking.
A fenfluramine (60-mg oral dose) challenge test was performed in 19 male heavy drinkers (mean daily consumption 88 g of pure alcohol). Twelve healthy males served as controls. The prolactin and temperature responses to fenfluramine were significantly reduced in the group of heavy drinkers. The results suggest impaired central serotonergic neurotransmission in alcoholism, possibly involving subsensitivity in various serotonin receptor subtypes.
Adult↗
Effect of citalopram on alcohol intake in heavy drinkers.
The effect of the selective serotonin reuptake inhibitor citalopram (40 mg daily dose) on alcohol intake was investigated in a double-blind, placebo-controlled cross-over study. Thirty men with heavy alcohol consumption (mean daily alcohol intake 111 +/- 51 g pure alcohol) completed the study. After a 2-week baseline period, subjects were randomly allocated to treatment with either citalopram or placebo for 5 weeks. In the total sample of heavy drinkers, no difference was found between citalopram and placebo treatment in alcohol consumption or days of abstinence. However, the response to citalopram was negatively correlated (rs = -0.67, p < 0.01) with baseline levels of mean daily alcohol intake. Therefore, we divided the total sample into two subgroups with baseline mean daily alcohol intake above and below median (107 g pure alcohol), respectively. In the group with the higher baseline values (138 +/- 25 g pure alcohol), citalopram was not different from placebo in reducing the daily alcohol intake, but in subjects with the lower baseline values (85 +/- 15 g pure alcohol), citalopram was significantly (p < 0.01) superior to placebo. Consequently, citalopram at the present dose appears capable of reducing alcohol intake only in a subgroup of heavy drinkers with a mean daily consumption of between 60 and 100 g pure alcohol.
Adult↗
Alcoholics with reduced dopamine D2 receptor function possess normal platelet monoamine oxidase activity.
Platelet monoamine oxidase (MAO) activity, proposed to be a marker for central 5-hydroxytryptamine (5-HT) capacity, was investigated in 14 severely alcohol-dependent subjects with reduced dopamine (DA) D2 receptor function, as assessed by the growth hormone responses to apomorphine. Twelve healthy men were used as controls. Platelet MAO activity in the alcohol-dependent subjects was not different from that in controls. The finding from this preliminary study suggests that severely alcohol-dependent subjects with reduced DA D2 receptor function have normal 5-HT capacity.
Adult↗
Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium.
The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.
Adult↗
Hypothalamic dysfunction in dementia.
In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.
Aged↗
Guanfacine as an alpha-2-agonist inducer of growth hormone secretion--a comparison with clonidine.
Doses of 0.5 mg and 1.0 mg of the alpha-2-adrenoceptor agonist guanfacine (GUA) and NaCl were administered intravenously (IV) in a randomized order to 18 healthy male subjects. GUA induced growth hormone (GH) secretion in a dose-dependent manner without affecting blood pressure or heart rate or inducing sedation. The effects of GUA 1.5 mg i.v. was compared with those of another alpha-2-adrenoceptor agonist, clonidine (CLON) 150 micrograms i.v. in six other male volunteers. Both alpha-2-agonists increased GH to similar levels. CLON reduced both systolic and diastolic blood pressure levels, whereas GUA reduced only systolic levels. Sedation was significantly more pronounced after CLON. The results suggest that the GUA/GH-test (1.5 mg GUA i.v.) may be an alternative to the CLON/GH-test in neuroendocrine assessment of alpha-2-adrenoceptor sensitivity.
Adrenergic alpha-Agonists↗
Further neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholism.
D2 dopamine receptor function, as assessed by growth hormone (GH) responses to apomorphine (APO; 0.18-0.24 mg i.v.), was investigated in 15 male alcoholics with reported long-term abstinence. Results from only nine subjects could be evaluated. These subjects had been heavy alcohol consumers for a mean of 15 +/- 10 years and had thereafter been abstinent for a mean of 7 +/- 6 years prior to the investigation. Eight male healthy subjects, all of whom were light social drinkers, were selected as controls. The maximum GH responses to APO were significantly lower in the alcoholics (5.8 +/- 5.8 mU/l) than in the controls (22.1 +/- 19.2 mU/l). This finding gives neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholics with long-term abstinence.
Adult↗
[Five points for better treatment of alcoholics in health care services].
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Alcoholism↗
Alpha-2-adrenoceptor sensitivity in early alcohol withdrawal.
Growth hormone (GH), blood pressure, and pulse rate responses to clonidine (100 micrograms IV) were studied three times during the first week of alcohol withdrawal in 19 alcohol-dependent patients. Fifteen healthy men were used as controls. The results suggest reduced sensitivity of the alpha-2-adrenoceptors involved in GH secretion for at least 1 week after the end of alcohol intake. In contrast, very short-lasting subsensitivity was found in the alpha-2-adrenoceptors regulating blood pressure.
Adult↗
Neuroendocrine evidence for decreased function of alpha 2-adrenergic receptor after electroconvulsive therapy.
Growth hormone (GH) and hypotensive responses to clonidine (150 micrograms, i.v.) were investigated before and after electroconvulsive therapy (ECT) in 16 depressed patients. Because of high baseline serum GH concentrations, results from only 10 patients could be evaluated. The level of GH secretion induced by clonidine was significantly reduced after ECT, but the hypotensive responses to clonidine remained unchanged. The results indicate downward regulation of the sensitivity of alpha 2-adrenergic receptors in the hypothalamus after ECT.
Blood Glucose↗
Dexamethasone suppression test in alcohol withdrawal: relationship to depression and liver function.
The relationship between dexamethasone suppression test (DST) response, depressive symptoms and liver function tests was investigated in 15 male alcohol-dependent patients for 2 weeks during alcohol withdrawal. Six of the patients relapsed into drinking within the investigation period. There was no association between DST response and relapse, which suggests that abnormal DST response has no predictive value for relapse into drinking. About 50% of the patients had abnormal DST responses during the first week of alcohol withdrawal. There was no relationship between DST response and depression or depressive symptoms. Depression remitted within 1-2 weeks, whereas DST responses remained abnormal for at least 2 weeks in 2 of the non-relapsing 9 patients. Abnormal DST response in alcohol withdrawal is unlikely to be due to alterations in liver function but may be attributable to the effect of alcohol on the hypothalamic-pituitary-adrenocortical axis.
Adult↗
A rating scale for assessment of alcohol withdrawal psychopathology (AWIP).
For patients in alcohol withdrawal, there are several scales designed to assess physiological disturbances, but there seems to be a lack of scales for assessment of psychopathology. To develop and evaluate a rating scale for psychopathology, items from the Comprehensive Psychopathological Rating Scale (CPRS) were selected, and patients meeting the DSMR-III-R criteria for alcohol dependence (303.90) were rated on these items. The patients were divided into two groups according to the length of time passed since their last period of alcohol consumption. The groups are referred to as the group (n = 53) in early withdrawal, rated daily during 1 week and the group (n = 13) in late withdrawal, rated once a week for 7 weeks. To justify inclusion in the new scale, items had to either indicate psychopathology in at least half of the patients in one of the groups in withdrawal, or be sensitive to changes over time at a 0.1% level of significance. Seventeen items fulfilled one of these criteria. The scale was tested for inter-rater reliability in a new sample of patients (n = 30) in early withdrawal. Inter-rater reliability, as well as internal consistency, was found satisfactory. This new scale, capable of identifying psychopathology and changes over time, may be used alone or together with physiological scales to identify subgroups of patients undergoing withdrawal.
Alcohol Withdrawal Delirium↗
Erythema multiforme caused by lithium.
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Erythema Multiforme↗
Individual mood profiles in alcohol withdrawal.
Daily self-reports of moods, using a Swedish Mood Adjective Check List with six bipolar dimensions, were performed in patients with alcohol dependence. One group (n = 13), consisting of inpatients in late withdrawal at a home for addicts, was studied for 6 weeks; another group (n = 12), consisting of outpatients in full remission, was studied for 1 week. The results of the ratings on the check-list were used to test a statistical model for its capacity to describe the individual courses of mood states during the recovery process. Time Series Analysis revealed that the individual courses of moods fitted an autoregressive statistical model and could thereby be summarized in numerical measures for individual baselines, amplitudes, and lengths of recovery. Such individual profiles of the alcohol recovery process, may be useful for both clinical and research purposes, making it possible, for instance, to predict points in time for an individual's recovery with respect to his total well-being, as well as the various dimensions of his mood states.
Adult↗
Alcohol withdrawal and mood.
The usefulness of a self-report technique for description of mood was tested at various stages of alcohol withdrawal. The Mood Adjective Check List (MACL), consisting of 71 mood-associated adjectives and measuring 6 bipolar aspects of mood, was used. Three groups of alcohol-dependent patients (DSM-III-R) reported on their momentary mood states twice a day, respectively, during early withdrawal (n = 78), during late withdrawal (n = 13), and after full remission (n = 12). Significant improvement was found in all 6 mood dimensions during early withdrawal. Improvement in 3 basic mood dimensions was also found during late withdrawal, thus indicating a prolonged time of recovery. The reports given by patients in full remission showed no changes in mood over time. Relative to norm group values, significant differences were found in 4 of the 6 mood dimensions for patients in very early withdrawal. The present study shows that mood changes attributable to after-effects of alcohol intake can be assessed and described during various stages of withdrawal.
Adult↗