Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcohol consumption has been shown to be associated with abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in humans. However, conflicting data exist in the literature, with particular regard to studies performed in actively drinking or withdrawn alcoholics; in addition, the frequent presence of depressive disturbances in such patients may importantly affect the neuroendocrine findings. In this study, we investigated HPA function in 12 male alcoholics, in whom the presence of depression and other possible confounding factors was excluded, during the first and second weeks after cessation of ethanol intake. The plasma corticotropin (adrenocorticotropic hormone, ACTH) and cortisol levels in response to both a stimulation test with human corticotrophin-releasing hormone (CRH; 100 micrograms IV) and an insulin (0.15 UI/kg IV)-induced hypoglycaemia (ITT) were measured; the cortisol response to a standard overnight dexamethasone (1 mg) suppression test (DST) was also tested. While the mean baseline ACTH and cortisol levels, measured in the morning (0800-0830 h), were not different from those of controls, ACTH and cortisol responses to the CRH test were markedly reduced (area of secretion p < .01 and p < .05, compared to controls). Similarly, the patient group showed an almost absent ACTH and cortisol release following insulin infusion (area of secretion p < .01 compared to controls, in either case). In four patients, non-suppression of plasma cortisol levels was seen on the DST, but no significant difference from normal suppressors was noted as far as the clinical features were concerned. These findings suggest that impaired hypothalamic and pituitary responsiveness, unrelated to depressive disturbances, occurs in recently withdrawn chronic alcoholics. While the possible influence of the alcohol withdrawal syndrome should be taken into account, such a pattern may be due to increased activity of the HPA axis, even in the face of preserved basal adrenal secretion. Whether these findings reflect a direct effect of sustained ethanol exposure on the components of the HPA axis, or a non-specific marker of impaired adaptation in chronic alcoholics, deserves further investigation.
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PMID:An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics. 881 25

Significant progress has been made in the pharmacotherapy of alcoholism, specifically in the areas of withdrawal reaction, decreasing consumption, relapse prevention, and comorbid psychiatric illnesses. Psychosocial interventions are an important component of treatment strategies, and studies into the efficacy of medications often include psychotherapy or other nonpharmacological modalities. Increasingly, however, the evidence reveals the effectiveness of drug treatments for various components of the illness. Many different pharmacological agents and dosage regimens have been investigated for the treatment of the alcohol withdrawal syndrome. The effectiveness and simplicity of giving long-acting benzodiazepines, using a loading-dose technique, make this regimen first-line therapy. Both naltrexone (an opioid antagonist) and acamprosate (calcium acetylhomotaurinate) increase rates of abstinence and decrease relapse rates in alcohol-dependent individuals who are in abstinence-orientated programmes. If patients enter a comprehensive treatment programme, either naltrexone or acamprosate should be considered as an option in the treatment plan. The choice of medication is most likely to be determined by the availability of each, which differs considerably throughout the world. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) seem to have short term effects, and are more effective in depressed alcoholics-dependent and in men. For all medications there is wide variability in treatment response (i.e. effect size) and compliance seems to be essential for successful treatment. Preliminary evidence suggests the usefulness of pharmacotherapy in treating alcohol dependence in the presence of other comorbid psychiatric illnesses. Antidepressants have shown efficacy in the treatment of alcoholism with comorbid depression, as has buspirone for the treatment of comorbid chronic anxiety symptoms. Further understanding of the neurobiological mechanisms of dependence in animals and humans as well as improved knowledge of predictors of treatment response will lead to improvements in the pharmacotherapy of alcohol dependence.
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PMID:Recommended drug treatment strategies for the alcoholic patient. 980 4

Gamma hydroxybutyric acid, a central inhibitory neurotransmitter and a cerebral metabolite of gamma-aminobutyric acid, is present in high concentrations in the mammalian hypothalamus and basal ganglia. Its sodium salt gamma hydroxybutyrate has been effectively used as an intravenous anaesthetic agent, and as an oral sedative, and in the management of the alcohol withdrawal syndrome. In an animal model, using 72 Wistar strain rats allocated to one of six groups of 12 animals each, with implanted lumbar intrathecal catheters, we examined whether gamma hydroxybutyrate, 20% 40 microL (32 mg kg-1) administered alone or combined with fentanyl, gamma hydroxybutyrate 20% 20 microL (16 mg kg-1), fentanyl 0.005% 20 microL (4 mg kg-1) as an intrathecal bolus, provides intraoperative anaesthesia, comparable with that produced by intrathecal lignocaine. We demonstrated that gamma hydroxybutyrate, given by an intrathecal bolus in the rat model, produced reversible segmental antinociception, together with muscular relaxation of the abdominal wall and rear limbs. This is accompanied by moderate sedation without haemodynamic or respiratory depression. This agent may thus be promising for use as a spinal anaesthetic drug.
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PMID:Spinal anaesthesia with gamma hydroxybutyrate. A study in a rat model. 1039 Jun 69

Gamma-Hydroxybutyrate (GHB) has been shown to mimic different central actions of ethanol, to suppress alcohol withdrawal syndrome, and to reduce alcohol consumption both in rats and in humans. The aim of the present study was to determine if GHB shared with alcohol the ability to inhibit glutamate action at both NMDA and AMPA/kainate receptors. The NMDA or the AMPA/kainate receptors-mediated postsynaptic potentials were evoked in CA1 pyramidal neurons by stimulation of Schaffer-collateral commissural fibers in the presence of CGP 35348, bicuculline to block the GABA(B) and GABA(A) receptors, and 10 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX) or 30 microM DL-2-amino-5-phosphonovalerate (d-APV) to block AMPA/kainate or NMDA receptors, respectively. GHB (600 microM) produced a depression of both NMDA and AMPA/kainate receptors-mediated excitatory postsynaptic potentials with recovery on washout. The GHB receptors antagonist, NCS-382, at the concentration of 500 microM had no effect per se on these responses but prevented the depressant effect of GHB (600 microM) on the NMDA and AMPA/kainate-mediated responses. In the paired-pulse experiments, GHB (600 microM) depressed the amplitude of the first and the second evoked AMPA/kainate excitatory postsynaptic potentials, and significantly increased the paired-pulse facilitation (PPF). These results suggest that GHB inhibits excitatory synaptic transmission at Schaffer-collateral commissural-pyramidal neurons synapses by decreasing the probability of release of glutamate.
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PMID:Gamma-Hydroxybutyrate inhibits excitatory postsynaptic potentials in rat hippocampal slices. 1051 69

The death of a 36-year-old alcoholic man who died after developing seizure activity while being treated with tramadol, as well as with venlafaxine, trazodone, and quetiapine, all of which interact with the neurotransmitter serotonin, is reported. The decedent, who had a history of chronic back pain, alcoholism, depression, mild hypertensive cardiovascular disease, and gastritis, had just been discharged from the hospital after 4 days of alcohol detoxification treatment. During the admission, no withdrawal seizures were noted. The morning after discharge, a witness observed the decedent exhibiting seizure activity and then collapsing. An autopsy was performed approximately 6 hours after death, and the anatomic findings were consistent with seizure activity and collapse, which included biting injuries of the tongue and soft-tissue injuries of the face. Toxicologic analysis identified tramadol, venlafaxine, promethazine, and acetaminophen in the urine; tramadol (0.70 mg/L) and venlafaxine (0.30 mg/L) in the heart blood, and 0.10 mg of tramadol in 40 ml of submitted stomach contents. No metabolites, such as acetate, acetone, lactate, and pyruvate, were found in the specimens that would be characteristically found in a person with alcohol withdrawal syndrome. The threshold for seizures is lowered by tramadol. In addition, the risk for seizure is enhanced by the concomitant use of tramadol with selective serotonin reuptake inhibitors or neuroleptics, and its use in patients with a recognized risk for seizures, i.e., alcohol withdrawal. The cause of death in this individual was seizure activity complicating therapy for back pain, depression, and alcohol withdrawal syndrome. The data in Adverse Event Reporting System of the Food and Drug Administration from November 1, 1997 to September 8, 1999 was reviewed along with a MEDLINE search from 1966 to the present. This case appears to be the first reported death caused by seizure activity in a patient taking tramadol in combination with drugs that affect serotonin.
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PMID:Lethal combination of tramadol and multiple drugs affecting serotonin. 1111

This paper analyzes the variation of suicide by day of the week in alcohol dependence, with public holidays taken into consideration. From 1949 through 1969, 1,312 patients with alcohol dependence were admitted to the Department of Psychiatry in Lund. By 1997, a total of 102 (99 men) alcoholic patients had taken their own life. Suicide victims with severe depression and other diagnoses were compared. There was a suicide peak on the first two days after weekends and holidays in patients with alcohol dependence (p < .05). Alcohol withdrawal is proposed as a contributor to the suicide peak.
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PMID:A suicide peak after weekends and holidays in patients with alcohol dependence. 1288 19

Although relatively little attention has been paid to the question how acute alcohol withdrawal might affect cognitive functions, this factor remains of particular interest because it influences psychotherapeutic treatment during detoxification. The clinical outcome and neuropsychological state of 37 inpatients with alcohol withdrawal was investigated in a randomized single-blind approach. Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared. Among comparable groups (related to gender, age, initial alcohol level, severity of abuses, severity of initial withdrawal symptoms such as tremor, perspiration, psychomotor agitation, hallucinations, orientation, intelligence, patient demographics), CBZ is just as potent as CMZ in therapy of withdrawal symptoms (circulatory function, vegetative function, psychomotor activity). Patients in both groups showed initial impairments in some neuropsychological tests (d2, Zahlen-Verbundings test, Beck Depression Inventory, Anxiety Sensitivity Index) with significant improvement during detoxification. Additionally, CBZ-treated patients showed significantly better verbal memory performance during the first days of treatment. Without any addictive potential, CBZ therapy could be very supportive in alcohol detoxification. In addition a higher verbal memory performance state could be favourable for a psychotherapeutic approach.
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PMID:Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance--a pilot study. 1520 38

The most frequently used agents for treatment of alcohol withdrawal syndrome are benzodiazepines and clomethiazole. Both have the main disadvantage of potential misuse and respiratory depression. Therefore their use in patients with respiratory diseases is limited. In recent years a treatment strategy with combined carbamazepine and tiapride was reported to be an effective alternative in alcohol withdrawal without the risk of respiratory depression. We report the successful treatment with carbamazepine and tiapride of a patient with probable sleep apnoe syndrome and history of withdrawal-related epileptic seizures.
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PMID:Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride in a patient with probable sleep apnoe syndrome. 1574 34

Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was first introduced in clinical anaesthesic practice more than 40 years ago. The drug was nearly forced from clinical practice because of its prolonged and variable duration of action. The results of recent clinical studies indicate a re-evaluation of GHB in various clinical fields. In the intensive care unit, GHB may be a favourable alternative to established drugs. The results of various clinical studies also suggest that GHB is efficacious in the treatment of alcohol withdrawal syndrome, and narcolepsy. GHB has been used successfully for short-term sedation in children. In addition, GHB has emerged as a street drug ("liquid ecstasy"). Overdose may lead to respiratory depression, coma, and even death. Chronic abuse itself may lead to severe withdrawal syndrome. The purpose of this article is to outline the neurophysiological, pharmacodynamic and pharmacokinetic characteristics of GHB, and to summarize the potential fields of use and misuse of GHB in clinical medicine and toxicology.
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PMID:[Gamma-hydroxy butyric acid: neurotransmitter, sedative and party drug]. 1609 38

Alcohol dependence increases the risk of associated psychiatric disorders. The most common disorders are depression, anxiety and personality disorders. Depression is usually secondary to alcohol dependence. It is often associated with an increased risk of suicidal behavior. The best suited treatment for an association between alcohol dependence and depression is alcohol withdrawal. Antidepressant treatment should only be initiated after at least two weeks of complete withdrawal. Alcohol withdrawal is also suggested for the association between anxiety and alcoholism. Some forms of anxiety, such as social phobia, are particularly often associated with alcoholism, since alcohol is often used for its anxiolytic and disinhibition effects.
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PMID:[Alcohol dependence and abuse and psychiatric disorders]. 1683 3


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