Dexamethasone suppression test in recently detoxified alcoholics: clinical implications

An overnight dexamethasone suppression test (DST) was performed on 66 nondepressed primary alcoholics, a mean of 20.79 +/- 11.5 days after last alcohol intake. The Beck Depression Inventory (BDI) was given concurrently. Only 6% of the subjects were nonsuppressors. There was no correlation between cortisol levels at 17 and 24 hours postdexamethasone and the age of the subjects or duration of abstinence. There was a low level correlation between cortisol values at 24 hours and the BDI scores. Review of published data indicates that the DST may be abnormal in alcoholics in the first 2 weeks of abstinence, probably a result of abnormal liver function and withdrawal phenomena. DST response of alcoholics resembles that of normal controls after more than 2 weeks of abstinence. Alcoholics with clinical features of depression and an abnormal DST after 2 weeks of abstinence may be candidates for antidepressant therapy or electroconvulsive therapy.     

The relationship between depression and the dexamethasone suppression test following alcohol withdrawal in a psychiatric population

The authors administered at least one dexamethasone suppression test (DST) and Hamilton Rating Scale for Depression (HRSD) simultaneously to 30 psychiatric inpatients following detoxification from alcohol. Twenty-five of these were also interviewed using the NIMH Diagnostic Interview Schedule (DIS). Fifteen patients had two or three sequential DSTs at weekly intervals. Seven of the patients were clinically diagnosed as having a major depressive episode based on close observation over 2 to 4 inpatient weeks free of psychotropic medications. Fifty-eight percent of the initial cortisol determinations with the first 2 weeks showed nonsuppression, as did 60% after 2 weeks. While the level of depressive symptoms was initially high (HRSD score greater than 20) for 48% of the 27 patients interviewed within 2 weeks of abstinence, depressive symptoms cleared within 2 weeks in half of these cases. There were no associations between DST results and the presence of DSM-III major depressive disorder (lifetime or current) as assessed by the NIMH DIS, scores on the HRSD, or the presence of liver disease (elevated admission SGOT or SGPT). By the 15th-day of abstinence an examination of the clinical course of depressive symptoms differentiated those patients with a persistent major depressive episode from those with transient, alcohol-related depressive symptoms. An early positive DST had a positive predictive value of 20% for a clinical diagnosis of a major depressive episode, and a negative predictive value of 73%. After 2 weeks the positive and negative predictive values were each 50%.     

The role of cognitive structure in college student problem drinking

Although motivational models of alcohol use often invoke constructs relevant to affective distress (e.g., depressive symptoms), to date, no study has assessed the potential role of cognitive structures (enduring cognitive belief systems) in promoting problematic drinking behavior. Thus, the current study evaluated the relationship between cognitive structure, specifically dysfunctional attitudes and automatic negative thoughts, and problem-related drinking, while controlling for the influence of alcohol consumption, drinking motives related to affect management, demographic variables, and depressive symptoms. Participants were 182 male and female (80%) college undergraduates, who completed a battery of self-report questionnaires on two occasions, separated by 8 weeks. Initial correlational analyses indicated strong (positive) associations among the cognitive structure variables, depressive symptoms, and problem drinking behavior. Findings from set-wise hierarchical regression analyses demonstrated that dysfunctional attitudes measured at Time 1 (T1) predicted problem drinking eight weeks later at Time 2 (T2) even after controlling for age and sex, alcohol consumption (T2), depressive symptoms (T2), and drinking motives linked to affect regulation (T1). These findings highlight the potential importance of cognitive structure as a risk factor for problem drinking, above and beyond the risk posed by more traditionally studied variables.     

A retrospective chart review comparing tiagabine and benzodiazepines for the treatment of alcohol withdrawal

Although benzodiazepines are the standard of care in the treatment of alcohol withdrawal, several studies have suggested that anticonvulsants may be equally effective at alleviating alcohol withdrawal symptoms and may pose less of a risk of causing rebound of symptoms which could contribute to relapse. This report compares treatment outcomes for patients (N=13) treated for alcohol withdrawal with either the anticonvulsant tiagabine or the benzodiazepines oxazepam and lorazepam. The Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) was utilized to gauge alcohol withdrawal symptoms over the course of the study. When possible, follow-up data was obtained on alcohol use post-treatment. Both benzodiazepines and tiagabine appeared to reduce CIWA-Ar scores at about the same magnitude. There was a trend for tiagabine patients to have less post-detoxification drinking (Fisher exact test, p = 0.12). The reduction in alcohol withdrawal symptoms and decreased tendency to relapse observed in patients treated with the anticonvulsant tiagabine suggests that a double-blind, placebo controlled trial may be warranted.     

Types of alcohol withdrawal syndrome and dexamethasone suppression test

Several data show a biological heterogeneity of the alcohol withdrawal syndrome. The determination of basic cortisol level and the Dexamethasone Suppression Test (DST) were performed in 10 healthy men and 54 male alcoholics in the stage of acute withdrawal divided into four groups, according to their clinical symptoms. In 46% of the patients the DST was positive (vs. nil in controls). The positive DST was significantly higher in subjects where depressive symptoms especially of endogenous character prevailed. The cortisol level was significantly increased in subjects characterized predominantly by anxiety-irritation. The possible explanations of these findings are discussed. The clinical picture of the withdrawal syndrome may be determined by disturbed functions of the hypothalamo-pituitary-adrenal system (HPAS). Correction of such disorders seems to be sufficient when treating acute withdrawal syndromes of different types.     

Is long-term heavy alcohol consumption toxic for brain serotonergic neurons? Relationship between years of excessive alcohol consumption and serotonergic neurotransmission.

The relationship between years of excessive alcohol consumption and central serotonergic neurotransmission, as assessed by the prolactin (PRL) response to D-fenfluramine, was investigated in 22 male alcohol-dependent subjects. A negative correlation was obtained, that is, the longer duration of excessive alcohol consumption the lower PRL response to D-fenfluramine. It is therefore suggested that long duration of excessive alcohol consumption in alcohol-dependent subjects causes a reduction in central serotonergic neurotransmission, possibly by a toxic effect of alcohol on serotonin neurons. The relationship between depressive and anxiety symptoms during on-going drinking and the PRL response to D-fenfluramine was also investigated. No such correlations were obtained, suggesting that reduction in central serotonergic neurotransmission does not pre-dispose to the development of depressive and anxiety symptoms, at least in relation to on-going drinking in alcohol-dependent subjects.     

Excessive ethanol drinking following a history of dependence: animal model of allostasis.

Alcohol withdrawal symptoms, particularly negative emotional states, can persist for months following the removal of alcohol. These protracted withdrawal symptoms have been implicated as an important trigger of relapse to excessive drinking in alcoholics and may represent a long lasting shift in affective tone as a result of chronic alcohol exposure. It was shown previously that ethanol-dependent rats increased their operant responding for ethanol when tested during the first 12 hr after withdrawal. The purpose of the present experiments was to determine the persistence of this finding by examining operant oral ethanol self-administration in rats with a history of physical dependence upon ethanol, detoxified and then allowed a two week period of protracted abstinence. The results of these experiments indicate that operant responding for ethanol was enhanced during protracted abstinence by 30-100% and remained elevated for 4-8 weeks post acute withdrawal. These results have important implications for understanding the characteristics and mechanisms underlying vulnerability to relapse.     

Sertraline treatment of co-occurring alcohol dependence and major depression

BACKGROUND: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders. METHOD: Following a 1-week, single-blind, placebo lead-in period, 328 patients with co-occurring major depressive disorder and alcohol dependence were randomly assigned to receive 10 weeks of treatment with sertraline (at a maximum dose of 200 mg/d) or matching placebo. Randomization was stratified, based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking, resulting in a sample of 189 patients with Hamilton Depression Rating Scale scores > or =17 (group A) and 139 patients with Hamilton Depression Rating Scale scores < or =16 (group B). RESULTS: Both depressive symptoms and alcohol consumption decreased substantially over time in both groups. There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients. CONCLUSION: Despite careful attention to methodological considerations, this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence. The high rate of response among placebo-treated patients may help to explain these findings. Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders.     

慢性酒中毒所致精神障碍的临床特征及综合式家庭治疗的远期疗效对照

目的:分析慢性酒中毒所致精神障碍的临床特征,探索综合式家庭干预对远期戒酒的疗效。方法:对231例符合ICD-10中使用酒精所致精神障碍患者的临床资料进行回顾性分析,并将其中的163例依入组先后分为干预组(82例)和对照组(81例),干预组进行综合式家庭干预。结果:231例慢性酒中毒所致精神障碍患者中妄想症占29.4%、急性醉酒状态占25.1%、戒断综合征占24.6%及肝功异常占55.0%。干预组和对照组在再住院、完全或基本戒酒、社会功能与饮酒有关的负性事件(违法行为、离异和失业等)等多个方面差异有显著性(P<0.01)。结论:慢性酒中毒所致精神障碍患者的临床特征以戒断综合征、急性醉酒和妄想等为主,主要的躯体损害为肝功异常。对慢性酒中毒所致精神障碍患者而言,综合式家庭干预是维持疗效的较好方法。     

Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y systems: implications for the development of alcoholism

Alcoholism is a chronic relapsing disorder, accompanied by alterations in psychological and physiological functioning, which reaches an addictive state where an individual demonstrates uncontrollable compulsive alcohol drinking and impairment in social and occupational functioning. Withdrawal is one of the defining characteristics of dependence, characterized by impaired physiological function and enhanced negative affect, and is thought to be a major contributing factor to relapse. The negative emotional aspects of withdrawal appear to be more involved in continued alcohol craving because physical withdrawal symptoms are not highly correlated with relapse in alcoholics. Allostasis describes maintaining stability outside the homeostatic range by varying the internal milieu to match environmental demands. This concept has been applied to neurobiological models of drug addiction and is thought to contribute to the vulnerability of drug addicts to relapse, as addicts continue to use drugs in order to maintain their psychological state within a homeostatic range. With regard to alcohol, two neuropeptides appear to be involved in the regulation of alcohol-related stress, corticotropin-releasing factor (CRF), which is associated with an increased stress response and negative affect, and neuropeptide Y (NPY), a neuropeptide with anxiolytic properties. The hypothesis to be developed in the present review is that a dysregulation of the CRF and NPY systems significantly contributes to the motivational basis of continued alcohol-seeking behavior during alcohol dependence. It appears that increases in CRF contribute to the negative affective state that is strongly associated with alcohol withdrawal, and NPY provides a motivational basis to consume alcohol because the anxiolytic effects of alcohol, which are strongly associated with relapse, appear to be regulated in part by this neuropeptide.     

Clinical efficacy of paroxetine in resistant depression

The antidepressant effects of a specific reuptake inhibitor of 5-hydroxytryptamine (5-HT), paroxetine, were tested in 24 patients with resistant depression who had failed to respond to conventional antidepressants after at least 4 weeks of treatment. A novel exper imental design was chosen in which all patients had 12 weeks of treatment beginning and ending with placebo therapy with 6 weeks of active drug treatment at some point in between. Ratings of depressive symptoms were made using the Hamilton rating scale (HRS) for depression, and the checklist for unwanted effects and their severity was also recorded before and during treatment at 2 week intervals. The change from placebo to active paroxetine therapy was made using a double-blind procedure. Patients who made a significant placebo response in the first 2 weeks of treatment were excluded from further analysis; 20 patients completed the study and satisfied all criteria for inclusion. Both groups of showed a significant improvement in symptoms after 4 weeks of paroxetine therapy. There were no significant treatment differences between the groups, but improvement in symptoms occurred sig nificantly later in the patients who had a longer period of initial placebo therapy. The experimental design also allowed study of withdrawal effects after stopping active treatment. There was no increase in adverse effects, including a subgroup associated with withdrawal problems, either during treatment with paroxetine or after the drug was stopped. The results suggest that paroxetine is probably an effective antidepressant, is well tolerated and has few adverse effects.     

Kindling in alcohol withdrawal

In many alcoholics, the severity of withdrawal symptoms increases after repeated withdrawal episodes. This exacerbation may be attributable to a kindling process. Kindling is a phenomenon in which a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly. Both clinical and experimental evidence support the existence of a kindling mechanism during alcohol withdrawal. Withdrawal symptoms, such as seizures, result from neurochemical imbalances in the brain of alcoholics who suddenly reduce or cease alcohol consumption. These imbalances may be exacerbated after repeated withdrawal experiences. The existence of kindling during withdrawal suggests that even patients experiencing mild withdrawal should be treated aggressively to prevent the increase in severity of subsequent withdrawal episodes. Kindling also may contribute to a patient's relapse risk and to alcohol-related brain damage and cognitive impairment.     

Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse

Rationale Research has demonstrated that psychosocial stressors increase smoking and risk for smoking relapse. Alterations in biological systems involved in the stress response caused by chronic smoking may contribute to early relapse. Objectives We examined the extent to which pituitary–adrenocortical and cardiovascular responses to stress following the first 24 h of a quit attempt predict early relapse. Methods Seventy-two smokers interested in cessation attended a laboratory stress session 24 h after the beginning of their cessation attempt. Adrenocorticotropin (ACTH), plasma and salivary cortisol concentrations, systolic and diastolic blood pressure (BP), and heart rate (HR) responses to acute psychological stressors (public speaking and cognitive challenges) were used to predict relapse over a 4-week follow-up period. Results Those who relapsed within 4 weeks showed attenuated hormonal and cardiovascular responses to stress and exaggerated withdrawal symptoms. Cox proportional hazards survival analysis showed that attenuated ACTH, plasma cortisol, systolic and diastolic BP, positive affect, and exaggerated withdrawal symptoms and smoking urges during acute stress predicted early relapse. Stepwise model showed that ACTH, diastolic BP, and exaggerated withdrawal symptoms remain as significant predictors. When baseline smoking and psychological measures were included in the model, changes in ACTH, diastolic BP, and both factors of smoking urges remained significant predictors of relapse. Conclusions These results demonstrate that altered stress response predicts increased vulnerability for smoking relapse.     

Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal

Levels of endorphins were determined in CSF from alcoholics while intoxicated or after 1 day, 1 week, and 3 weeks of abstinence, respectively, and from healthy volunteers. The level of endorphins was determined by a radioreceptor assay and two fractions were analyzed. With fraction 1, there were no significant differences between the groups, but the level was negatively correlated with the blood-alcohol level. The mean level of endorphin fraction 2 during the early withdrawal phase was significantly lower than those of the other groups. With respect to clinical conditions and monoamine metabolites, fraction 2 in early withdrawal correlated significantly to duration of abuse and age. During late withdrawal, fraction 1 level correlated to depressive symptoms and, after 3 weeks of abstinence, fraction 2 correlated to MOPEG levels. This study suggests that endorphin systems are affected during alcohol intoxication and withdrawal in alcoholics.     

Personality pathology,depression and HPA axis functioning

Hypothalamic pituitary adrenal (HPA) axis functioning, as measured by the dexamethasone suppression test (DST), has been extensively investigated in major depressive disorder (MDD). Evaluating DST response in MDD patients while simultaneously considering clinically relevant personality disorders may further clarify the contribution of both personality pathology and HPA axis function to depressive symptoms. The present study measured personality pathology by administering the revised version of the Millon Clinical Multiaxial Inventory (MCMI-II) in a sample of 25 patients diagnosed with MDD. Analyses revealed that suppressors (n = 19) scored significantly higher than non-suppressors (n = 6) on six of the 13 MCMI-II personality disorder scales: Avoidant, Schizoid, Self-Defeating, Passive-Aggressive, Schizotypal and Borderline. Increased personality pathology was associated with normal suppression of cortisol following the DST. This suggests that suppression of the DST may be associated with depressive states linked with personality pathology while the more biologically based depression is associated with abnormal HPA pathophysiology. Copyright 2001 John Wiley & Sons, Ltd.     

Is gender relevant only for problem alcohol behaviors? An examination of correlates of alcohol use among college students

This study examined correlates of alcohol use: substance-use coping, drinking to "feel high," and depressive symptoms as related to drinking behaviors in males and females. A sample of 266 female and 140 male college students from a private and public college were surveyed. Males reported more frequent alcohol use, alcohol-related problems, binge drinking, substance-use coping, and drinking to "feel high." There were no gender differences in self-reported depressive symptoms. Alcohol-use frequency and binge drinking were both accounted for by substance-use coping and drinking to "feel high" among males and females. However, alcohol-related problems were accounted for by males' frequency of alcohol use and drinking to "feel high," whereas females' problems were accounted for by frequency of alcohol use and depressive symptoms. Findings indicate that motivation for drinking is a more robust correlate of alcohol-related problems among males, while depressive symptomatology is a more relevant correlate of alcohol-related problems among females.     

Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder

Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up.     

The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status

Fifty consecutively admitted male alcoholics (mean age = 42.8 +/- 8.5 years) were selected. This study shows objectively that 31/50 chronic alcoholics (62%) were found to be severely depressed (Hamilton Depression Rating Scale (HRS) greater than 22); 12/50 (24%) moderately depressed (HRS = 16-22); and 7/50 (14%) were not depressed (HRS less than 15). According to dexamethasone suppression test (DST) results, 8 out of 50 patients showed escape from suppression with 2 mg dexamethasone while 42/50 showed normal suppression. Depression in alcoholics may be of neurotic type or it may be ethanol-induced reactive depression. Raised cortisol levels and abnormal DST response showed a definite tendency towards normalisation after total abstinence accompanied by clinical improvement of depressive symptomatology. The DST showed improvement on improvement of mood and sleep in these patients during total abstinence. An abnormal DST response in chronic alcoholics seems to be state-related and not trait-dependent; it seems to be a non-specific test for depression in alcoholics. Hepatic status was affected equally in both suppressors and non-suppressors of DST. It is therefore suggested that abnormal DST in alcoholics may be due to the abnormality of the hypothalamo-pituitary-adrenocortical (HPA) axis and not due to abnormal hepatic function or histological status.     

Subsensitive alpha-2-adrenoceptor function in male alcohol-dependent individuals during 6 months of abstinence

Postsynaptic alpha-2-receptor function, as assessed by growth hormone (GH) response to clonidine (CLON), has been shown to be downregulated in patients investigated in acute but also in late withdrawal after heavy alcohol intake. The results are however sometimes conflicting. The question whether this changed receptor function is a trait or state marker is not fully investigated so far. A total of seven male patients with alcohol dependence according to DSM-IV were assessed for the postsynaptic alpha-2-receptor function with the CLON/GH test (2.0 microg/kg body weight; i.v.) starting immediately after a period of heavy drinking. Neuroendocrine tests were repeated after 7 days, 2 and 6 months. A total of six healthy males were used as controls. The maximum GH responses to CLON were significantly lower on all four test occasions in the patient group as compared to the controls. Furthermore, in the patient group all neuroendocrine test results showed blunted GH responses to CLON. Thus, patients with downregulated alpha-2-receptor function during acute withdrawal after heavy alcohol intake showed similar subsensitive receptor function abnormality after a prolonged period of abstinence. The findings in this study indicate that alcohol dependent individuals have a persistent subsensitive alpha-2-adrenoceptor function which may constitute a trait factor for alcohol dependence.