Multiple Detoxifications Research Articles

Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder.

Chronic alcohol use increases risk of alcohol withdrawal symptoms (AW) and disrupts stress biology and resilient coping, thereby promoting excessive alcohol intake. Chronic alcohol intake and multiple alcohol detoxifications are known to impair brain medial prefrontal cortex (mPFC) and striatal functioning, regions involved in regulating stress, craving and alcohol intake. In two related studies, we examined whether AW predicts this functional brain pathology and whether Prazosin versus Placebo treatment may reverse these effects. In Study 1, patients with Alcohol Use Disorder (AUD) (N = 45) with varying AW levels at treatment entry were assessed to examine AW effects on corticostriatal responses to stress, alcohol cue and neutral visual images with functional magnetic resonance imaging (fMRI). In Study 2, 23 AUD patients entering a 12-week randomised controlled trial (RCT) of Prazosin, an alpha1 adrenergic antagonist that decreased withdrawal-related alcohol intake in laboratory animals, participated in two fMRI sessions at pretreatment and also at week 9-10 of chronic treatment (Placebo: N = 13; Prazosin: N=10) to assess Prazosin treatment effects on alcohol-related cortico-striatal dysfunction. Study 1 results indicated that higher AW predicted greater disruption in brain mPFC and striatal response to stress and alcohol cues (p < 0.001, family-wise error [FWE] correction) and also subsequently greater heavy drinking days (HDD) in early treatment (p < 0.01). In Study 2, Prazosin versus Placebo treatment reversed mPFC-striatal dysfunction (p < 0.001, FWE), which in turn predicted fewer drinking days (p < 0.01) during the 12-week treatment period. These results indicate that AW is a significant predictor of alcohol-related prefrontal-striatal dysfunction, and Prazosin treatment reversed these effects that in turn contributed to improved alcohol treatment outcomes.

Effects of Multiple Detoxifications on Withdrawal Symptoms, Psychiatric Distress and Alcohol-Craving in Patients with an Alcohol Use Disorder

Previous studies have shown an association between the number of withdrawal attempts and increased severity of withdrawal symptoms in patients with an alcohol use disorder (AUD). An underlying allostatic neuroadaptive response may negatively affect the withdrawal pathology after alcohol discontinuation. The objective of the present research is to examine the intensification of psychiatric distress, craving, and post-detoxification drinking outcomes, which may result from these neurobehavioral alternations. Fifty-two AUD inpatients were divided into two groups: <2 previous detoxifications and ≥2 previous detoxifications. Patients completed the Dutch version of the Severity of Withdrawal Scale (SWS), Depression Anxiety Stress Scales (DASS-21), VAS Craving, and Desires for Alcohol Questionnaire (DAQ). Linear mixed effects models were applied, controlling for the number of drinks consumed in the past 30 days and alcohol drinking history (years). Patients who had undergone ≥2 detoxifications reported statistically significantly higher scores on SWS withdrawal and DASS psychiatric symptoms. Also, craving patterns were different between groups, as shown by a statistically significant interaction effect for VAS craving for the time of day factor (morning vs. evening). No statistically significant group differences were found for DAQ scores and post-detoxification drinking outcomes. Due to relatively low 1-month follow-up rates our power was limited to detect such a difference. The present study contributes to the existing body of evidence that multiple detoxifications are associated with aggravated withdrawal/psychiatric pathology, and distinct diurnal patterns of VAS craving. Several clinical implications are discussed and alternative strategies are provided to manage repeated cycles of detoxifications.

Illuminating a Practical Solution to Clothing Protection from Mustard Gas

Lee et al. reported the first metal-organic framework (MOF)-fiber composite for the catalytic detoxification of a mustard gas simulant. The development of such wearable catalytic materials is an important step toward developing protection equipment that can simultaneously detoxify several chemical warfare agents (CWAs) under ambient conditions.

A feasibility study of an intervention for structured preparation before detoxification in alcohol dependence: the SPADe trial protocol

BackgroundAlcohol-related harm is currently estimated to cost the National Health Service (NHS) in England £3.5 bn a year. Of the estimated 1.6 million people with some degree of alcohol dependence, some 600,000 are believed to be moderately or severely dependent and may benefit from intensive treatment. Outcomes from medically assisted withdrawal, also referred to as detoxification, are often poor, with poor engagement in relapse prevention interventions and subsequent high relapse rates. Detoxification is costly both financially and to the individual. It has been found that people who experience multiple detoxifications show more emotional and cognitive impairments. These changes may confer upon them the inability to resolve conflict and increased sensitivity to stress thus contributing to increased vulnerability risk of relapse. The study aims to test the feasibility of using a group intervention aiming to prepare participants for long-term abstinence before, rather than after, they have medically assisted detoxification. The current study will establish key parameters that influence trial design such as recruitment, compliance with the intervention, retention, and sensitivity of alternative outcome measures, in preparation for a future randomised controlled trial (RCT). This paper presents the protocol of the feasibility study.MethodsThe study corresponds to phase 2 of the Medical Research Council (MRC) complex interventions guidelines which cover the development and feasibility testing of an intervention. The work is in three stages. The development, adaptation and implementation of the Structured Preparation before Alcohol Detoxification (SPADe) intervention (stage 1), a randomised feasibility study with economic evaluation (stage 2) and a qualitative study (stage 3). Fifty participants will be recruited from two community alcohol treatment services in England. Participants will be randomised in two arms: the treatment as usual arm (TAU), which includes planned medically assisted detoxification and aftercare and the intervention arm in which participants will receive structured group preparation before detoxification in addition to TAU. The main outcomes are duration of continuous abstinence with no incidents of lapse or relapse, percentage of days abstinent and time to relapse.DiscussionThe socioeconomic harms associated with alcohol have been well-documented, yet existing treatment options have not been able to reduce high relapse rates. This study will build on existing naturalistic studies underpinned by psychological interventions offered early and before detoxification from alcohol, which aim to reverse automatised habitual behaviours and thus may help us to understand how better to support people to remain abstinent and improve post detoxification outcomes.Trial registrationISRCTN, 14621127; Registered on 22 Feb 2017

Repeated Detoxification of Alcohol-Dependent Patients Impairs Brain Mechanisms of Behavioural Control Important in Resisting Relapse

Alcohol abuse is frequently characterised by cycles of heavy drinking, detoxification, and relapse. We review evidence that multiple detoxifications are associated with impaired ability to control reward seeking, and with exaggerated responses to negative emotional stimuli. Under conditions of incentive conflict and in intra-extra dimensional shift and reversal tasks, deficits are found that are consistent with impaired executive control of behaviour by prefrontal cortical mechanisms. Correspondingly, alcoholics who have undergone multiple detoxifications show loss of grey matter in prefrontal regions associated with accurate performance of these tasks, the extent correlating with numbers of detoxifications. The ability to respond appropriately to certain emotional stimuli (e.g., fearful faces) is also impaired following multiple detoxifications. Such impairments are associated with reduced connectivity between insula and prefrontal areas but increased connectivity between insula and subcortical regions (colliculus), and between amygdala and other subcortical regions (bed nucleus of stria terminalis, BNST). Such changes may increase vulnerability to stress-induced relapse, and disrupt social abilities, contributing to social isolation.

Impairment of Cognitive Abilities and Decision Making after Chronic Use of Alcohol: The Impact of Multiple Detoxifications

In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Impact of Lifetime Alcohol Quit Attempts and Medicated Detoxifications on Time to Relapse During an Index Alcohol Detoxification

Previous work has shown that multiple medication-treated alcohol detoxifications are associated with poorer treatment outcomes during subsequent detoxifications. Little is known about the impact of nonmedicated attempts to stop drinking outside the realm of these medically supervised detoxifications on acute detoxification outcomes. This study included 58 subjects enrolled in an outpatient detoxification study. Subjects were asked why and how often they quit alcohol for 3 days or longer during their drinking lifetime using concepts derived from the Cognitive Lifetime Drinking History. The effect of previous attempts at abstinence (both medicated and nonmedicated) on time to relapse during an index detoxification was examined. After the index detoxification, older individuals relapsed later than younger individuals and the number of previous medicated detoxifications rather than total lifetime quit attempts per se was related to quicker relapse. Contrary to expectation, those who reported fewer previous nonmedicated quit attempts tended to relapse sooner than those who reported more past quit attempts. This study supports and extends previous work that suggests that the number of previous medicated detoxifications, rather than the total number of past attempts at abstinence, predicts higher and sooner risk for early relapse drinking during outpatient alcohol detoxification.

Effectiveness of daily outpatient alcohol detoxification by an Irish public psychiatric hospital - A pilot study.

To assess the effectiveness of daily outpatient alcohol detoxification in an Irish public psychiatric hospital. The outpatient records of patients presenting to the Assessment Unit of St Brendan's Hospital in one year (August 2004-July 2005) with symptoms of Alcohol Dependence Syndrome (ADS) and commencing daily outpatient detoxification were examined retrospectively for parameters relevant to the objectives of the study. The results were compiled and analysed using descriptive statistics. Forty patients underwent outpatient alcohol detoxification in one year and complete records were available for 32 patients (80%). Twenty patients had fixed addresses in the hospital catchment areas, eight patients had no fixed addresses and the remaining four patients had addresses outside the catchment areas. Seven patients (22%) presented with a co-morbid psychiatric condition including depression (four patients), anxiety disorder (two patients) and personality disorder (one patient). All seven patients were known to psychiatric sector services. Of the 32 patients commencing detoxification, 28 patients (87.5%) attended on the second day whilst 22 patients (69%) attended their third day's appointment. Only 17 patients (53%) completed the outpatient detoxification. Thirteen patients (40.6%) received at least two outpatient detoxifications during the year; of whom seven patients (58%) received their second detoxification within two months of the first one. The record of 20 patients (62.5%) showed that they had received advice regarding selfreferral to counselling services. A high proportion of patients (47%) presenting with symptoms of ADS did not complete daily outpatient detoxifications. A high proportion of all patients (40.6%) also underwent multiple outpatient detoxifications during the year. It is possible that the separation between alcohol detoxification and alcohol counselling services in Ireland contributed to these disappointing results.

Disruptions in Sleep Time and Sleep Architecture in a Mouse Model of Repeated Ethanol Withdrawal

Insomnia and other sleep difficulties are perhaps the most common and enduring symptoms reported by alcoholics undergoing detoxification, especially those alcoholics with a history of multiple detoxifications. While some studies have reported sleep disruptions in animal models after chronic ethanol exposure, the reports are inconsistent and few address sleep architecture across repeated ethanol exposures and withdrawals. The present study evaluated sleep time and architecture in a well-characterized mouse model of repeated chronic ethanol exposure and withdrawal. C57BL6/J mice were fitted with electrodes in frontal cortex, hippocampus, and nuchal muscle for collection of continuous electroencephalogram (EEG)/electromyogram (EMG) data. Baseline data were collected, after which mice received 4 cycles of 16-hour exposure to alcohol (ethanol: EtOH) vapor separated by 8-hour periods of withdrawal or similar handling in the absence of EtOH vapor. Ethanol-exposed mice attained a blood ethanol concentration of 165 mg%. Upon completion of vapor exposure, EEG/EMG data were again collected across 4 days of acute withdrawal. Data were subjected to automated analyses classifying 10-second epochs into wake, non-rapid eye movement (REM) sleep, or REM sleep states. Mice in withdrawal after chronic EtOH exposure showed profound disruptions in the total time asleep, across the acute withdrawal period. Sleep architecture, the composition of sleep, was also disrupted with a reduction in non-REM sleep concomitant with a profound increase in REM sleep. While altered sleep time and non-REM sleep loss resolved by the fourth day of withdrawal, the increase in REM sleep ("REM rebound") persisted. These results mirror those reported for the human alcoholic and demonstrate that EtOH withdrawal-induced sleep disruptions are evident in this mouse model of alcohol withdrawal-induced sensitization. This mouse model may provide mechanisms to investigate fully the high correlation between unremitting sleep problems and increased risk of relapse documented clinically.

Consequences of multiple withdrawals from alcohol.

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL, organized by Theodora Duka and chaired by Dai Stephens. The purpose of the symposium was to examine the effects of multiple experiences of withdrawal from alcohol in animals made dependent on alcohol and in humans who are alcohol dependent. Parallels were drawn to the effects of repeated short-lived high-content alcohol exposures in animals and in humans who are social drinkers but indulge in binge drinking. The presentations were (1) Multiple detoxifications and risk of relapse in abstinent alcoholics, by John Gentry and Robert Malcolm; (2) Emotional and cognitive impairments after long-term use of alcohol: relationship to multiple detoxifications and binge drinking, by Theodora Duka; (3) The effect of repeated withdrawal from ethanol on conditioning to appetitive stimuli, by Tamzin Ripley, Gilyanna Borlikova, and Dai Stephens; (4) Alcohol withdrawal kindling: electrographic measures in a murine model of behavioral seizure sensitization, by Lynn Veatch and Howard Becker; and (5) Binge drinking induced changes in CNS, by Fulton Crews.

Kindling of Withdrawal: A Study of Craving and Anxiety After Multiple Detoxifications in Alcoholic Inpatients

The increased severity of withdrawal during successive detoxifications from alcohol is well documented for seizures, but the importance of the number of withdrawal events for other withdrawal symptoms such as anxiety and for alcohol craving is not known. Studies in animals are consistent with increases in reinforcing properties of alcohol with a greater number of withdrawal experiences. Thus, we predicted that patients who had undergone multiple detoxifications would show greater desire for alcohol and might experience more anxiety compared with patients with fewer detoxifications or compared with social drinkers. Forty-two alcoholic inpatients were divided on the basis of medically supervised detoxifications into HI-med (more than two previous detoxifications, n = 6) and LO-med (two or fewer previous detoxifications, n = 36) and compared with a group of social drinkers matched for age, sex, and verbal IQ (n = 43). An additional analysis was performed by dividing the participants into HI-total (n = 22) and LO-total (n = 20) previous detoxification groups (three or more and less than three previous detoxifications, respectively) by using all previous detoxifications, which included unsupervised attempts. Anxiety was measured by Spielberger's State-Trait Anxiety Inventory; mood was evaluated by using the Profile of Mood States; craving was evaluated with a short version of the Desire for Alcohol Questionnaire; and an emotional Stroop test was used that employed positive, negative, and alcohol-related words. When the analysis was based on the medically supervised detoxifications only, alcoholic participants (HI- and LO-med) had higher ratings in trait anxiety and in feelings of anger, anxiety, depression, and confusion, but also friendliness; had higher craving ratings; and made more errors in the alcohol Stroop compared with social drinkers. In addition, the number of errors in the emotional Stroop for negative words was higher in the group with the higher number of detoxifications. When we analyzed the total number of detoxifications, this effect for the emotional Stroop errors was no longer seen. Instead, ratings of anger in the Profile of Mood States were greater in the HI-total compared with the LO-total detoxification group. These effects remained when the correlates alcohol consumption and degree of dependency were introduced as covariates, which showed that the effects found are probably attributable to the number of withdrawals. These data suggest that for inpatients with short history of alcoholism, the consequences of multiple withdrawals may not relate to anxiety or craving.

Kindling of Withdrawal: A Study of Craving and Anxiety After Multiple Detoxifications in Alcoholic Inpatients

Background: The increased severity of withdrawal during successive detoxifications from alcohol is well documented for seizures, but the importance of the number of withdrawal events for other withdrawal symptoms such as anxiety and for alcohol craving is not known. Studies in animals are consistent with increases in reinforcing properties of alcohol with a greater number of withdrawal experiences. Thus, we predicted that patients who had undergone multiple detoxifications would show greater desire for alcohol and might experience more anxiety compared with patients with fewer detoxifications or compared with social drinkers. Methods: Forty-two alcoholic inpatients were divided on the basis of medically supervised detoxifications into HI-med (more than two previous detoxifications, n= 6) and LO-med (two or fewer previous detoxifications, n= 36) and compared with a group of social drinkers matched for age, sex, and verbal IQ (n= 43). An additional analysis was performed by dividing the participants into HI-total (n= 22) and LO-total (n= 20) previous detoxification groups (three or more and less than three previous detoxifications, respectively) by using all previous detoxifications, which included unsupervised attempts. Anxiety was measured by Spielberger's State-Trait Anxiety Inventory; mood was evaluated by using the Profile of Mood States; craving was evaluated with a short version of the Desire for Alcohol Questionnaire; and an emotional Stroop test was used that employed positive, negative, and alcohol-related words. Results: When the analysis was based on the medically supervised detoxifications only, alcoholic participants (HI- and LO-med) had higher ratings in trait anxiety and in feelings of anger, anxiety, depression, and confusion, but also friendliness; had higher craving ratings; and made more errors in the alcohol Stroop compared with social drinkers. In addition, the number of errors in the emotional Stroop for negative words was higher in the group with the higher number of detoxifications. When we analyzed the total number of detoxifications, this effect for the emotional Stroop errors was no longer seen. Instead, ratings of anger in the Profile of Mood States were greater in the HI-total compared with the LO-total detoxification group. These effects remained when the correlates alcohol consumption and degree of dependency were introduced as covariates, which showed that the effects found are probably attributable to the number of withdrawals. Conclusions: These data suggest that for inpatients with short history of alcoholism, the consequences of multiple withdrawals may not relate to anxiety or craving.

The Effects of Carbamazepine and Lorazepam on Single versus Multiple Previous Alcohol Withdrawals in an Outpatient Randomized Trial

Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). A university medical center substance abuse clinic in Charleston, SC. One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Buprenorphine for opiate addiction: potential economic impact

This study evaluated the potential economic impact of the buprenorphine/naloxone combination in the context of practice in the United States of America. In comparison to treatment provided through methadone clinics, buprenorphine/naloxone therapy in office practice may be associated with increased medication, physician, and nursing costs, but reduced costs for dispensing, toxicology screens, counseling and administration. It may also result in markedly reduced costs for patients, especially travel costs, resulting in net savings for society as a whole. A review of controlled studies suggest that buprenorphine/naloxone is not likely to be any more or less effective than methadone, but since it will be less expensive in the long run, it may be more cost-effective than methadone when provided to comparable groups of patients. Because of the convenience of office-based treatment, buprenorphine/naloxone may increase access to opiate substitution for some addicts. To the extent that treatment is provided to additional high-cost patients who are involved in extensive criminal activity or who undergo multiple detoxifications each year, net cost savings could be substantial. To the extent that treatment is extended to better adjusted addicts who are employed, married and experience fewer adverse effects from their addiction, costs could increase. The total cost impact will depend on which addict sub-populations make greatest use of the treatment opportunity presented by buprenorphine/naloxone.

Multiple previous detoxifications are associated with less responsive treatment and heavier drinking during an index outpatient detoxification

Investigators have found a relationship between the number of previous alcohol withdrawals (AWs) and severity of withdrawal. We evaluated patients with multiple previous AWs, as compared to those with 0–1 previous withdrawals, in an outpatient detoxification trial comparing lorazepam (LZ) to carbamazepine (CBZ). A mixed model analysis of covariance was used to analyze Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores as a function of detoxification history (0–1 vs. 2 or more), drug group (CBZ vs. LZ), assessment day, and hours since last drink. The mixed model analysis of covariance (ANCOVA) indicated a significant detoxification history by assessment day interaction ( P≤.03). Least square means associated with this interaction suggested that the CIWA-Ar scores for the multiple detox patients declined more slowly than those with 0–1 previous detoxifications. Patients with multiple detoxes were 150% more likely to experience a heavy drinking day during treatment ( P≤.03). The multiple detox group drank more each drinking day ( P=.001) and a greater proportion of this group had early heavy drinking ( P=.0002). In the present study, intensity of AW symptoms and early heavy drinking were independent of treatment medications and were more common in patients who had previously undergone multiple treatments for AW.

Repeated Ethanol Withdrawal Delays Development of Focal Seizures in Hippocampal Kindling

Clinical studies report an increase in the prevalence of alcohol withdrawal-related seizures in patients with a history of multiple detoxifications. In order to investigate the alcohol withdrawal-related alterations in neural activity that lead to this increase in seizure propensity, basic researchers have examined both spontaneous and elicited seizures in animals undergoing withdrawal from chronic ethanol. This study was designed to further examine alcohol withdrawal-related seizure activity in a rodent model by assessing the development of electrical kindling after chronic ethanol exposure administered in multiple or single treatment episodes. Laboratory rats were exposed to either five periods of 3 days of ethanol, one 15-day period of continuous ethanol, or a period of control handling with no ethanol exposure. Ten days after a final withdrawal episode, all animals were surgically prepared with recording and stimulating electrodes. Twenty days after final withdrawal from ethanol or an equivalent period of similar handling, daily electrical stimulation of hippocampal area CA3 was initiated. Animals exposed to ethanol required more daily stimulations to become fully kindled than did ethanol-naive controls, with those animals experiencing five withdrawals requiring the most stimulations overall and more stimulations to progress from focal to generalized seizure behaviors. These results indicate that chronic ethanol exposure and withdrawal alter neuronal mechanisms important for hippocampal kindling in a manner that persists long after cessation of ethanol exposure, and they indicate that this effect is increased by exposure to repeated withdrawal episodes.

Multiple Previous Alcohol Detoxifications Are Associated With Decreased Medial Temporal and Paralimbic Function in the Postwithdrawal Period

Functional neuroimaging studies after alcohol cessation have demonstrated that chronic alcohol use globally reduces neuronal activity for several weeks. Less is known about the effects of previous alcohol use patterns on regional brain activity. Multiple previous alcohol detoxifications are associated with a worse clinical course and increased risk of seizures, perhaps due to sensitization of key brain structures. We performed the following imaging study in alcoholics in the postwithdrawal period to determine if blood flow in medial temporal structures would differ as a function of previous alcohol use (i.e., whether regions were kindled or sensitized due to multiple detoxifications). Fourteen adults meeting DSM-IV criteria for alcohol dependence (mean age 35, 8 SD; 10 men) and participating in a double-blind detoxification medication study underwent a brain perfusion Tc99 m-ECD (Neurolite) single photon emission computed tomography scan on days 7 through 9 (mean 7.6, .5 SD) after their last drink and 2 to 3 days since their last detoxification medication. Seven nonpsychiatrically ill, nonalcohol-dependent healthy adults were scanned as control subjects. Alcoholics compared with controls had widely reduced relative activity in cortical secondary association areas and relatively increased activity in the medial temporal lobes (p < 0.01). Five alcoholic patients with > or = 2 previous detoxifications were compared with five patients in their first detoxification (age and detoxification medication matched). Multiple detoxification patients had significantly lower relative activity in bilateral anterior temporal poles and medial temporal lobes and in visual cortex (p < 0.01) compared with first episode patients. These studies are consistent with other studies comparing alcoholics and controls. They also suggest that on day 7 of detoxification, alcoholic subjects with multiple previous detoxifications have decreased visual cortex, medial temporal lobes, and anterior paralimbic blood flow, compared with those in their first detoxification. Further studies seem warranted to confirm these initial exploratory results.

Multiple Previous Alcohol Detoxifications Are Associated With Decreased Medial Temporal and Paralimbic Function in the Postwithdrawal Period

Multiple Previous Alcohol Detoxifications Are Associated With Decreased Medial Temporal and Paralimbic Function in the Postwithdrawal Period

Alcohol-related seizures and the kindling effect of repeated detoxifications: the influence of cocaine.

The purpose of this study was to determine if individuals with concurrent alcohol and cocaine use differ in regard to seizure risk compared to individuals who abuse only alcohol, and to explore the relationship between multiple detoxifications and seizure risk in the context of concurrent cocaine use. In this study, alcoholic cocaine users had a decreased risk of seizure compared to alcoholics without cocaine use (P < 0.005). Seizures were rare in individuals who did not abuse alcohol. Alcoholic cocaine users reported a younger age at first seizure compared to alcoholics without cocaine use (P < 0.04). Alcoholic patients with seizures had significantly more previous detoxification experiences compared to matched alcoholic patients without seizures (P = 0.0001). Concurrent cocaine use did not appear to have an independent effect on the risk of seizure. The findings in this study suggest that concurrent cocaine use may accelerate the development of alcohol-related seizures in predisposed individuals but does not appear to substantially increase overall risk. Multiple previous detoxifications are associated with an increased risk of seizures in alcoholics both with and without concurrent cocaine use.