Carrie L. Randall

GENDER DIFFERENCES IN SUBSTANCE USE DISORDERS

Despite the fact that the rate of substance abuse and dependence is higher among men than it is among women, the prevalence rates, especially the more recent ones, indicate that a diagnosis of substance abuse is not gender specific. From the emerging literature on gender differences over the past 25 years, male and female substance abusers are clearly not the same. Women typically begin using substances later than do men, are strongly influenced by spouses or boyfriends to use, report different reasons for maintaining the use of the substances, and enter treatment earlier in the course of their illnesses than do men. Importantly, women also have a significantly higher prevalence of comorbid psychiatric disorders, such as depression and anxiety, than do men, and these disorders typically predate the onset of substance-abuse problems. For women, substances such as alcohol may be used to self-medicate mood disturbances, whereas for men, this may not be true. Although these comorbid disorders might complicate treatment for women, women are, in fact, responsive to treatment and do as well as men in follow-up. Gender differences and similarities have significant treatment implications. This is especially true for the telescoping phenomenon, in which the window for intervention between progressive landmarks is shorter for women than for men. This is also true for the gender differences in physical and sexual abuse, as well as other psychiatric comorbidity that is evident in female substance abusers seeking treatment. The barriers to treatment for women are being addressed in many treatment settings to encourage more women to enter treatment, and family and couples therapy are standard therapeutic interventions. Negative consequences associated with substance abuse are different for men and women, and gender-sensitive rating instruments must be used to measure not only the severity of the problem but also to evaluate treatment efficacy. To determine whether gender differences observed over the past 25 years become less demarcated in comparisons of younger cohorts of substance abusers in the future will be interesting. Changing societal roles and attitudes toward women, the increase in women entering the workplace, in general, and into previously male-dominated sports and professions, in particular, may influence not only opportunities to drink but also drinking culture. Some gender differences likely will remain, but other gender differences will probably also emerge. The comparison of male and female substance abusers promises to be a fruitful one for researchers. The translation if the research findings to the treatment community to improve treatment outcome for both sexes will be an equally exciting challenge for the field.

Self-medication in social phobia: A review of the alcohol literature☆

It is well documented that many individuals endorse the belief that alcohol reduces social anxiety. Individuals with social phobia, therefore, might be expected to use alcohol as a coping strategy in an attempt at self-medication. The purpose of the present paper was to review the published literature on the relationship between alcohol use and social phobia to test the self-medication hypothesis (SMH). Support for one aspect of the SMH was found; individuals with social phobia use alcohol to reduce anxiety. Support for the second premise, that alcohol actually reduces social anxiety, was less conclusive.

Drinking to Cope in Socially Anxious Individuals: A Controlled Study

BACKGROUND Several hypotheses exist to account for the higher than normal rate of alcoholism in individuals with high trait anxiety (or anxiety disorders). Most of these suggest that the practice of drinking alcohol to reduce anxiety leads to an increased risk of alcoholism in vulnerable individuals. The first assumption of the hypothesis is that anxious individuals use alcohol to cope with their anxiety. Few studies have examined this issue systematically, and none have used a nonanxious matched control group. METHODS Twenty-three individuals with high social anxiety and 23 nonsocially anxious matched controls were included in the study. Groups were similar on demographic variables and alcohol use. All participants were queried regarding the use of alcohol to cope, the practice of avoiding social situations if alcohol was not available, and the degree of relief attained by alcohol. Participants also were asked about using alcohol in 11 specific situations. RESULTS The socially anxious group was significantly more likely than controls to report using alcohol to feel more comfortable in social situations and to avoid social situations if alcohol was unavailable. They also reported a greater degree of relief of anxiety from alcohol. Exploratory analyses revealed that socially anxious individuals reported using alcohol more to cope with social interactions than with social performance situations. CONCLUSIONS Individuals high in social anxiety deliberately drink alcohol to cope with their social fears. They report that alcohol is moderately effective at reducing their anxiety, which is seemingly sufficient to allow them to endure social situations. The data support the first assumption of the self-medication hypothesis-that alcohol is used to reduce social discomfort in socially anxious individuals; however, the study was not designed to address the veracity of the self-medication hypothesis as a whole. Results can help guide future studies that examine the relationship between social anxiety and alcohol.

Teratogenic actions of ethanol in the mouse: A minireview

The deleterious effects of prenatal ethanol exposure have been extensively documented in clinical and experimental studies. This paper provides an overview of work conducted with mice to examine the myriad of adverse consequences that result from embryonic/fetal exposure to ethanol. All of the hallmark features of the clinical fetal alcohol syndrome have been demonstrated in mice, including prenatal and postnatal growth retardation, structural malformations and behavioral abnormalities associated with central nervous system dysfunction. As expected, the severity and profile of effects is related to both dosage level and timing of exposure. In addition, these effects have been demonstrated following acute and chronic exposure, with a variety of routes of administration employed. Furthermore, a number of strains have been used in these studies and the variant response (susceptibility) to the teratogenic actions of ethanol exhibited among different mouse strains support the notion that genetic factors govern, at least in part, vulnerability to these effects of ethanol. More recent studies using mouse models have focused on examining potential mechanisms underlying the full spectrum of ethanols teratogenic actions.

Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder

BACKGROUND Posttraumatic stress disorder (PTSD) frequently co-occurs with alcohol use disorders. This study investigated the use of sertraline, a serotonin reuptake inhibitor, in treating co-occurring symptoms of alcohol dependence and PTSD. METHODS A total of 94 individuals with current alcohol dependence and PTSD were randomly assigned to receive sertraline (150 mg/day) or placebo for 12 weeks. Post hoc cluster analysis of baseline characteristics was used to define subgroups of participants. RESULTS There was a significant decrease in alcohol use during the trial in both the sertraline and the placebo groups. Cluster analysis revealed significant medication group by cluster interactions for alcohol-related outcomes. Sertraline-treated participants with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day (p < 0.001). For participants with more severe alcohol dependence and later onset PTSD, the placebo group had significantly greater decreases in drinks per drinking day (p < 0.01) and average number of drinks consumed per day (p < 0.05). CONCLUSIONS There may be subtypes of alcohol-dependent individuals who respond differently to serotonin reuptake inhibitor treatment. Further investigation of differential responders may lead to improvements in the pharmacological treatment of co-occurring alcohol dependence and PTSD.

A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.

INTRODUCTION Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. METHODS One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratings > or =10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels. RESULTS CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. CONCLUSIONS Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

Acute alcohol intoxication, mood states and alcohol metabolism in women and men.

The course of alcohol absorption and elimination was investigated in seven women and nine men administered a moderate (0.66 ml/kg) dose of 95% ethanol. Women were tested during the postmenstrual phase (Day 6-7), when levels of estrogen and progesterone were estimated to be relatively low. Data reflecting alterations in physical sensations, perceived levels of intoxication, and positive and negative mood states were also collected. Women reached significantly higher peak blood alcohol concentrations (BACs) than men (p less than 0.01). However, differences in peak BACs between men and women could be explained by differences in body water content between the sexes. When the raw data on BACs were corrected for differences in body water content between men and women, no difference in the amount of alcohol metabolized, or in the length of time necessary to metabolize that amount of alcohol, could be found between the sexes. Although women attained higher blood and, presumably, brain levels of ethanol, men did not differ from women in perceived levels of intoxication, physical sensations and mood states. Acute alcohol intoxication appeared to elevate positive mood states during the ascending limb of the BAC curve, but was associated with increased negative affect during the descending limb.

Acute alcohol intoxication, negative affect, and autonomic arousal in women and men

The present study tested the hypothesis that acute moderate alcohol intoxication is associated with reductions in experimentally-induced negative affect among 64 moderately drinking adult women and men. The effort incorporated a balanced placebo design, multiple measures of affective responses including cardiovascular and electrodermal activity, and control for phase of the sexual cycle among nonoral contraceptive women. Negative effect and psychophysiological responses to intoxication following stress manipulation were a complex function of beverage, expectancy, and gender. Expectation of a moderate alcohol dose among women at the premenstruum was associated with higher levels of self-reported anxiety, whereas alcohol consumption guised as tonic seemed to be related to tension reduction. Alcohol tended to increase autonomic arousal among men, but there were no significant changes in negative affect. Moderate intoxication was associated with increased heart rate regardless of gender, and alcohol expectancy increased levels of skin conductance for men and women.

In vivo regional levels of PGE and thromboxane in mouse brain: effect of decapitation, focused microwave fixation, and indomethacin.

A focused microwave fixation technique was tested for use in determining basal PGE and thromboxane B2 levels of mouse brain. Focused microwave irradiation (3.5 Kw/0.4 sec) to the head of C3H mice produced basal values of PGE and TXB2 which were five-fold less than those in animals killed by decapitation. Indomethacin (10 mg/kg) pretreatment blocked the decapitation rise in PGE and TXB2 levels and gave values similar to focused microwave irradiation. Indomethacin pretreatment combined with microwave fixation did not reduce PG levels more than microwave treatment alone. When microwave fixation was used, there was no difference in regional (cerebral cortex, whole cerebellum, midbrain, hypothalamus) levels of either PGE or TXB2. However, PGE levels were significantly higher than TXB2 in all regions. After decapitation there was a greater increase in TXB2 than PGE. The cerebellum produced less PGE and TXB2 after decapitation compared to the other regions. Our results confirm the usefulness of the focused microwave irradiation technique for examining in vivo basal prostaglandin levels in mouse brain.

Pharmacological Treatment of Alcohol Abuse/Dependence With Psychiatric Comorbidity

This article represents the proceedings of a symposium at the 2003 annual meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3) Pharmacological treatment of alcohol dependent patients with comorbid depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics: a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R. Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E. Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I. Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z. Litten. Alcohol-dependent individuals have exceptionally high rates of co-occurring psychiatric disorders. Although this population is more likely to seek alcoholism treatment than noncomorbid alcoholics, the prognosis for treatment is often poor, particularly among patients with more severe psychiatric illnesses. Development of effective interventions to treat this population is in the early stages of research. Although the interaction between the psychiatric condition and alcoholism is complex, progress has been made. The NIAAA has supported a number of state-of-the-art pharmacological and behavioral trials in a variety of comorbid psychiatric disorders. Some of these trials have been completed and are presented here. The symposium presented some new research findings from clinical studies with the aim of facilitating the development of treatments that improve alcohol and psychiatric outcomes among individuals with alcohol-use disorders and co-occurring psychiatric disorders. The panel focused on social anxiety disorder, depression, bipolar disorder, and schizophrenia.