A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances.

A cannabis withdrawal syndrome has been characterized, but its clinical significance remains uncertain. One method of assessing the significance of cannabis withdrawal is to compare it directly to an established withdrawal syndrome. The present study was a within-subject comparison of cannabis, tobacco, and combined cannabis and tobacco withdrawal among users of both substances. Participants (N=12) completed three 5-day periods of abstinence in a randomized order, separated by 9-day periods of usual substance use. Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted. These results are consistent with other evidence suggesting cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11. Additional research is needed to replicate these findings and to further investigate the effects of abstaining from multiple drugs simultaneously.

Complications following laryngeal sacculectomy in brachycephalic dogs.

OBJECTIVES: To evaluate the effect of sacculectomy on the immediate postoperative complication rate in dogs affected with brachycephalic obstructive airway syndrome. MATERIALS AND METHODS: Retrospective review of clinical records of brachycephalic dogs with everted saccules that underwent surgery for brachycephalic obstructive airway syndrome between 2009 and 2014. Dogs were grouped as those having nares resection and staphylectomy only and those having nares resection, staphylectomy and laryngeal sacculectomy. Complications were scored as mild, moderate or severe. RESULTS: In total, 37 dogs were included in the sacculectomy group and 44 in the comparator group. Dogs that had undergone sacculectomy were more likely to develop postoperative complications, with 18 of 37 developing complications, nine of which were moderate to severe. In the group without sacculectomy, nine of 44 dogs developed complications, of which one was severe. Different breed distribution between groups might also impact this outcome. CLINICAL SIGNIFICANCE: The results suggest that sacculectomy might increase morbidity following brachycephalic airway surgery, but repeat studies are required to confirm this result. Further information is also required to determine whether the short-term risks of sacculectomy are outweighed by superior long-term functional outcome.

Antidepressants for smoking cessation.

BACKGROUND: There are at least two theoretical reasons to believe antidepressants might help in smoking cessation. Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction, (e.g. blocking nicotine receptors) independent of their antidepressant effects. OBJECTIVES: The aim of this review is to assess the effect of antidepressant medications in aiding long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; sertraline, tryptophan and venlafaxine. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in September 2006. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow up. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the pharmacotherapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months follow up in patients smoking at baseline, expressed as an odds ratio (OR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: Seventeen new trials were identified since the last update in 2004 bringing the total number of included trials to 53. There were 40 trials of bupropion and eight trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (31 trials, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.72 to 2.19) and nortriptyline (four trials, OR 2.34, 95% CI 1.61 to 3.41) both doubled the odds of cessation. There is insufficient evidence that adding bupropion or nortriptyline to nicotine replacement therapy provides an additional long-term benefit. Three trials of extended therapy with bupropion to prevent relapse after initial cessation did not find evidence of a significant long-term benefit. From the available data bupropion and nortriptyline appear to be equally effective and of similar efficacy to nicotine replacement therapy. Pooling three trials comparing bupropion to varenicline showed a lower odds of quitting with bupropion (OR 0.60, 95% CI 0.46 to 0.78). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Concerns that bupropion may increase suicide risk are currently unproven. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation. There were six trials of selective serotonin reuptake inhibitors; four of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant long-term effects, and there was no evidence of a significant benefit when results were pooled. There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these detected a significant long-term benefit. AUTHORS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long-term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Adverse events with both medications are rarely serious or lead to stopping medication.

Signs and symptoms of tobacco withdrawal.

To test the validity, magnitude, and clinical significance of the signs and symptoms of tobacco withdrawal defined by DSM-III, both observed and reported signs and symptoms were measured in 50 smokers during two days of ad lib smoking and then during the first four days of abstinence. Observer and subject ratings of the DSM-III symptoms of craving for tobacco, irritability, anxiety, difficulty concentrating, and restlessness increased after cessation. In addition, bradycardia, impatience, somatic complaints, insomnia, increased hunger, and increased eating occurred after cessation. The frequency and intensity of these symptoms varied across subjects; however, the average distress from tobacco withdrawal was similar to that observed in psychiatric outpatients. Subjects who had more withdrawal discomfort were more tolerant to the cardiovascular effects of nicotine. Subjects who had more withdrawal discomfort did not have a lower rate of smoking cessation.

Marijuana abstinence effects in marijuana smokers maintained in their home environment.

BACKGROUND: Although withdrawal symptoms are commonly reported by persons seeking treatment for marijuana dependence, the validity and clinical significance of a marijuana withdrawal syndrome has not been established. This controlled outpatient study examined the reliability and specificity of the abstinence effects that occur when daily marijuana users abruptly stop smoking marijuana. METHODS: Twelve daily marijuana smokers were assessed on 16 consecutive days during which they smoked marijuana as usual (days 1-5), abstained from smoking marijuana (days 6-8), returned to smoking marijuana (days 9-13), and again abstained from smoking marijuana (days 14-16). RESULTS: An overall measure of withdrawal discomfort increased significantly during the abstinence phases and returned to baseline when marijuana smoking resumed. Craving for marijuana, decreased appetite, sleep difficulty, and weight loss reliably changed across the smoking and abstinence phases. Aggression, anger, irritability, restlessness, and strange dreams increased significantly during one abstinence phase, but not the other. Collateral observers confirmed participant reports of these symptoms. CONCLUSIONS: This study validated several specific effects of marijuana abstinence in heavy marijuana users, and showed they were reliable and clinically significant. These withdrawal effects appear similar in type and magnitude to those observed in studies of nicotine withdrawal.

Symptoms of tobacco withdrawal. A replication and extension.

Smokers (n = 315) who wished to quit were randomly assigned in a double-blind manner to groups using either nicotine or placebo gum. Self-reported and observed symptoms of tobacco withdrawal were collected before cessation and at follow-ups of 1 to 2 weeks, 1 month, and 6 months. Self-reported and/or observed anger, anxiety, craving, difficulty concentrating, hunger, impatience, and restlessness were the most prominent symptoms of tobacco withdrawal. These symptoms had returned to precessation levels by 1 month except increased weight, hunger, and craving continued for 6 months in many smokers. Nicotine gum decreased most symptoms, including craving and hunger but not weight. Abstinent smokers with more intense withdrawal were not more likely to relapse. Abstinent smokers who gained more weight were less likely to relapse.

Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers.

Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects.

A prospective study of off-label use of, abuse of, and dependence on nicotine inhaler.

OBJECTIVE: To determine the incidence of off-label use of, abuse of, and dependence on prescription nicotine inhaler. DESIGN: Prospective telephone and internet interviews for six months. PARTICIPANTS: 535 new inhaler users. MAIN OUTCOME: Structured interview about off-label use (that is, use of inhaler for non-cessation reasons or concurrent use of inhaler and cigarettes) and Diagnostic and statistical manual, fourth edition (DSM-IV) and International classification of diseases, 10th edition (ICD-10) criteria for abuse and dependence RESULTS: Although many used inhaler and cigarettes concurrently at some time (43-55%), few used inhaler for non-cessation reasons (4-9%) and few persisted in off label use (8-16%; 95% confidence interval (CI) 5% to 19%). No participant met ICD-10 criteria for harmful use/abuse (95% CI 0% to 3.3%). Eight subjects (1.4%) appeared to meet DSM-IV or ICD-10 criteria for dependence on inhaler, but none were found dependent in a clinical expert interview (95% CI 0% to 3.3%). CONCLUSIONS: Although transient concurrent use of inhaler and cigarettes often occurs, use for non-cessation reasons, abuse and dependence are rare.

Long-term use of nicotine vs placebo gum.

Medical patients (n = 315) who wished to quit smoking were randomly assigned in a double-blind manner to receive either nicotine or placebo gum. Subjects were advised to stop gum use by 4 months. Among abstinent smokers, 46% of those receiving nicotine gum and 17% of those receiving placebo gum used the gum beyond the recommended 4-month period. By 10 months after cessation 17% of quitters receiving nicotine gum and 6% receiving placebo gum were still using gum. Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain. We conclude that use of nicotine gum is due, in part, to the effects of nicotine; however, long-term use is uncommon.

Abuse liability of alprazolam relative to other commonly used benzodiazepines: a review.

Nonhuman and human studies comparing the abuse liability of alprazolam to other commonly used benzodiazepines are reviewed. These studies are reviewed to determine to what extent prospective, controlled, experimental studies support opinions that alprazolam's abuse liability is greater than that of other commonly used benzodiazepines. Studies comparing the self-administration of alprazolam, the discriminative stimulus effects of alprazolam, self-reported effects of alprazolam, physiological dependence on alprazolam, and adverse effects of alprazolam relative to other benzodiazepines are reviewed. Overall, the experimental literature does not support the widely held belief that alprazolam's abuse liability is greater than that of other benzodiazepines, but much more research is needed. Such research should focus explicitly on alprazolam's reinforcing effects, and the nature and severity of the discontinuation syndrome associated with its long-term use. Important issues such as selection of an appropriate comparison drug, selection of an appropriate population, dosing regimen and test doses need to be considered in future studies.

Evidence for psychopathology in patients with rhythmic midtemporal discharges.

In order to obtain further evidence of possible psychopathology, the Minnesota Multiphasic Personality Inventory (MMPI) was administered to 25 patients (pts) who had the controversial EEG pattern of rhythmic midtemporal discharges--(RMTD) psychomotor variant. The pts were divided into a retrospective and prospective group, the former consisting of only a minority (36%) of pts who had previously agreed to cooperate and the latter consisting of every pt (100%) showing the pattern in a 3-year period. The scores of all RMTD pts were abnormal (approximately 2 SD above the normal mean) for hypochondriasis, schizophrenia, depression, and hysteria and were classified as Abnormal on Rule 1 on the Goldberg sequential diagnostic system. Patients with intermediate or many bursts of this pattern were also classified as Abnormal, scored higher on every clinical scale, significantly so on five of the clinical scales and were significantly different with regard to the number of clinical scale scores at or over the T value of 70 as well as 80. The MMPI profile of RMTD pts is similar to those with definite temporal lobe epilepsy but different from pts with general medical disorders.

Psychiatric correlates of rhythmic midtemporal discharges and 6/sec spike and wave complexes.

In order to better characterize the psychopathology in patients with the two specific EEG patterns, rhythmic midtemporal discharges (RMTD) and 6/sec spike and wave complexes (S + W), the newly developed Diagnostic Interview Schedule (DIS) was administered to 40 patients in four groups. One group had RMTD, the other 6/sec S + W complexes; there were two control groups, both with normal electroencephalograms (EEGs), one group with, and the other without, a history of psychiatric illnesses. The RMTD group had significantly less symptomatology than the 6/sec S + W and the psychiatric control groups, but it had a significantly higher percentage of somatization symptoms; patients with 6/sec S + W showed a tendency toward anxiety-related disorders. The psychiatric control group had no specific trends, but demonstrated more overall psychopathology than the two groups with a specific EEG pattern.

Effects of caffeine on tobacco withdrawal.

Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal.

Prevalence of tobacco dependence and withdrawal.

In a sample of 1,006 middle-aged male smokers drawn from the general population, 90% (N = 905) fulfilled DSM-III criteria and 36% (N = 362) fulfilled Fagerstrom's criteria for tobacco dependence. Among the 875 who had stopped smoking in the past for at least 24 hours, 21% (N = 184) fulfilled DSM-III criteria and 46% (N = 403) fulfilled the authors' own criteria for tobacco withdrawal. Concordance of results among the criteria for diagnosing tobacco dependence and withdrawal was low. These results suggest that the DSM-III criteria for tobacco dependence are overinclusive and that there is little consensus among the definitions of tobacco dependence and withdrawal.

Prevalence of smoking among psychiatric outpatients.

The prevalence of smoking among psychiatric outpatients (N = 277) was significantly higher than among either local or national population-based samples (N = 1,440 and 17,000) (52% versus 30% and 33%). The higher prevalence was not associated with the age, sex, marital status, socioeconomic status, alcohol use, coffee use, or institutionalization of the psychiatric patients. Smoking was especially prevalent among patients with schizophrenia (88%) or mania (70%) and among the more severely ill patients. Hypotheses about why psychiatric patients are more likely to smoke and why they do not have a high rate of smoking-induced illnesses are presented.

Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?

OBJECTIVE: The authors reviewed basic science and clinical data on caffeine abuse, dependence, and withdrawal in order to make a conclusion about whether these disorders exist and should be included in DSM-IV and ICD-10. METHOD: Studies were located through computerized searches, reference sections of published articles, and written requests. RESULTS: The studies show that abstinence from caffeine induces a withdrawal syndrome of headache, fatigue, and drowsiness which begins within 12-24 hours and lasts about 1 week. The syndrome can be severe and appears to be one reason for continued use of coffee. The prevalence of this caffeine withdrawal syndrome is unknown. Use of caffeine may aggravate some common behavioral and medical disorders. In double-blind tests, a subset of coffee and soda drinkers reliably self-administered caffeinated beverages in preference to uncaffeinated beverages. Clinical indicators of dependence, such as difficulty stopping use of caffeine and use despite harm, have not been documented. CONCLUSIONS: Caffeine withdrawal but not caffeine abuse or dependence should be included as a diagnosis in DSM-IV and ICD-10. Future research should focus on whether some caffeine users exhibit clinical indicators of drug dependence.

Achieving cocaine abstinence with a behavioral approach.

OBJECTIVE: The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals. METHOD: The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens. RESULTS: Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group. CONCLUSIONS: This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence.

A behavioral approach to achieving initial cocaine abstinence.

OBJECTIVE: The aim of this study was to assess the efficacy of a behavioral treatment program for achieving initial cocaine abstinence in individuals enrolled in outpatient treatment for cocaine dependence. METHOD: Thirteen consecutively admitted outpatients were offered behavioral treatment consisting of contingency management procedures and the community reinforcement approach. Fifteen consecutively admitted outpatients were offered treatment with 12-step counseling. All 13 of the patients who were offered the behavioral treatment accepted it; 12 of the patients offered 12-step counseling accepted it. RESULTS: Eleven of the 13 patients in the behavioral treatment were retained for 12 weeks of treatment, compared with five of the 12 patients given 12-step counseling. Ten of the patients given behavioral therapy achieved 4 weeks of continuous cocaine abstinence, compared with only three of those given 12-step counseling. Six of the patients in the behavioral treatment group achieved 8 weeks, and three achieved 12 weeks; none of the patients in the 12-step counseling program achieved 8 weeks. CONCLUSIONS: The behavioral treatment described in this paper offers promise as an effective intervention for achieving initial cocaine abstinence. A randomized trial is underway to assess the generality of these findings.

Long-term clinical and EEG changes in patients with epilepsy.

I studied changes during a 15- to 40-year period in EEG paroxysms and clinical seizures on 1,645 EEG tracings. The most common paroxysm before other patterns was the frontal focus and after other patterns was the temporal focus. Most patterns changed in six to eight years and these EEG changes accurately predicted the type of later clinical attacks. The majority of our patients manifested a temporal spike. The incidence of bilateral foci, as opposed to unilateral temporal foci, increased with age at a rate of almost 1% per year; the clinical expression of developing bilateral temporal foci was seen in 34% of the patients. Right-sided foci usually required more than twice as much time to manifest bilaterality than did left-sided foci; all changes from temporal areas required shorter development times than those from parasagittal areas. The most common intrahemispheric change was lateral; anterior migration was not statistically more common than posterior migration.