Browsing by Subject "Substance withdrawal syndrome"

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    Clinical interventions for adults with comorbid alcohol use and depressive disorders: A systematic review and network meta-analysis
    (Public Library of Science, 2021-10) Grant, Sean; Azhar, Gulrez; Han, Eugeniu; Booth, Marika; Motala, Aneesa; Larkin, Jody; Hempel, Susanne; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Uncertainty remains regarding the effectiveness of treatments for patients diagnosed with both an alcohol use disorder (AUD) and depressive disorder. This study aimed to compare the effectiveness of clinical interventions for improving symptoms of adults with co-occurring AUDs and depressive disorders. Methods and findings: We searched CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Excerpta Medica Database, International Clinical Trials Registry Platform (ICTRP), PubMed, PsycINFO, and Web of Science from inception to December 2020. We included randomized controlled trials (RCTs) evaluating clinical interventions for adults with co-occurring AUDs and depressive disorders. Two independent reviewers extracted study-level information and outcome data. We assessed risk of bias using the Cochrane Risk of Bias tool, used frequentist random effects models for network meta-analyses, and rated our confidence in effect estimates using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Primary outcomes were remission from depression and alcohol use. Secondary outcomes were depressive symptoms, alcohol use, heavy drinking, health-related quality of life, functional status, and adverse events. We used standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes to estimate intervention effects. Overall, 36 RCTs with 2,729 participants evaluated 14 pharmacological and 4 psychological interventions adjunctive to treatment as usual (TAU). Studies were published from 1971 to 2019, conducted in 13 countries, and had a median sample size of 50 participants (range: 14 to 350 participants). We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use). We have moderate confidence that cognitive behavioral therapies (CBTs) demonstrated greater benefit than no additional treatment (SMD = -0.84; 95% confidence interval [CI], -1.05 to -0.63; p < 0.001) for depressive symptoms and low confidence (SMD = -0.25; 95% CI, -0.47 to -0.04; p = 0.021) for alcohol use. We have low confidence that tricyclic antidepressants (TCAs) demonstrated greater benefit than placebo (SMD = -0.37; 95% CI, -0.72 to -0.02, p = 0.038) for depressive symptoms. Compared with placebo, we have moderate confidence that selective serotonin reuptake inhibitors (SSRIs) demonstrated greater benefit for functional status (SMD = -0.92; 95% CI, -1.36 to -0.47, p < 0.001) and low confidence for alcohol use (SMD = -0.30; 95% CI, -0.59 to -0.02, p = 0.039). However, we have moderate confidence that patients receiving SSRIs also were more likely to experience an adverse event (OR = 2.20; 95% CI, 0.94 to 5.16, p = 0.07). We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates. Limitations include the sparsity of evidence on intervention effects over the long term, risks of attrition bias, and heterogeneous definitions of adverse events in the evidence base. Conclusions: We are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest that CBTs likely reduced, and TCAs may have resulted in a slight reduction of depressive symptoms. SSRIs likely increased functional status, and SSRIs and CBTs may have resulted in a slight reduction of alcohol use. However, patients receiving SSRIs also likely had an increased risk of experiencing an adverse event. In addition, these conclusions only apply to postintervention and are not against active comparators, limiting the understanding of the efficacy of interventions in the long term as well as the comparative effectiveness of active treatments. As we did not have high confidence in any outcomes, additional studies are warranted to provide more conclusive evidence.
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    Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations
    (Oxford Academic, 2017-01) Rasmussen, Dennis D.; Kincaid, Carrie L.; Froehlich, Janice C.; Medicine, School of Medicine
    AIMS: Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α1-adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. METHODS: Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. RESULTS: Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. CONCLUSION: Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. SHORT SUMMARY: Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated alcohol deprivations may prevent the increased anxiety that is a risk factor for relapse to alcohol drinking
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    Spontaneous Early Withdrawal Behaviors after Chronic 24-hour Free-Choice Access to Ethanol
    (Oxford University Press, 2020-08-14) Hauser, Sheketha R.; Smith, Rebecca J.; Toalston, Jamie E.; Rodd, Zachary A.; McBride, William J.; Bell, Richard L.; Psychiatry, School of Medicine
    Aims: Abstinence after chronic alcohol consumption leads to withdrawal symptoms, which are exacerbated after repeated cycles of relapse. This study examined withdrawal-like behaviors after chronic ethanol drinking, with or without repeated cycles of deprivation. Methods: Male alcohol-preferring (P) rats had access to continuous ethanol (CE), chronic ethanol with repeated deprivation (RD), or remained ethanol naïve (EN). The RD group experienced seven cycles of 2 weeks of deprivation and 2 weeks of re-exposure to ethanol after an initial 6 weeks of ethanol access. Withdrawal was measured after an initial 24 h of ethanol re-exposure in the RD group, which coincided with the same day of ethanol access in the CE group. Withdrawal-like behavior was measured by (a) ethanol intake during the initial 24 h of re-exposure, (b) locomotor activity (LMA) in a novel field 9-13 h after removal of ethanol at the beginning of the fifth re-exposure cycle and (c) acoustic startle responding (ASR) 8-15 h after removal of ethanol at the beginning of the sixth re-exposure cycle. Results: The RD rats displayed a 1-h alcohol deprivation effect (ADE) (temporary ethanol increase), relative to CE rats, during the first to fourth and seventh re-exposure cycles. RD and CE rats displayed significant increases in LMA than EN rats. Regarding ASR, RD rats displayed significantly greater ASR relative to EN rats. Conclusion: This study confirms that P rats meet the animal model criterion for ethanol-associated dependence, without a reliance on either behavioral (limited fluid access) or pharmacological (seizure threshold manipulation) challenges.