1. Home
  2. substance withdrawal syndrome

substance withdrawal syndrome

Maintenance or Discontinuation of Antidepressants in Primary Care

Author/s: 
Lewis, G., Marston, L., Duffy, L., Freemantle, N., Gilbody, S., Hunter, R., Kendrick, T., Kessler, D., Mangin, D., King, M., Lanham, P., Moore, M.

BACKGROUND
Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.

METHODS
We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.

RESULTS
A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.

CONCLUSIONS
Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

Unhealthy alcohol use in a 65-year-old man awaiting surgery

Author/s: 
Brothers, T. D., Kaulbach, J., Tran, A.

Three months before elective hip arthroplasty, a 65-yearold man with osteoarthritis presents to his family physician to discuss his alcohol consumption. His surgeon had expressed concern and advised him to speak to his family physician about decreasing his drinking before surgery. He reports drinking around 6 to 10 ounces of whiskey daily for the past 5 years. His alcohol intake increased gradually after retirement, and he now has cravings daily. He recently abstained from alcohol for 4 days while visiting family and developed irritability, tremor, nausea and headache. He has never had withdrawal seizures or delirium tremens, and he does not use any other substances. He is otherwise healthy, apart from hypertension that is controlled with perindopril. He is alarmed by his cravings, withdrawal symptoms and surgeon’s concerns, and is considering decreasing his alcohol use.

Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids: A Systematic Review and Meta-analysis

Author/s: 
Bahji, A., Stephenson, C., Tyo, R., Hawken, E.R., Seitz, D.P.

IMPORTANCE: 

Cannabis withdrawal syndrome (CWS)-a diagnostic indicator of cannabis use disorder-commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS.

OBJECTIVES: 

To estimate the prevalence of CWS among individuals with regular or dependent use of cannabinoids and identify factors associated with CWS.

DATA SOURCES: 

A search of literature from database inception to June 19, 2019, was performed using MEDLINE, Embase, PsycINFO, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, ProQuest, Allied and Complementary Medicine, and Psychiatry online, supplemented by manual searches of reference lists of included articles.

STUDY SELECTION: 

Articles were included if they (1) were published in English, (2) reported on individuals with regular use of cannabinoids or cannabis use disorder as a primary study group, (3) reported on the prevalence of CWS or CWS symptoms using a validated instrument, (4) reported the prevalence of CWS, and (5) used an observational study design (eg, cohort or cross-sectional).

DATA EXTRACTION AND SYNTHESIS: 

All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. Cannabis withdrawal syndrome prevalence was estimated using a random-effects meta-analysis model, alongside stratification and meta-regression to characterize heterogeneity.

MAIN OUTCOMES AND MEASURES: 

Cannabis withdrawal syndrome prevalence was reported as a percentage with 95% CIs.

RESULTS: 

Of 3848 unique abstracts, 86 were selected for full-text review, and 47 studies, representing 23 518 participants, met all inclusion criteria. Of 23 518 participants included in the analysis, 16 839 were white (72%) and 14 387 were men (69%); median (SD) age was 29.9 (9.0) years. The overall pooled prevalence of CWS was 47% (6469 of 23 518) (95% CI, 41%-52%), with significant heterogeneity between estimates (I2 = 99.2%). When stratified by source, the prevalence of CWS was 17% (95% CI, 13%-21%) in population-based samples, 54% in outpatient samples (95% CI, 48%-59%), and 87% in inpatient samples (95% CI, 79%-94%), which were significantly different (P < .001). Concurrent cannabis (β = 0.005, P < .001), tobacco (β = 0.002, P = .02), and other substance use disorders (β = 0.003, P = .05) were associated with a higher CWS prevalence, as was daily cannabis use (β = 0.004, P < .001).

CONCLUSIONS AND RELEVANCE: 

These findings suggest that cannabis withdrawal syndrome appears to be prevalent among regularusers of cannabis. Clinicians should be aware of the prevalence of CWS in order to counsel patients and support individuals who are reducing their use of cannabis.

Keywords 
cannabis cannabis use withdrawl predictors

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial

Author/s: 
Anton, R.F., Latham, P., Voronin, K., Book, S., Hoffman, M., Bristol, E., Prisciandaro, J.

OBJECTIVE: 

To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcoholwithdrawal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: 

This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawalcriteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.

INTERVENTIONS: 

Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each).

MAIN OUTCOMES AND MEASURES: 

The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms.

RESULTS: 

Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.

CONCLUSIONS AND RELEVANCE: 

These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.

TRIAL REGISTRATION: 

ClinicalTrials.gov Identifier: NCT02349477.

Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation

Author/s: 
Lindson, Nicola, Chepkin, Samantha C., Ye, Weiyu, Fanshawe, Thomas R., Bullen, Chris, Hartmann-Boyce, Jamie

BACKGROUND:

Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes to ease the transition from cigarette smoking to abstinence. It works by reducing the intensity of craving and withdrawal symptoms. Although there is clear evidence that NRT used after smoking cessation is effective, it is unclear whether higher doses, longer durations of treatment, or using NRT before cessation add to its effectiveness.

OBJECTIVES:

To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long-term smoking cessation, compared to one another.

SEARCH METHODS:

We searched the Cochrane Tobacco Addiction Group trials register, and trial registries for papers mentioning NRT in the title, abstract or keywords. Date of most recent search: April 2018.

SELECTION CRITERIA:

Randomized trials in people motivated to quit, comparing one type of NRT use with another. We excluded trials that did not assess cessation as an outcome, with follow-up less than six months, and with additional intervention components not matched between arms. Trials comparing NRT to control, and trials comparing NRT to other pharmacotherapies, are covered elsewhere.

DATA COLLECTION AND ANALYSIS:

We followed standard Cochrane methods. Smokingabstinence was measured after at least six months, using the most rigorous definition available. We extracted data on cardiac adverse events (AEs), serious adverse events (SAEs), and study withdrawals due to treatment. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate, using a Mantel-Haenszel fixed-effect model.

MAIN RESULTS:

We identified 63 trials with 41,509 participants. Most recruited adults either from the community or from healthcare clinics. People enrolled in the studies typically smoked at least 15 cigarettes a day. We judged 24 of the 63 studies to be at high risk of bias, but restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results, apart from in the case of the preloading comparison. There is high-certainty evidence that combination NRT (fast-acting form + patch) results in higher long-term quit rates than single form (RR 1.25, 95% CI 1.15 to 1.36, 14 studies, 11,356 participants; I2 = 4%). Moderate-certainty evidence, limited by imprecision, indicates that 42/44 mg are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93 to 1.29, 5 studies, 1655 participants; I2 = 38%), and that 21 mg are more effective than 14 mg (24-hour) patches (RR 1.48, 95% CI 1.06 to 2.08, 1 study, 537 participants). Moderate-certainty evidence (again limited by imprecision) also suggests a benefit of 25 mg over 15 mg (16-hour) patches, but the lower limit of the CI encompassed no difference (RR 1.19, 95% CI 1.00 to 1.41, 3 studies, 3446 participants; I2 = 0%). Five studies comparing 4 mg gum to 2 mg gum found a benefit of the higher dose (RR 1.43, 95% CI 1.12 to 1.83, 5 studies, 856 participants; I2 = 63%); however, results of a subgroup analysis suggest that only smokers who are highly dependent may benefit. Nine studies tested the effect of using NRT prior to quit day (preloading) in comparison to using it from quit day onward; there was moderate-certainty evidence, limited by risk of bias, of a favourable effect of preloading on abstinence (RR 1.25, 95% CI 1.08 to 1.44, 9 studies, 4395 participants; I2 = 0%). High-certainty evidence from eight studies suggests that using either a form of fast-acting NRT or a nicotine patch results in similar long-term quit rates (RR 0.90, 95% CI 0.77 to 1.05, 8 studies, 3319 participants; I2 = 0%). We found no evidence of an effect of duration of nicotine patch use (low-certainty evidence); 16-hour versus 24-hour daily patch use; duration of combination NRT use (low- and very low-certainty evidence); tapering of patch dose versus abrupt patch cessation; fast-acting NRT type (very low-certainty evidence); duration of nicotine gum use; ad lib versus fixed dosing of fast-acting NRT; free versus purchased NRT; length of provision of free NRT; ceasing versus continuing patch use on lapse; and participant- versus clinician-selected NRT. However, in most cases these findings are based on very low- or low-certainty evidence, and are the findings from single studies.AEs, SAEs and withdrawals due to treatment were all measured variably and infrequently across studies, resulting in low- or very low-certainty evidence for all comparisons. Most comparisons found no evidence of an effect on cardiac AEs, SAEs or withdrawals. Rates of these were low overall. Significantly more withdrawals due to treatment were reported in participants using nasal spray in comparison to patch in one trial (RR 3.47, 95% CI 1.15 to 10.46, 922 participants; very low certainty) and in participants using 42/44 mg patches in comparison to 21/22 mg patches across two trials (RR 4.99, 95% CI 1.60 to 15.50, 2 studies, 544 participants; I2 = 0%; low certainty).

AUTHORS' CONCLUSIONS:

There is high-certainty evidence that using combination NRT versus single-form NRT, and 4 mg versus 2 mg nicotine gum, can increase the chances of successfully stopping smoking. For patch dose comparisons, evidence was of moderate certainty, due to imprecision. Twenty-one mg patches resulted in higher quit rates than 14 mg (24-hour) patches, and using 25 mg patches resulted in higher quit rates than using 15 mg (16-hour) patches, although in the latter case the CI included one. There was no clear evidence of superiority for 42/44 mg over 21/22 mg (24-hour) patches. Using a fast-acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate-certainty evidence that using NRT prior to quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is of low and very low certainty. New studies should ensure that AEs, SAEs and withdrawals due to treatment are both measured and reported.

Keywords 
smoking nicotine tobacco use risk

Tapering Long-term Opioid Therapy in Chronic Noncancer Pain: Evidence and Recommendations for Everyday Practice

Author/s: 
Berna, Chantal, Kulich, Ronald J., Rathmell, James P.

Increasing concern about the risks and limited evidence supporting the therapeutic benefit of long-term opioid therapy for chronic noncancer pain are leading prescribers to consider discontinuing the use of opioids. In addition to overt addiction or diversion, the presence of adverse effects, diminishing analgesia, reduced function and quality of life, or the absence of progress toward functional goals can justify an attempt at weaning patients from long-termopioid therapy. However, discontinuing opioid therapy is often hindered by patients' psychiatric comorbidities and poor coping skills, as well as the lack of formal guidelines for the prescribers. The aim of this article is to review the existing literature and formulate recommendations for practitioners aiming to discontinue long-term opioid therapy. Specifically, this review aims to answer the following questions: What is an optimal opioid tapering regimen? How can the risks involved in a taper be managed? What are the alternatives to an opioid taper? A PubMed literature search was conducted using the keywords chronic pain combined with opioidwithdrawal, taper, wean and detoxification. Six hundred ninety-five documents were identified and screened; 117 were deemed directly relevant and are included. On the base of this literature review, this article proposes evidence-based recommendations and expert-based suggestions for clinical practice. Furthermore, areas of lack of evidence are identified, providing opportunities for further research.

Keywords 
opiods taper pain management
Subscribe to substance withdrawal syndrome