Top Research That May Change How You Treat Patients With Substance Use Disorders


The authors use a 3-step process to identify and evaluate published research with findings that are ready for-and that have a direct bearing on-clinical practice.

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We have identified and evaluated published research with findings that are ready for-and that have a direct bearing on-clinical practice. We used a 3-step process:

• Literature published July 2013 through June 2014 was searched for relevant study findings

• Psychiatric groups and colleagues were asked the following question: Of the research published July 1, 2013, through June 30, 2014, which had the most impact on the clinical practice of psychiatry?

• Post-publication reviews and commentaries in peer-reviewed journals helped us assess the final choices

Twenty papers were chosen on the basis of their clinical relevance, applicability, and quality.

Here we present, in the first of a series of brief articles, highlights from 4 studies and 1 review article.

Pharmacotherapy for alcohol use disorders

It is evident that alcohol use disorders (AUDs) are associated with considerable morbidity, mortality, and impaired quality of life. In a systematic review and meta-analysis to assess AUD treatments in an outpatient setting, the authors included 122 randomized controlled trials and 1 cohort study (N = 22,803).1 For all of the studies (reports published between 1970 and 2014), the duration of treatment was at least 12 weeks. Pooled analysis showed that oral acamprosate and naltrexone (50 mg/d) were the only FDA-approved treatments that were superior to placebo in preventing relapse.

The number needed to treat (NNT) to prevent return to any drinking was better for acamprosate than for naltrexone (12 vs 20, respectively); however, naltrexone was the superior treatment to prevent return to heavy drinking (NNT = 12). Both treatments also significantly decreased drinking days; naltrexone also reduced heavy drinking days and drinks per drinking day. Acamprosate and naltrexone did not differ on head-to-head comparison. Other effective treatments included naltrexone 100 mg/d for decreasing heavy drinking days; injectable naltrexone for reducing drinking days and heavy drinking days; nalmefene for reducing return to heavy drinking, heavy drinking days per month, and drinks per drinking day; valproic acid to prevent return to heavy drinking; and topiramate for decreasing drinking days, heavy drinking days, and drinks per drinking day. Acamprosate caused anxiety; naltrexone use led to dizziness and more GI adverse effects; topiramate was associated with neurological adverse effects; and there was a higher risk of withdrawal with naltrexone and nalmefene.

Given the mixed efficacy and underutilization of current FDA-approved treatments, development and examination of other drugs for AUDs is indicated. Gabapentin has lately been studied for AUDs. When used in association with alcohol consumption, gabapentin regulates neurotransmission, reduces cravings, and improves mood and sleep.

Mason and colleagues2 undertook a 12-week, double blinded, 3-arm, parallel-group, placebo-controlled outpatient study. Treatment-seeking alcohol-dependent adults (N = 150) were randomized to placebo, 900 mg of gabapentin, or 1800 mg of gabapentin. Study participants also received 20-minute weekly manual-guided counseling to improve treatment adherence.

Alcohol use was assessed by timeline followback interview, drinking diary, weekly breathalyzer, monthly γ-glutamyltransferase, and collateral information. This intent-to-treat analysis found that besides being well tolerated, gabapentin 1800 mg was the most effective treatment for abstinence (NNT = 8). It prevented heavy drinking (NNT = 5), and reduced heavy drinking days and drinks consumed per week. In addition, although the participants were minimally depressed at baseline, gabapentin 1800 mg showed statistically improved outcomes on mood, sleep, and craving measures.

Despite limitations such as higher heterogeneity, medium risk of bias among the studies in the meta-analysis1 along with attrition rate, and exclusion of comorbid substance use and psychiatric disorders in the gabapentin trial,2 these studies validated some already established treatments and provide insight into new ones.

Treatment for tobacco dependence

Study findings highlight the importance of identification and use of effective tobacco cessation treatments among persons with mental illness. Two studies examined the effects of motivationally targeted treatment or maintenance of pharmacological treatment on tobacco consumption outcomes.3,4

In the first study, 224 inpatients who were moderately nicotine-dependent smokers were randomized into either a smoking cessation intervention or usual care.3 Randomization was stratified by number of cigarettes smoked daily and state of change. The motivationally tailored intervention was initiated during inpatient stay and included an individually tailored computer-delivered program and tobacco cessation counseling as well as access to nicotine patches, support from an outpatient provider, and computer intervention post-hospitalization.

The study assessed biochemically verified 7-day point abstinence at follow-up and re-hospitalization rates during the 18-month period. Most study completers were in the contemplation stage of change and the retention rates were comparable in both groups. The abstinence rates were higher for the intervention group over 18 months (odds ratio [OR] = 3.15; 95% confidence interval [CI], 1.22 - 8.14). Psychiatric and substance use disorders did not predict abstinence at follow-up. More participants in usual care were hospitalized over the 18-month period (56% and 44%, respectively; OR = 1.92; 95% CI, 1.06 - 3.49). Abstinence status was not found to be associated with re-hospitalization, unlike other biopsychosocial variables.

Results from this study demonstrated that individually tailored, motivationally designed interventions along with nicotine replacement can lead to better rates of abstinence and fewer re-hospitalizations. This important finding may change practice, given that the abstinence rates have been found to decline considerably after discontinuation of pharmacological therapy.

In the double-blind, placebo-controlled second study, 87 patients who had achieved 2 weeks of continuous abstinence at week 12 on open treatment were randomized to cognitive-behavioral therapy (CBT) and varenicline (1 mg twice daily) or placebo.4 Patients continued treatment until week 52, after which treatment was discontinued; these patients were followed up to week 76. The outcome measures included 7-day continuous abstinence confirmed by exhaled carbon monoxide at week 52, biochemically confirmed continuous abstinence from weeks 12 through 64, and self-reported smoking behaviors until week 76. About 70% completed the relapse prevention phase (weeks 12 to 52).

The active-treatment group (varenicline and CBT) had tripling of 7-day continuous abstinence rates at week 52 (60% vs 19%; OR = 6.2; 95% CI, 2.2 - 19.2) and continuous abstinence from weeks 12 through 64 (45% vs 15%; OR = 4.6; 95% CI, 1.5 - 15.7). In addition, continuous abstinence as measured by patient self-report was higher in the active-treatment group (OR = 3.5; 95% CI, 1.02 - 13.6). Severity of psychiatric symptoms, overall health self-report, and nicotine withdrawal symptoms did not differ between groups. The active-treatment group had more headaches (P ≤ .05), less agitation or excitement (P ≤ .05), and fewer hospitalizations (risk ratio = 0.45; 95% CI, 0.04 - 2.9).

This study provides much-needed evidence for continuing maintenance combination treatment to achieve better tobacco cessation outcomes among psychiatric patients.

Marijuana use

To help educate patients and their families in face of the ever-increasing acceptability of cannabis, Volkow and colleagues5 from the National Institute on Drug Abuse (NIDA) summarized the effect of heavy or long-term marijuana use. Adolescent exposure to tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, alters the sensitivity of the brain’s reward regions to other substances. Moreover, brain circuitry is impaired; there is increased risk of mental illness as well as respiratory and cardiovascular problems; and academic performance and quality of life decline while higher school dropout and delinquent behavior rates increase.

The researchers also raised concerns about a possible correlation between increasing THC content and higher number of emergency department visits and motor vehicle accidents. Since adolescent marijuana use has been shown to be inversely related to the perceived risk of marijuana, Volkow and colleagues5 also speculated about the negative impact of new age permissiveness and the dynamic socio-politico-legal changes regarding marijuana on adolescent and adult health outcomes.


These studies emphasize established treatments and also provide information about new therapies that may improve outcomes. In our opinion, naltrexone and acamprosate should be the first-line treatments along with psychosocial interventions in isolated or comorbid AUD, and gabapentin may be used as a second-line treatment in a primary care population.

Pharmacological agents in combination with psychosocial support beyond the acute treatment phase of tobacco cessation are well tolerated and reduce recidivism.

Given pop culture and ever-changing legality, marijuana use continues to be a challenge. The review article by researchers at the NIDA is essential to our understanding the adverse effects of cannabis use not only by the pediatric population but by adults as well.


Dr Saeed is Professor and Chairman in the department of psychiatric medicine at the Brody School of Medicine at East Carolina University, Director of the ECU Center for Telepsychiatry and e-Behavioral Health as well as of the North Carolina Statewide Telepsychiatry Program (NC-STeP), and Chief of Psychiatry at the Vidant Medical Center in Greenville, NC. Dr Anand is an Assistant Professor and Dr Stanciu is a Second-Year Resident in the department of psychiatry and behavioral medicine at the Brody School of Medicine. The authors report no conflicts of interest concerning the subject matter of this article.


1. Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014;311:1889-1900.

2. Mason BJ, Quello S, Goodell V, et al. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174:70-77.

3. Prochaska JJ, Hall SE, Delucchi K, Hall SM. Efficacy of initiating tobacco dependence treatment in inpatient psychiatry: a randomized controlled trial. Am J Public Health. 2014;104:1557-1565.

4. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014; 311:145-154.

5. Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;370:2219-2227.

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