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Topiramate Treatment of Alcohol Use Disorder in Clinical Practice

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Topiramate Treatment of Alcohol Use Disorder in Clinical Practice CE: M.S.; JAM-D-16-00003; Total nos of Pages: 5; JAM-D-16-00003 CLINICAL CASE CONFERENCE Topiramate Treatment of Alcohol Use Disorder in Clinical Practice Hussam Jefee-Bahloul, MD, Lantie Jorandby, MD, and Albert J. Arias, MD, MS 08/15/2018 on pR0X8mps8emMFe6SSjULcOvZdU7Lq92sVezWUqbDpikBtBa8dPs+x8jFMo+CspZ5E+TY5YMZQKrQAwY1b8dC/CITypGBtyI/TuXrHp5+MNSsd6YOAns1MMj9Atc5CqXrWirhh/uUTYs= by https://journals.lww.com/journaladdictionmedicine from Downloaded Downloaded from a 12-week trial of naltrexone (up to 100 mg daily dose) https://journals.lww.com/journaladdictionmedicine Topiramate is an anticonvulsant medication with increasingly strong without effect, though with poor adherence. He did not have evidence, supporting its use for treating alcohol use disorder (AUD) co-occurring psychiatric conditions. based on clinical trials. These clinical cases summarize the initiation He was started on a dose of 25 mg topiramate daily and titration of topiramate in AUD treatment. The core issues of which was titrated to twice daily after 1 week. He reported no patient selection, consideration of comorbid psychiatric and medical significant side effects after 2 weeks. He was titrated to 50 mg conditions, side-effect profile, safety and effectiveness are reviewed. bid after 4 weeks, and reported some mild cognitive side Addiction physicians should take a leading role in using topiramate effects. He reported that his alcohol intake was reduced to 6 to to treat AUDs, working with patients to balance the benefits of 8 beers daily. Urine ethyl glucuronide testing (EtG) weekly by pR0X8mps8emMFe6SSjULcOvZdU7Lq92sVezWUqbDpikBtBa8dPs+x8jFMo+CspZ5E+TY5YMZQKrQAwY1b8dC/CITypGBtyI/TuXrHp5+MNSsd6YOAns1MMj9Atc5CqXrWirhh/uUTYs= topiramate with the risk. suggested reduced drinking, though it remained indicative of continued alcohol use. Due to cognitive complaints, the dose Key Words: alcohol dependence, alcohol use disorder, alcoholism, was held at 50 mg twice daily. anticonvulsant, medication treatment, topiramate After 4 weeks, his cognitive complaints abated. He (J Addict Med 2018;xx: xxx–xxx) continued to drink >8 beers daily. His hepatitis C treatment was delayed due to continued alcohol use. His laboratory studies, including urine EtG and serum gamma glutamyl CASE DESCRIPTIONS transferase (GGT), demonstrated continued substantial alco- hol intake. At the 4-week mark, we increased the dose to Case 1 50 mg in the morning and 75 mg at bedtime for 2 weeks, then ur first case is a 56-year-old African American male increased again to 75 mg twice daily for 2 weeks. No further O with a 35-year history of alcohol use, hypertension, and side effects or complaints were reported. At week 8, he a recent diagnosis of hepatitis C. He started drinking alcohol reported a reduction of alcohol intake to 4 beers daily. He at age 21 while serving in the Army. He began with heavy had no further cognitive complaints or other side effects. drinking episodes on weekends, but his drinking escalated Urine EtGs and blood GGTs were trending down weekly. after discharge from the Army. In his mid to late 20s, he drank At 12 weeks, patient was tolerating 100 mg of top- up to 1 pint of vodka and 12 beers daily. He had lost many jobs iramate twice daily. He continued to report a lower level of due to excessive absence related to his alcohol use. As part of drinking and a reduced craving to drink. His side-effect profile the antiviral treatment evaluation for hepatitis C, the patient remained low, with little to no complaints of cognitive dulling. was referred for addiction treatment, and was required to Urine EtGs and blood GGT testing within the past 8 weeks complete 3 months of treatment before beginning antiviral demonstrated a reduced amount of alcohol intake. EtG level at therapy. week 12 was 980 ng/mL, which reduced from 1290 ng/mL at Initially, he reported alcohol intake of 12 to 16 beers week 8. Serum GGT was 50 IU/L at week 12 (within normal daily. He described themes of loss of control, cravings, limits for the assay at the laboratory), and reduced from disrupted relationships, and irritable mood related to his 195 IU/L at the date of topiramate initiation. alcohol use. He had tried disulfiram in the past, but reported nonadherence after 1 week. Additionally, he had gone through Case 2 A 52-year-old European American military veteran male, with a history of opioid use disorder (OUD), alcohol From the University of Massachusetts Medical School, Worcester, MA use disorder (AUD), and major depressive disorder, who was (HJ-B); Massachusetts General Hospital, Boston, MA (LJ); and Yale on in remission from both substance use disorders after 1.5 years 08/15/2018 University School of Medicine, New Haven, CT (HJ-B, AJA). Received for publication January 4, 2016; Revised September 8, 2016 of treatment with buprenorphine and an antidepressant. He accepted September 11, 2016. had been abstinent on acamprosate for almost a year, but had The authors disclose no conflicts of interest. discontinued it. There was a question of a slight relapse to Send correspondence to Albert J. Arias, MD, MS, 950 Campbell Rd #116A, alcohol after that, though the patient denied it, and increased West Haven, CT 06516. E-mail: [email protected]. frequency of monitoring with EtG rapidly returned the mea- Copyright ß 2018 American Society of Addiction Medicine ISSN: 1932-0620/16/0000-0001 surement to zero levels. After another 5 months of therapy DOI: 10.1097/ADM.0000000000000444 with no relapse to opioids or alcohol, he desired taper and J Addict Med Volume 00, Number 00, Month/Month 2018 1 Copyright © 2018 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited. CE: M.S.; JAM-D-16-00003; Total nos of Pages: 5; JAM-D-16-00003 Jefee-Bahloul et al. J Addict Med Volume 00, Number 00, Month/Month 2018 discontinuation from buprenorphine. He then started to drinking, the patient pre-emptively checked herself back experiencing alcohol craving while decreasing the dose of into residential substance use rehabilitation for a short stay (2 buprenorphine gradually. He was restarted on acamprosate weeks). She remained sober with confirmed biomarker testing 666 mg, 3 times daily, and the tapering dose of buprenorphine (EtG and GGT) another month later. After several months, the was held constant at 8 mg daily. However, the patient contin- naltrexone was discontinued and she remained sober at ued to have alcohol cravings 1 month after. 2 months after that while on just the topiramate, which is As the patient was still requesting a taper off of bupre- the last biomarker testing point. norphine, topiramate was added to the regimen for eventual cross-taper with acamprosate. Topiramate was titrated to DISCUSSION 200 mg daily over about 5 weeks, and the patient reported Topiramate is an anticonvulsant medication with strong no side effects. The patient noted elimination of alcohol evidence supporting its use for treating AUD based on clinical cravings with titration of the topiramate, had no relapse to trials. It is perhaps the most promising medication tested for alcohol, and was able to resume tapering of buprenorphine. that purpose to date. Topiramate is known to act via multiple EtGs were negative (at zero), and though there was an elevated pharmacologic mechanisms including GABA-A receptor GGT and slight elevation of both AST and ALT, this modulation and glutamate receptor blockade (Johnson and was attributed to his history of fatty liver and overweight, Ait-Daoud, 2010). Topiramate is hypothesized to reduce as the EtG and overall clinical picture were consistent drinking by attenuating positive reinforcement from alcohol with abstinence. (Johnson et al., 2007) and possibly also by reducing alcohol craving. In addition, a recent study suggests that the medica- Case 3 tion works by increasing a person’s self-efficacy for resisting A 55-year-old postmenopausal female, college-edu- heavy drinking (Kranzler et al., 2014) (see the accompanying cated, homemaker, mother of 2 sons (teenager and young review by Manhapra et al. in this issue for additional infor- adult), had a 20-year history of AUD, generalized anxiety mation on mechanism of action). disorder (GAD), and hypothyroidism. The patient had a In 1 randomized controlled trial, topiramate reduced history of good response to low-dose topiramate (<100 mg alcohol intake and cravings, and improved quality of life and daily), initially prescribed about 18 years ago during her first health (Johnson et al., 2003; Johnson, 2004). In a subsequent treatment attempts. It is reported by the patient that she then multisite trial, the topiramate group demonstrated reduced had a 5-year period of sobriety while on topiramate, combined obsessional thoughts and compulsions about alcohol, reduced with regular attendance of AA meetings. number of heavy drinking days, and reduced risk of relapse The patient has had numerous relapses over the years (Johnson et al., 2007; Johnson et al., 2008). Furthermore, in a and had been on topiramate several times. Notably, she reports recent meta-analysis (Blodgett et al., 2014), 7 randomized doing well on the medication, but would often stop taking it placebo controlled trials (RCTs) where evaluated, and top- and eventually relapse to alcohol. She described marital and iramate had a moderate effect size by increasing abstinence family stressors to almost always be the trigger for relapse. and reducing heavy drinking. Feinn et al. estimated the She had been to residential rehab facilities and detoxification number needed to treat (NNT) for topiramate based on out- several times. She had tried naltrexone once for a few weeks, comes from a recent trial as (overall NNT is 5.29, and but it made her feel sedated and ‘‘clumsy,’’ so she stopped it. adjusting with adverse events the NNT ranges between Possibly naltrexone was helpful in treating her alcohol use 6.12 and 7.52), which are more favorable than recent esti- though as she reports being sober during that time.
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