Needs Assessment: Many clinicians have little information about the newer medications used to treat addiction, and often hold biases against using medications in the treatment of addiction. This paper places medications within the full context of addiction treatment and provides guidance on how to select and use the anti-addiction medications.
• Place medications within the context of full treatment for addiction
• List the Food and Drug Administration-approved medications for alcohol dependence
• Give an example of common side effects for varenicline
• Know the usual effective dose for buprenorphine
Target Audience: Primary care physicians and psychiatrists.
CME Accreditation Statement: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.
Credit Designation: The Mount Sinai School of Medicine designates this educational activity for a maximum of 3 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Faculty Disclosure Policy Statement: It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the course material.
This activity has been peer-reviewed and approved by James C.-Y. Chou, MD, associate professor of psychiatry at the Mount Sinai School of Medicine, and Norman Sussman, MD, editor of Primary Psychiatry and professor of psychiatry at New York University School of Medicine. Review Date: November 20, 2008.
Dr. Sussman reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Chou receives honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, and Pfizer.
To receive credit for this activity: Read this article and the two CME-designated accompanying articles, reflect on the information presented, and then complete the CME posttest and evaluation. To obtain credits, you should score 70% or better. Early submission of this posttest is encouraged: please submit this posttest by December 1, 2010 to be eligible for credit. Release date: December 1, 2008. Termination date: December 31, 2010. The estimated time to complete all three articles and the posttest is 3 hours.
Primary Psychiatry. 2008;15(12):73-80
Dr. Westreich is an associate professor of clinical psychiatry and Dr. Finklestein is an instructor in clinical psychiatry in the Department of Psychiatry’s Division on Alcoholism and Drug Abuse at New York University School of Medicine in New York City.
Disclosures: The authors report no affiliation with or financial interest in any organization that may pose a conflict of interest.
Off-label disclosure: This article contains discussion of the following unapproved medications for the treatment of addiction: baclofen, citalopram, flumazanil, fluoxetine, gabapentin, gamma-vinyl GABA, hydralazine, modafinil, propranolol, tiagabine, and topiramate.
Please direct all correspondence to: Deborah Finklestein, MD, Instructor in Clinical Psychiatry, Division on Alcoholism and Substance Abuse, Department of Psychiatry, New York University School of Medicine, 550 First Ave, New York, NY 10016; Tel: 212-579-4142; Fax: 212-579-7849; E-mail: email@example.com.
Can new medications help in the treatment of substance use disorders? The short answer to that question is yes. Despite the historical resistance of addiction treaters to using medications in their treatment of addicted people, recent advances and more sophisticated methods for integrating medications into standard addiction treatment have led to a surge in new anti-addiction medications available to the addicted person. Medications like depot naltrexone and acamprosate have shown substantial effects in decreasing alcohol craving, while suboxone has provided relief to opiate addicts who simply would not have come to treatment in the past. Despite the apparent post-marketing emergence of side effects like agitation and nightmares, varenicline is a step in the right direction for those looking for help with their nicotine addiction. Although not yet available to the public, the pipeline of investigational medications includes several cocaine vaccines. In addition to these vaccines and the Food and Drug Administration-approved medications, other addiction remedies have been touted in the press and should be understood by the general physician; in this widely publicized but unproven category is the proprietary medication “cocktail” offered by Prometa. Clinicians can provide substantial benefit to their addicted patients by making newly developed medications part of the treatment package. This article reviews the clinical use of these new medications.
The Epidemiologic Catchment Area study1 noted that 7.9% of the general population suffered from alcohol dependence over their lifetime, while 4.4% suffered from drug dependence. Despite some leveling off of teenager’s use of addictive substances over the past decade, 9.2% of all high school seniors acknowledged illicit use of non-heroin narcotics such as acetaminophen plus hydrocodone.2 However, these numbers do not reflect the desperation that addicted people, their loved ones, and their clinicians feel when confronted with a life-threatening addiction. Their anguish often engenders hope for a “magic pill” which will cure the addiction and return the sufferer to his or her previous state of health.
Despite the promise of some older medications as well as the medications reviewed below, no such panacea exists. The absence of such a curative biologic remedy arises in part from the remedial nature of understanding of addiction’s biology, and in part from the inherent impossibility of the task. No biologic substance will cure addiction since addiction is not (purely) a biologic condition. The successes of relapse prevention psychotherapy,3 network therapy,4 and other biopsychosocial treatments as well as peer-led support groups like Alcoholics Anonymous5 attest to the potential for effective non-biologic treatment of addiction.
However, biologic treatments like the medications in this article can substantially benefit the addicted person. Despite some resistance in the field of addiction psychiatry, most clinicians now see medications as a useful adjunct, if not the mainstay of treatment. Considerable controversy remains about the use of maintenance prescription of opiates, as with buprenorphine. But there is little disagreement about the need for more and better biologic approaches to the treatment of addiction. The medications below represent the newest and best of those approaches.
Since the 1970s, behavioral treatments6-8 have proven the most prevalent form of treatment in the United States. However, in the last several years, pharmacologic research has introduced some new medications as another means to enhance abstinence and prevent relapse.
The US Food and Drug Administration has approved disulfiram, acamprosate, and naltrexone (the latter in both daily oral and monthly injectable formulations) for the treatment of alcohol dependence. Previous articles1,2 have outlined the clinical uses of disulfiram and oral naltrexone. This article provides an update on the above medications as well as describes the applications of depot naltrexone and acamprosate, medications that are currently being used in the treatment of alcohol dependence.
Since the 1970s, disulfiram has been widely used as a deterrent to alcohol use secondary to its unpleasant side effects when alcohol is consumed. As a result, disulfiram primarily benefits patients who are adherent or receive medication under supervision. Controlled studies9-11 of disulfiram have revealed mixed results. Some provide evidence that drinking frequency is reduced, but the data show no convincing and sustained improvement in continuous abstinence rates. However, it still appears to be one of the most used pharmacotherapies available in the market and is dosed daily at 500 mg/day.
Naltrexone Oral Formulation
In 1994, naltrexone was approved by the FDA to treat alcohol dependence. An opioid antagonist, naltrexone is thought to dampen the pleasurable effects of alcohol-induced endogenous upload activity in the brain, thus reducing drinking frequency and the likelihood of relapse to heavy drinking.12,13 The standard regimen is one 50-mg tablet per day; duration of treatment can vary depending on the patient’s needs, but usually does not exceed 12 months. Initial nausea usually subsides after a few days, and other side effects (eg, heightened liver enzymes) are rare but necessitate monitoring of liver function tests.
Multiple controlled studies12,14-16 have shown naltrexone’s superiority over placebo, as patients receiving naltrexone were shown to be less likely to relapse to heavy drinking and more likely to drink on fewer days. Additionally, several meta-analyses17,18 have added support for the efficacy of naltrexone for improved abstinence. Other studies, however, have reported no or minimal effectiveness, attributing the outcome to poor medication adherence and adverse effects, especially nausea.19,20
Despite these findings, some patients find naltrexone helpful in itself or as an adjunct to other psychopharmacologic or psychosocial treatments. Clinicians should consider it as possiblity in treating their alcohol-dependent patients.
Naltrexone Depot Formulation
In an attempt to improve patient adherence and avoid some of the adverse effects associated with oral naltrexone, a monthly injectable formulation was approved by the FDA in April 2006. This formulation is administered by intramuscular (IM) injection of 380 mg and lasts for up to 30 days. Patients are advised to abstain from alcohol 3–7 days prior to first dose, but one study18 reported positive results in actively drinking patients with little to no abstinence period. Although FDA guidelines indicate that naltrexone should be used for up to 3 months to treat alcoholism, the Substance Abuse and Mental Health Administration (SAMHSA) recommends that treatment providers individualize the length of naltrexone treatment according to each patient’s needs. Certain patients may be appropriate candidates for long-term (eg, up to 1 year) naltrexone treatment if they demonstrate evidence of compliance with medication and psychosocial treatment regimens.
To date, the most reported adverse event has been injection site reactions. The FDA has received 196 reports of injection site reactions including cellulitis, induration, hematoma, abscess, sterile abscess, and necrosis, 16 of which required surgical intervention. In response to this, the FDA has recently issued an alert to healthcare professionals who are administering naltrexone to their patients. The recommendations are as follows:
Physicians who administer naltrexone should refer a patient who develops pain, swelling, bruising, pruritus, and redness at the injection site that does not improve within 2 weeks of naltrexone administration to a surgeon. Naltrexone should be administered as directed as an intramuscular (IM) gluteal injection. Naltrexone should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Healthcare providers should ensure that the naltrexone injection is given correctly with the pre-packaged 1.5-inch needle that is specifically designed for this drug. In addition, the FDA reports data that shows women may be physiologically at higher risk for injection site reactions due to typically higher gluteal fat thickness.3
Several studies4,5 demonstrate that long-acting naltrexone is well tolerated and associated with a significant reduction in heavy drinking in a population of actively drinking patients. In one recent study,21 the abstinence rate was significantly higher for IM naltrexone compared with placebo: median time to first drink was 41 days versus 12 days, respectively, and rate of continuous abstinence at end of the study was 32% versus 11% (P=.02). In addition, the patients who received naltrexone extended release (ER) showed substantially increased time to first heavy drinking event (>180 days vs. 20 days; P=.04) and decreased the median number of any drinking days per month by 90% (0.7 days vs. 7.2 days; P=.005) and heavy drinking days per month by 93% (0.2 days vs. 2.9 days; P=.007).
However, more data are needed to determine whether this treatment would similarly benefit alcohol-dependent women. Adverse events associated with the depot formulation appear to be milder than those associated with the use of oral naltrexone, but a direct comparison between the oral and depot formulations within the same clinical trial has yet to be studied.
In 2004, following use of acamprosate in Europe for more than a decade, the FDA approved this drug for treatment of alcohol dependence. Acamprosate targets the brain’s glutamate system and has been shown in European metanalyses to reduce the motivation to drink.22 However, several US studies23,24 have found it to have little efficacy, especially in non-motivated and non-abstinent populations. The reason for these contradictory results is unclear, but researchers speculate that they may reflect differences in patient characteristics included in the European and US studies as well as study designs. One early observational study25 suggested that acamprosate is useful in heavy drinking populations and is safe for use even early in the alcohol detoxification process. Trials continue and many researchers in the US and abroad continue to support the efficacy of acamprosate in maintaining abstinence and reducing alcohol consumption.26,27
Acamprosate is dosed as a 333-mg tablet TID and treatment duration can vary from 3–12 months. It is generally well tolerated and adverse events tend to be mild and transient, primarily involving the gastrointestinal tract with diarrhea and abdominal discomfort in approximately 10% of patients. Acamprosate should not be taken by those with kidney problems or allergies to the drug.28
Despite the overall plateau in illicit drug use in the US, opioid dependence remains a growing and deadly affliction. The number of current US heroin users rose from 136,000 in 2005 to 338,000 in 2006,29 while admissions for heroin dependence treatment actually decreased over the same 2 years.30 One out of every 20 high school seniors reported having tried oxycodone over the previous year31 and many, if not most, opioid-related deaths were due to misuse and abuse of prescription opioids.32
In the 50 years since the introduction of methadone, clinicians have had few other effective medications for opioid addiction until the FDA’s approval of suboxone in October 2002. Previous articles have outlined the clinical applications of methadone for detoxification and opioid maintenance,33 naltrexone for opioid blockade,34 and clonidine for opioid detoxification.35 Levo-a-acetyl-methadol, a previously available opioid agonist, was taken off the market in early 2004 because of cardiac side effects.36 This article reviews the clinical usage of the newer medications buprenorphine and injectable depot naltrexone and outlines the case against Prometa in the treatment of opioid addiction.
Buprenorphine, a partial opioid agonist, was approved by the FDA and became commercially available in January 2003 with a sublingual tablet as a sole agent as well as in a preparation mixed with naloxone, designed to prevent illicit intravenous use.
Under the auspices of the Drug Addiction Treatment Act of 2000,37 office-based physicians with special licenses were permitted to prescribe buprenorphine and other opioid medications for the treatment of addiction for the first time. The required training for these special licenses, in the form of an 8-hour course, is available from professional organizations like the American Academy of Addiction Psychiatry.38
Like methadone, buprenorphine can be used in a tapering protocol for detoxification or at stable dose for opioid maintenance. The differences between buprenorphine and methadone are substantial; buprenorphine can be prescribed in a private physician’s office, it has a “ceiling effect” which makes overdose unlikely, and its partial opioid agonism makes addictive use less likely, though far from impossible. Buprenorphine does not, as yet, engender the same sort of societal stigma as methadone, so the medication is acceptable to a cohort of opioid-dependent individuals who would avoid methadone clinics.
After determining that the patient is appropriate for either buprenorphine detoxification or maintenance, the treating clinician arranges a medication induction. One good source for treatment planning, SAMHSA’s Clinical Guide for the Use of Buprenorphine in the Treatment of Opioid Addiction,39 recommends (amongst other things) that the prospective patient choose buprenorphine after reviewing all the treatment options, be reasonably complaint, understand the risk and benefits of treatment, and not be dependent on other central nervous system (CNS) depressants like benzodiazepines and alcohol.
Induction onto buprenorphine can be complicated, especially with a patient who is less than fully compliant. Standard recommendations for induction40 suggest that the patient show actual withdrawal symptoms before a test dosage of buprenorphine 2–4 mg is administered, followed by close observation of withdrawal symptoms, with a first-day total maximum dosage of 8 mg and a second-day maximum dosage of 16 mg.
Once stabilized on buprenorphine, patients clearly benefit in terms of opioid avoidance. One outpatient study41 compared buprenorphine, buprenorphine/naloxone, and placebo in the treatment of 326 opiate-addicted people. The high efficacy of both buprenorphine preparations necessitated in preventing illicit opioid use necessitated an early end to the study; the subjects’ urine toxicologies at 4 weeks and self-reported opioid craving were both so low that the study was stopped and the placebo group was offered active medication.
In comparison to methadone, buprenorphine is similarly effective at the higher dosage range. One study42 of 116 opioid-dependent subjects compared high and low doses of both buprenorphine and methadone and found (predictably) that at 24 weeks, opioid positive urine toxicologies were highest (77% and 72%) in those randomly assigned to take the low doses of methadone 20 mg/day and buprenorphine 4 mg/day. Conversely, opioid-positive urine toxicology rates were lowest for those assigned to high doses of methadone 65 mg/day and buprenorphine 12 mg/day, at 45% and 58%, respectively.
One exciting possibility for buprenorphine is a depot preparation which can last 6 months. In Phase III FDA clinical trials,43 the 6-month depot form of buprenorphine was found to be better than placebo in preventing opioid use and very unlikely to be used illicitly, both to a very high degree of statistical significance (P=.0117 and P=.0004, respectively).
Naltrexone, a highly effective and long-lasting opioid receptor antagonist, is approved by the FDA, as noted above, as an anti-craving agent for alcohol. The 2008 Physician’s Desk Reference notes that naltrexone “…is not indicated for the purpose of opioid blockade or the treatment of opiate dependence…”44 because of the possibility that patients will attempt to overwhelm the opiate blockade and suffer respiratory collapse. Despite this rather overstated warning, (those taking oral naltrexone could try to overwhelm the blockade also,) clinicians have made the obvious maneuver of using naltrexone in their opioid-addicted patients. One preliminary study45 of IM naltrexone ER in 27 opioid-using adults found that blockade of hydromorphone as measured by pupil size and a visual analog scale of reported drug effect was complete for 28 days, based on dosages of IM naltrexone ER 150 mg and 300 mg. (Naltrexone is sold in 380 mg vials.)
Another randomized, double-blind, placebo-controlled study46 noted oral naltrexone’s “high dropout rates during treatment and poor compliance with medication ingestion.” At 8 weeks, the investigators found a 39% retention in treatment for those receiving placebo, while those receiving IM naltrexone 192 mg had a 60% retention rate and those receiving IM naltrexone 384 mg were retained in treatment at the rate of 68%. The article concludes that there is “…new evidence of the feasibility, efficacy, and tolerability of long acting antagonist treatments for opioid dependence.”46
While smoking rates have leveled off or declined in developed nations, tobacco use in the developing world continues to rise at a rate of approximately 3.4% per year.47 The US Centers for Disease Control and Prevention6 describes tobacco use as “the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide.”
Since the early 1990s, clinicians have been able to help their patients quit or to temporarily abstain from smoking by using a variety of nicotine-containing tobacco substitutes, or nicotine-replacement therapy (NRT). Most nicotine-replacement products are available over the counter and are fundamental tools for physicians helping patients taper themselves off of nicotine. The most popular are options such as the nicotine patch, nicotine gum, and nicotine inhaler. The patch which is placed on the upper body (usually the upper arm/deltoid) delivers nicotine through the skin to the bloodstream for approximately 24 hours. The treatment period may last for ≥8 weeks. The nicotine gum is a gum-like resin that delivers nicotine to the bloodstream, available in a 2-mg dose for regular smokers and a 4-mg dose for heavy smokers. The maximum number of pieces per day is 20 and treatment is recommended for 1–3 months, with a maximum of 6 months. The nicotine lozenge is a tablet that dissolves in the mouth and is available in 2-mg and 4-mg doses. The recommended dose is one lozenge every 2–3 hours for 6 weeks, with a gradual increase in intervals between lozenges over the next 6 weeks. Some prefer a nicotine inhaler that is shaped somewhat like a cigarette holder; when inhaled, it gives off nicotine vapors which help to relieve withdrawal symptoms. A nicotine nasal spray available with prescription has a quicker delivery system than most of the other NRTs. It is usually prescribed for 3-month periods, for a maximum of 6 months.
For many, these substitutes temporarily lessen the physical withdrawal symptoms of smoking cessation, along with peer support often in the form of groups and telephone helplines. However, for many, these treatments have fallen short of relieving symptoms and helping them to attain or maintain abstinence. This article reviews the clinical uses of two new medications that are currently being used for the treatment of nicotine addiction, bupropion and varenicline.
Bupropion is an atypical antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor and nicotinic antagonist. Initially researched and marketed as an antidepressant, bupropion was subsequently found to be effective for smoking cessation and in 1997 was approved by the FDA for use as a smoking cessation aid.48
Bupropion is widely reported to reduce the severity of nicotine cravings and withdrawal symptoms that accompany smoking cessation. After a seven-week treatment,49 27% of subjects who received bupropion reported that an urge to smoke was a problem, versus 56% of those who received placebo. In the same study,49 the patients taking bupropion reported fewer mood swings than the placebo group (21% vs. 32%, respectively).
Bupropion for smoking cessation treatment was originally recommended as a 7–12-week course, with the patient stopping the use of tobacco approximately 10 days into the course. However, many patients find that a longer course (possibly several months) has proven beneficial so clinicians can tailor treatment to patients’ needs as long as they continue to monitor for adverse effects. Dosing should begin at 150 mg/day given every day for the first 3 days, followed by a dose increase for most patients to the recommended usual dose of 300 mg/day. In comparison to nicotine replacement therapy, bupropion is similarly efficacious. Bupropion approximately doubles the chance of quitting smoking successfully after 3 months. One study50 demonstrated that 1 year after the treatment, the odds of sustaining smoking cessation were 1.5 times higher in the bupropion group than in the placebo group.
Varenicline is a more recently introduced medication indicated for smoking cessation. It is a partial agonist of the α4β2 subtype of the nicotinic acetylcholine receptor that was approved for the treatment of smoking cessation in May 2006 after demonstrating superior efficacy over NRT and bupropion with a minimal side-effect profile.
The FDA approved its use as a 12-week trial51 that, if proven successful, can be continued for another 12 weeks. However, if the patient is not successful at completely stopping smoking within the first 12-week period, continued use is not recommended.
In early comparison studies,50,52 varenicline was more effective than other strategies in helping to reduce nicotine craving and maintain abstinence. One metanalysis study50 identified varenicline to be more effective in reducing craving to both placebo and bupropion and in indirect comparisons with NRT. Another study52 demonstrated that after 1 year, the rate of continuous abstinence was 10% for placebo, 15% for bupropion, and 23% for varenicline. Varenicline has not been tested in children, those <18 years of age, or pregnant or breastfeeding women, and, therefore, is not recommended for use by these populations.
The side effects that are most commonly reported are nausea, headache, insomnia, and abnormal dreams. However, in late 2007 the FDA reported receiving several post-marketing reports of patients experiencing more serious symptoms such as suicidal ideation, erratic and suicidal behavior, and extreme drowsiness.
In early 2008 the FDA issued an alert7 to further clarify its findings, noting that “it appears increasingly likely that there is an association between varenicline and serious neuropsychiatric symptoms.” In spite of this, many patients have reported success with the medication and may decide with their physician that the short- and long-term health risks of smoking outweigh the possible dangers of a trial of this smoking cessation therapy.53 As with all new medications, clinicians are recommended to exercise caution in the use of varenicline and consider the use of alternative approaches to smoking cessation while more research is being conducted to further understand the short- and long-term risks associated with the medication.
Stimulant and cocaine dependence continue to present a major health and societal concern despite increasing public awareness of the dangers that accompany illicit drug use. According to a SAMHSA report54 in 2006, “the demand for treatment for cocaine dependence remained roughly level from 1992–2005, while the demand for treatment for amphetamine dependence increased about eight-fold.” As a result, the National Institute on Drug Abuse has pushed the scientific research community to develop treatments aimed at combating the craving, addiction, and overdose of the drug. To date, however, no treatment has been approved by the FDA.
Cognitive-behavioral therapy, motivational therapy, contingency management, and group therapy (such as 12-step programs) are behavioral therapies empirically proven to be effective in treating cocaine addiction.55-57 However, these treatments could be significantly augmented by pharmacotherapeutic agents to help patients attain initial abstinence or prevent relapse. Medications that ease the symptomatology of cocaine withdrawal (often characterized by anxiety, depression, and fatigue) are options currently available to clinicians, but they still fall far short of treating the greater problem.
Previous articles58,59 have outlined the clinical applications of the antidepressant desipramine and the anti-epileptic carbamazepine for minimizing craving for cocaine. These, however, along with several other antidepressants such as citalopram,60 bupropion,61,62 and fluoxetine,63 have shown insufficient results in treating those with cocaine dependence.
Recently, numerous medications have been shown in placebo-controlled, double-blind, randomized-controlled trials to significantly decrease cocaine dependence (BH Herman, PhD, A Elkashef, MD, and F Vocci PhD, personal communication, July 29, 2008). The focus has mostly been on substitution with stimulant medications to decrease cocaine use by inhibiting craving, reducing withdrawal, and producing tolerance to the acute reinforcing effects of cocaine.
Modafinil and propanolol have demonstrated their potential to attain abstinence by minimizing withdrawal symptoms and reducing cocaine reinforcement.64-67 Other prospective agents minimize relapse by reducing cocaine-induced euphoria and cue-induced craving. These include disulfiram68 and several gamma-aminobutyric acid (GABA)-ergic agents like baclofen,69 tiagabine,70 gamma-vinyl GABA,71 and topiramate.72
A novel approach being studied for relapse prevention is the development of a cocaine vaccine that has been shown to produce cocaine-specific antibodies that bind the drug and prevent it from crossing the blood-brain barrier.73 Similarly, another alternative method being studied is a CNS immunopharmacotherapy for the treatment of cocaine addiction. Intranasal administration of an engineered bacteriophage with cocaine sequestering antibodies on its surface is proposed to bind cocaine in the CNS and block its behavioral effects.74
The pursuit for medications to treat amphetamine and methamphetamine dependence has only recently begun. Thus, fewer medications have been tested and none approved. However, the similarities between the actions of amphetamines and those of cocaine in the brain suggest that the same medications may help with both addictions.75 As a result, studies are underway to examine many of the above proposed treatments for amphetamine and methamphetamine dependence.
The Prometa program is a heavily advertised75,76 proprietary program for the treatment of alcohol and stimulant dependence, which, according to promotional materials “…integrates physiological, nutritional, and psychosocial therapies, designed to help patients meet their individual recovery goals….”77 Although the actual medications used in the treatment are not mentioned in the promotional materials, one article78 describes the off-label use of flumazenil, hydralazine, and gabapentin in an open-label study of 50 methamphetamine addicts. During the 12-week, open-label, single-group study, the subjects received, for 3 consecutive days, hydoxyzine 50 mg, followed by flumazenil .1–.3 mg, followed by gabapentin 300 mg/day up to 1,500 mg/day, as tolerated. On days 21 and 22 of the study, the subjects were given “booster” injections of flumazenil. Among the patients treated in this study, there was a 47% reduction in self-reported use over 84 days of treatment as well as significant reductions in urine toxicology results and self-reported craving. However, since no randomized, placebo-controlled studies have been published in the peer-reviewed literature, there is no acceptable evidence that the Prometa program’s risk and expense are justified by its benefits.
Many new medications offer efficacious and effective clinical options to the general physician. The next generation of treatments (including vaccines and “cocktails”) in the pipeline also show exciting potential for further relieving these complex conditions. However, medication management alone remains limited. Comprehensive treatment of substance use disorders can only be maximized by a full biopsychosocial plan which mutually reinforces medication compliance, more traditional psychotherapy, and peer-led help groups. PP
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