No abstract

Despite modest effects of gabapentin overuse alone, overuse of gabapentin with opioids may increase risk of harm and health-service utilization, supporting calls to make gabapentin a controlled substance in the USA.

Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses.

Upward trends in ADHD diagnosis and treatment have continued but vary markedly by group. Studies of undertreatment/overtreatment are needed.

The abuse potential of gabapentin is well documented; with gabapentin having been noted as an agent highly sought after for use in potentiating opioids. When combined with opioids, the risk of respiratory depression and opioid-related mortality increases significantly. In the US, gabapentin was approved by the Food and Drug Administration as a non-controlled substance. To date, and in spite of empirical evidence suggestive of diversion and abuse with opioids, gabapentin remains a non-controlled substance at the federal level. This has forced individual US states and jurisdictions – often significantly impacted by the opioid epidemic – to forge ahead with legislative initiatives designed to reclassify and/or monitor the use of gabapentin. Since August 1, 2016, 14 of 51 US states and jurisdictions have either implemented legislative mandates requiring pharmacovigilance programs, amended rules and regulations, are in the throes of crafting policy, or are in the midst of gathering additional data for decision making. This fragmented geographic approach yields only a modest benefit in combating the abuse of gabapentin and/or the national opioid epidemic. Herein, we report state-by-state efforts to enhance pharmacovigilance and call for a re-evaluation of the schedule status of gabapentin at the federal level, and design and implementation of a national pharmacovigilance program.

No abstract

Low dose buprenorphine initiation, is an alternative method of initiating buprenorphine in which the starting dose is very low and gradually increased to therapeutic levels over a period of days. This method takes advantage of slow displacement of the full opioid agonist from mu-opioid receptors, avoiding the need for a person with opioid use disorder to experience opioid withdrawal symptoms before initiating buprenorphine, while also minimizing the risk of precipitated opioid withdrawal. With this initiation method, full opioid agonists can be continued as buprenorphine is initiated, expanding the population to which buprenorphine can be offered. To date, the literature on low dose initiation is primarily case-based but rapidly growing. While evidence emerges, guidance for the use of low dose initiation is clearly desired and urgently needed in the context of an increasingly risky and contaminated opioid drug supply, particularly with high potency synthetic opioids, driving overdose deaths. Despite limited evidence, several principles to guide low dose initiation have been identified including: (1) choosing the appropriate clinical situation, (2) initiating at a low buprenorphine dose, (3) titrating the buprenorphine dose gradually, (4) continuing the full opioid agonist even if it is nonmedical, (5) communicating clearly with frequent monitoring, (6) pausing or delaying buprenorphine dose changes if opioid withdrawal symptoms occur, and (7) prioritizing care coordination. We review a practical approach to low dose initiation in hospital-based and outpatient settings guided by the current evidence.

This article will review the epidemiology and pharmacology of gabapentinoids (gabapentin and pregabalin) relevant to their emerging misuse potential and provide guidance for clinical and regulatory management. Gabapentinoids are γ‐aminobutyric acid analogues that produce their therapeutic effects by inhibiting voltage‐gated calcium channels and decreasing neurotransmitter release. Recently gabapentinoid prescribing and use have increased tremendously. Although traditionally thought to possess a favorable safety profile, gabapentinoid misuse has also risen significantly. Gabapentinoid misuse generally occurs in combination with other substances, most notably opioids, and may be for purposes of eliciting euphoric effects, enhancing the effects of other substances, or self‐treating conditions such as withdrawal, pain, anxiety, or insomnia. Given its faster onset, increased bioavailability and potency, and nonsaturable absorption, pregabalin's pharmacokinetics theoretically enhance its misuse liability versus gabapentin. However, gabapentin can produce similar euphoric effects, and epidemiologic studies have identified higher rates of gabapentin misuse in the United States, likely because of greater availability and less regulated prescribing. Although adverse events of gabapentinoid‐only ingestion are relatively benign, a growing body of evidence indicates that gabapentinoids significantly increase opioid‐related morbidity and mortality when used concomitantly. In addition, significant withdrawal effects may occur on abrupt discontinuation. As a result of these trends, several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug‐monitoring programs. Although increased regulation of gabapentin prescribing may be warranted, harm reduction efforts and increased patient and provider education are necessary to mitigate this concerning gabapentinoid misuse trend.