1 

U.S. Department of Justice 

Drug Enforcement Administration

Schedules of Controlled Substances: Placement of Ezogabine into Schedule V 

Background, Data, and Analysis: 

Eight Factors Determinative of Control 

and Findings Pursuant to 21 U.S.C. 812(b) 

Prepared by 

Office of Diversion Control, Drug and Chemical Evaluation Section 

Washington, D.C. 20537 

September 2011

 
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I. Background 

Ezogabine (N-[2-amino-4-(4-fluorobenzylamino)-phenyl]-carbamic acid ethyl ester) is a 

new chemical substance with central nervous system depressant properties. A New Drug 

Application (NDA) for ezogabine was recently approved by the Food and Drug Administration 

(FDA) as an adjunct treatment of partial onset seizure. Ezogabine primarily acts as a ligand at 

ion-gated channels in the brain to enhance potassium currents mediated by neuronal KCNQ 

(Kv7) channels. Additionally, ezogabine indirectly enhances the gamma-aminobutyric acid 

(GABA) mediated neurotransmission. 

On January 25, 2011, the Department of Human Health Service (HHS) provided to the 

Drug Enforcement Administration (DEA) a scientific and medical evaluation entitled “Basis for 

the Recommendation to Control of Ezogabine in Schedule V of the Controlled Substances Act” 

and a scheduling recommendation. Following consideration of the eight factors and findings 

related to the substance’s abuse potential, legitimate medical use, and dependence liability, HHS 

recommended that ezogabine be controlled in Schedule V of the Controlled Substances Act 

(CSA) under 21 U.S.C. 812(b). 

The CSA requires DEA, as delegated by the Attorney General,1

 to determine whether HHS’s 

scientific and medical evaluation and all other relevant data constitute substantial evidence of 

potential for abuse such that the substance should be scheduled. 21 U.S.C. 811(b). 

 

 

1

 28 CFR 0.100(b) 
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II. Eight Factors Determinative of Control 

Pursuant to 21 U.S.C. 811(c), DEA must consider eight factors in making any finding of 

substantial evidence of potential for abuse, including the data and law enforcement information 

relevant thereto. 

Factor 1: Ezogabine's Actual or Relative Potential for Abuse 

In addition to the information HHS provided in its scientific and medical evaluation 

document for ezogabine, DEA considers all other relevant data regarding ezogabine’s actual or 

relative potential for abuse. Since ezogabine is a new chemical entity and has not been marketed 

in the United States or in any other country, information on actual abuse of ezogabine is not 

available. However, the legislative history of the CSA suggests using the following criterion in 

determining whether a particular drug or substance has a potential for abuse: 

The drug or drugs containing such a substance are new drugs so related in their action to 

a drug or drugs already listed as having a potential for abuse to make it likely that the 

drug will have the same potentiality for abuse as such drugs, thus making it reasonable to 

assume that there may be significant diversions from legitimate channels, significant use 

contrary to or without medical advice, or that it has a substantial capability of creating 

hazards to the health of the user or to the safety of the community.2

According to HHS, ezogabine, similar to pregabalin (Schedule V) and lacosamide 

(Schedule V), acts like a ligand at ion-gated channels in the brain and produces behavioral 

effects in animals and humans. Also similar to pregabalin and lacosamide, ezogabine will be 

used for the treatment of epileptic conditions in humans. Thus, it is very likely that ezogabine 

will have an abuse potential that is similar to that of Schedule V substances such as pregabalin 

and lacosamide. 

In animal studies referenced by the HHS review, ezogabine produced a sedative 

behavioral profile, including increased ataxia and decreased muscle tone and locomotion, similar 

to that generated by pregabalin and lacosamide. Studies from Phase 1 clinical trials indicated 

that the rate of euphoria-related adverse events (AE) resulting from ezogabine administration 

was 6 – 9%, which is similar to the corresponding rates resulting from pregabalin (10%) and 

lacosamide (>7%). The rate of euphoria-related AEs in Phase 2/3 studies was also similar 

between ezogabine (<1%) and lacosamide (<2%). Like other Schedule V sedative-hypnotics 

such as pregabalin and lacosamide, ezogabine produces euphoria-like effects as well as 

somnolence and abnormal feeling and thinking. In abuse potential studies with sedativehypnotic abusers, ezogabine, pregabalin and lacosamide are similar in their ability to produce 

statistically significant increases in subjective responses including “Drug Liking,” “Overall Drug 

Liking,” “Good Drug Effects,” and “High.” 

Due to its commercial unavailability in any country, there is a lack of evidence to date 

regarding ezogabine’s diversion, illicit manufacturing, or deliberate misuse or abuse. However, 

 

2

 Comprehensive Drug Abuse Prevention and Control Act of 1970, H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 

(1970); 1970 U.S.C.C.A.N. 4566, 4601. 
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since ezogabine is not readily synthesized from available substances, its diversion will 

potentially be from legitimate channels. 

In summary, the significant euphoric effects produced by ezogabine in humans predict 

that there would be significant abuse potential when ezogabine is commercially available, and 

the overall abuse potential of ezogabine is most similar to the Schedule V drugs pregabalin and 

lacosamide. 

Factor 2: Scientific Evidence of Ezogabine's Pharmacological Effects 

Neurophysiology studies showed that ezogabine acts to enhance potassium currents 

mediated by neuronal KCNQ (Kv7) channels with a secondary action through the augmentation 

of GABA-mediated neurotransmission without direct GABA receptor stimulation. The receptor 

binding studies on ezogabine did not show a significant profile of central nervous system binding 

sites associated with abuse potential including acetylcholine, dopamine, GABA, glutamate, 

glycine, histamine, opioid, serotonin, and norepinephrine receptors. Other ion channels 

including calcium, chloride, potassium, and sodium channels are not binding sites for ezogabine. 

Pre-clinical Behavioral Studies 

According to the HHS review, in preclinical studies in rats and monkeys, ezogabine, 

similar to a central nervous system depressant, reduced locomotor behavior and muscle tone, 

while increased doses of ezogabine produced seizure and death. This behavioral profile in 

animals is similar to that reported for Schedule V drugs pregabalin and lacosamide. In rats 

trained to self-administer the stimulant cocaine (Schedule II), the substitution of ezogabine did 

not maintain self-administration. Instead, the rate of self-administration by ezogabine was 

equivalent to that produced by saline. 

Human Behavioral Studies 

According to the HHS review, the abuse potential studies in individuals with histories of 

recreational sedative-hypnotic drug abuse indicate that ezogabine (300 and 600 mg orally) 

produced an increased rating on positive primary subjective scales (VAS-Drug Liking, VASOverall Drug Liking, ARCI-MBG [Euphoria], VAS-Take Drug Again) for peak responses that 

were significantly different from the placebo. This effect is similar to that produced by 

alprazolam (1.5 and 3.0 mg orally; Schedule IV). On secondary positive subjective scales (VASHigh, VAS-Good Effects, ARCI-Amphetamine [Activation]) for peak responses, both ezogabine 

and alprazolam produced significant increases compared to the placebo, while there were no 

differences between ezogabine and alprazolam on those measures. The HHS review document 

further concluded that the ratings on each of the positive subjective responses in human abuse 

potential studies conducted with ezogabine, pregabalin and lacosamide, were very similar to 

those produced by the Schedule IV benzodiazepine (alprazolam or diazepam) positive control. 

Although this appears to suggest that ezogabine, pregabalin, and lacosamide have an abuse 

potential similar to that of Schedule IV substances, the adverse effect profile data from safety, 

efficacy, and preclinical animal behavioral studies collected from ezogabine, pregabalin, and 
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lacosamide demonstrate that these three drugs have less abuse potential than Schedule IV drugs. 

These are described below. 

As referenced in the HHS review, the negative and sedating subjective measures (VASBad Effects, ARCI-LSD [dysphoria] and ARCI-PCAG [sedation]) produced by oral 

administration of ezogabine (300 and 600 mg) increased significantly compared to the placebo, 

but lower than those produced by alprazolam. Data from negative subjective scales in human 

abuse potential studies conducted with lacosamide also produced responses that were 

significantly different from alprazolam. These data from negative subjective scales suggests that 

ezogabine is more like a Schedule V drug and less like a Schedule IV drug. A higher dose of 

ezogabine (900 mg) produced ratings on VAS-Drug-liking and VAS-Good Effects that were 

higher than those reported for the two lower doses of ezogabine (300 and 600 mg) and either 

dose of alprazolam (1.5 and 3.0 mg). The values for VAS-Bad Effects and ARCI-LSD 

(dysphoria) from the 900 mg dose were less than or similar to those reported for the lower doses 

of ezogabine (300 and 600 mg) and either dose of alprazolam (1.5 and 3.0 mg). Besides several 

cardiac events, the high dose of ezogabine (900 mg) caused multiple abnormal neuro-cognitive 

effects including euphoria, somnolence, hallucination, visual disturbance, amnesia, 

hypoaesthesia, paranoia, fear, and confusion, similar to those effects observed with the Schedule 

V drug lacosamide. 

According to the HHS review, studies on Phase 1 from the Integrated Clinical 

Pharmacology (ICP) Analysis Set (n = 468 healthy subjects) showed that oral doses of ezogabine 

resulted in adverse events related to abuse potential ranging from 200 mg to 1650 mg, while in 

Phase 2/3 studies (n = 1365 patients) those doses ranged from 300 mg to 1200 mg. The 

incidence of abuse-related AEs was much higher in Phase 1 studies with healthy subjects 

compared to Phase 2/3 trials with patients. Specifically, the healthy subjects taking ezogabine in 

the Phase 1 studies had a higher rate (5.5 – 8.5%) of “euphoria,” “feeling drunk,” and “confusion 

state,” accompanied by a lower rate (1.5 -1.7%) for “disorientation,” “hallucination,” and 

“feeling abnormal.” The high rate for “somnolence” (13.4%) in the Phase 1 studies is similar to 

the rate of this AE produced by placebo (11.9%) in the Phase 2/3 Pivotal Clinical Trial (PCT) 

studies. The Phase 2/3 trial data suggests that patients who were taking ezogabine in 

combination with other anti-epileptic and CNS-active drugs showed a relatively low rate of 

“euphoria” (0.4-0.5%), but a higher rate for “feeling drunk” (0.9 – 1.5%) compared to the 

placebo (none for both AEs). In this group, the rate of “disorientation” (1.7 – 2.1% compared to 

0.7% from placebo) was similar to that seen in the Phase 1 studies, although the rate of 

“hallucination” (1.0 – 1.1% compared to 0% from placebo) and “feeling abnormal” (0. 1 – 0.3% 

compared to 0% from placebo) were lower than those observed in the Phase 1 trials. However, 

there was a much higher rate of “somnolence” in Phase 2/3 studies (22 - 28.5% compared to 

11.9% from placebo) compared to the rate in Phase 1 studies. This fact is similar to the clinical 

study data in the NDAs for Schedule V drugs pregabalin and lacosamide. Pregabalin and 

lacosamide produced additional abused-related AEs similar to those from ezogabine, including 

somnolence, abnormal feeling and thinking, and dizziness. 

In another Phase 1 trial, the incidence of AEs related to abuse potential was observed 

following administration of a placebo, ezogabine, and alprazolam. Both doses of alprazolam 

(1.5 and 3.0 mg) and the highest dose of ezogabine (900 mg) produced the highest levels of 
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somnolence (57%, 97% and 67%, respectively), compared to the placebo (15%). The 3.0 mg 

dose of alprazolam and all three doses of ezogabine (300, 600 and 900 mg) also produce higher 

levels of euphoria (17%, 18%, 21% and 33%, respectively), compared to the placebo (8%). In 

general, doses of ezogabine above 400 mg produced the greatest number of abuse-related AEs 

and the 900 mg dose of ezogabine was terminated from the protocol following serious cardiac 

effects. This trend is very similar to the clinical data in the NDA for the Schedule V drug 

lacosamide. 

In summary, the abuse-related AEs produced by ezogabine are similar to those indicated 

in the NDA for the human abuse potential study conducted with lacosamide. 

Factor 3: The State of Current Scientific Knowledge Regarding Ezogabine 

As stated in the HHS review document, the chemical name of ezogabine is N-[2-amino4-(4-fluorobenzylamino)-phenyl]-carbamic acid ethyl ester. It is an achiral molecule with a 

molecular formula of C16H18FN3O2 and a molecular weight of 303.3 g/mol. Ezogabine is a nonhygroscopic white to slightly colored powder with a melting point of 140-143 0

C. It is soluble in 

0.9% saline, methanol, and chloroform, but only sparingly soluble in ethanol and 0.1N HCL. 

According to the HHS review, ezogabine in humans has a Tmax (Time required for 

ezogabine to reach maximum plasma concentration) ranging from 1-4 hours following both acute 

and multiple dosing. Without the involvement of cytochrome P450, ezogabine undergoes 

extensively and exclusively a phase 2 metabolic biotransformation. Ezogabine is predominantly 

metabolized by N-glucuronidation resulting in the formation of two distinct N-glucuronides of 

the unchanged parent drug and to a lesser extent by N-acetylation to form N-acetyl-retigabine, 

the major bioactive metabolite of ezogabine. The half-life of both ezogabine and N-acetylretigabine is around eight hours and the Cmax (maximum plasma concentration) of both 

components is dose proportional after both acute and multiple dosing, suggesting a lack of 

accumulation with repeated administration. The oral administration of ezogabine produces an 

absolute bioavailability of approximately 60%. Ezogabine is excreted majorly by the renal route 

and using radio-labeled ezogabine it was found that a total of 84% of the administrated dose of 

ezogabine was recovered in the urine either as unchanged parent drug, N-glucuronides of the 

parent drug and the acetyl metabolite, or the mono-acetyl metabolite. 

 

Factor 4: Ezogabine's History and Current Pattern of Abuse 

According to the HHS review, the information on ezogabine's history and current pattern 

of abuse is unavailable since it has not been marketed in any country. Thus, the evaluation of 

abuse potential of ezogabine derives from positive indictors in pre-market clinical trials which 

are believed to be predictive of drug abuse. As stated in previous sections, in human abuse 

potential study, ezogabine (300 and 600 mg) produced increased rating on positive subjective 

scales higher than that of placebo, but similar to that produced by alprazolam (1.5 and 3.0 mg, 

Schedule IV). The negative and sedating subjective measures produced by ezogabine (300 and 

600 mg) increased significantly compared to the placebo, but lower than those produced by 

alprazolam (Schedule IV). These data are similar to that reported in previously conducted 

human abuse potential studies with Schedule V drugs such as pregabalin and lacosamide. In that 
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study, abuse-related AE events included euphoric mood, dizziness, memory impairment, anxiety, 

and disturbed attention. These AEs are similar to those described in the NDA for the human 

abuse potential study conducted with lacosamide. The 900 mg dose of ezogabine caused serious 

adverse cardiac events that suggest that if ezogabine was misused or abused at this dose or 

above, it could pose serious safety risks. 

As stated in the HHS review, in clinical safety and efficacy studies, ezogabine produced a 

high incidence of abuse-related AEs such as euphoria, hallucinations, cognitive changes, and 

somnolence. The incidence of these AEs was higher in Phase 1 studies with healthy individuals 

than in Phase 2/3 studies in patients with seizure disorders who were also on antiepileptic and 

psychoactive medications. This differential incidence of AEs following ezogabine in Phase 1 

versus Phase 2/3 studies is similar to the clinical study data mentioned in the NDAs for 

pregabalin and lacosamide in which the somnolence, abnormal thinking and dizziness were the 

most frequently observed. 

Factor 5: The Scope, Duration, and Significance of Abuse of Ezogabine 

An assessment of the scope, duration, and significance of ezogabine abuse is not 

available since it has not been marketed in any country. However, as stated in the HHS review, 

the epidemiological data on pregabalin, a Schedule V drug with an abuse potential similar to that 

of ezogabine, are available from Drug Abuse Warning Network (DAWN) database. DAWN is a 

public health surveillance system that monitors drug-related visits to hospital emergency 

departments (EDs). This data is reported to DAWN by a sample of participating general, nonFederal hospitals with operating 24-hour EDs. DAWN provides information on all drug-related 

ED visits, regardless of the motive for using the drug. DAWN captures data on all drugs such as 

illicit drugs, prescription and over-the-counter pharmaceuticals, dietary supplements, nonpharmaceutical inhalants, alcohol when it is combined with other drugs, and, for patients under 

age 21, ED visits where alcohol is the only substance. 

HHS used the non-medical use of a drug, one of the measures reported by DAWN, and 

the prescription data collected from the SDI Vector OneTM database to estimate the “abuse 

frequency ratio” as a relative measure for abuse potential of a drug. HHS found that the “abuse 

frequency ratio” for pregbalin, calculated as the ratio of nonmedical use related annual ED visits 

(as reported in DAWN) to the total number of annual prescriptions, is less than that for 

alprazolam. The “abuse frequency ratio” for pregabalin ranges from 29 to 47, while those for 

alprazolam are about 3-6 times higher, ranging from 160 to 235. Thus, the epidemiological data 

show that placement of pregabalin into Schedule V based on abuse-related human and animal 

data submitted in its NDA justifies its placement relative to drugs in Schedule IV. Given that 

ezogabine has similar abuse-related human and animal data in its NDA to the data generated by 

pregabalin, it is likely that ezogabine will have an abuse potential similar to this Schedule V 

drug. 

Beyond epidemiological data, ezogabine and Schedule V drugs such as pregabalin and 

lacosamide produced positive subjective effects in a human abuse potential study that are similar 

to those produced by Schedule IV benzodiazepines (diazepam or alprazolam). In a HHS-cited 

study, recreational sedative-hypnotic abusers receiving single doses of ezogabine (300, 600, 900 
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mg) reported incidences of euphoria-type AEs at a rate which was significantly higher than that 

reported for the placebo, but indistinguishable from that produced by 1.5 or 3.0 mg alprazolam. 

In this population, euphoric mood following single doses of 300, 600 and 900 mg ezogabine 

occurred in 18%, 21%, and 33% of subjects respectively, as compared to 8% following a 

placebo. The high dose (900 mg) of ezogabine, but not the placebo, produced hallucinations. In 

another human abuse potential study, lacosamide produced euphoria as an adverse event (15%) 

following a single oral dose of 800 mg, as compared to none following placebo administration. 

Similarly, in individuals with a history of recreational abuse of sedative-hypnotic drugs, 450 mg 

pregabalin received high ratings of “Good Drug Effect,” “High,” and “Liking” that was similar 

to a single dose of 30 mg diazepam. 

In Phase 2/3 clinical studies in patients with partial seizures, 300 to 1200 mg doses of 

ezogabine produced euphoric mood in 0.5% and feeling drunk in 1.5% of the subjects as 

compared to none in placebo-treated condition. Similarly, the rate of euphoria as an AE 

following ezogabine was comparable to the corresponding rates of euphoria following 

therapeutic doses of lacosamide (less than 1%). Pregabalin, in controlled clinical studies 

involving 5500 patients, produced euphoria in 4% of the subjects compared to 1% in placebo 

condition. Thus, despite some similarities between ezogabine and alprazolam, the overall abuse 

potential of ezogabine is more similar to the Schedule V drugs pregabalin and lacosamide. 

Factor 6: What, If Any, Risk to the Public Health 

Based on the review of clinical data, HHS concluded that the abuse of ezogabine is likely 

to pose a similar risk to public health as that of Schedule V substances, pregabalin and 

lacosamide. In Phase 1 clinical safety studies, the rate of euphoria-related AEs following 

ezogabine administration was about 6-9%, which is similar to that from pregabalin (10%) and 

lacosamide (>7%). The overall AE profiles following ezogabine, pregabalin, and lacosamide 

include not only euphoria, but also somnolence and feeling or thinking abnormally. 

The human abuse potential study with histories of recreational abuse of sedativehypnotics showed that the majority of subjects receiving the 900 mg dose of ezogabine 

experienced multiple AEs such as euphoria, somnolence, visual disturbance, amnesia, 

hypoaesthesia, paranoia, fear, confusion, and hallucinations. Although the 900 mg dose is three 

times greater than the recommended therapeutic dose, drug abusers typically use supratherapeutic doses. Thus, this data indicates that ezogabine may present a serious health risk to 

the public, with a predicted level of risk similar to that observed with pregabalin and lacosamide. 

Following ingestion of supra-therapeutic doses, pregabalin caused euphoria, somnolence, 

hallucination, asthenia, headache, and dizziness, while lacosamide ingestion produced euphoric 

mood, somnolence, sensory motor impairment, and deficit in information processing. 

In summary, the available study’s data indicate that ezogabine may present risks to the 

public health at a level similar to those produced by the Schedule V drugs pregabalin and 

lacosamide, but are less than those produced by Schedule IV benzodiazepines. 
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Factor 7: Ezogabine's Psychic or Physiological Dependence Liability 

The HHS review document states that studies of abrupt discontinuation of ezogabine 

were not conducted and there are minimal data available to evaluate the ability of ezogabine to 

induce withdrawal syndromes that are indicative of physical dependence. However, many AEs 

reported from the discontinuation of ezogabine were also reported prior to the discontinuation 

including dizziness, somnolence, and a confusion state. Abrupt discontinuation of pregabalin in 

human studies resulted in patient-reported symptoms of nausea, headache,or diarrhea, which are 

suggestive of physical dependence. Abrupt discontinuation of lacosamide in clinical trials with 

diabetic neuropathic pain patients produced no signs or symptoms. 

As cited by the HHS review, the ability of ezogabine to produce psychic dependence is 

suggested by AE reports of euphoric mood in sedative-hypnotic abusers in the human abuse 

potential study (18-33%) and in healthy individuals (8.5%) in clinical Phase 1 studies. Unlike 

ezogabine and pregabalin, the withdrawal syndrome following discontinuation of other Schedule 

IV substances such as alprazolam can range from mild dysphoria and insomnia to a major 

syndrome including abdominal pain, muscle cramps, vomiting, sweating, tremors, and 

convulsions. These are similar in character to those associated with other sedative-hypnotics. 

The withdrawal symptoms following abrupt termination of diazepam (Schedule IV) have been 

reported to include tremor, abdominal and muscle cramps, vomiting, sweating, headache, muscle 

pain, extreme anxiety, tension, restlessness, confusion, and irritability. In severe cases, 

especially in those patients who had received excessive doses over an extended period of time, 

the symptoms may include derealization, depersonalization, hyperacusis, numbness and tingling 

of the extremities, hypersensitivity to light, noise, and physical contact, and hallucinations or 

epileptic seizures. 

The HHS review document concludes that the AEs relevant to ezogabine’s psychic and 

physiological dependence liability appear to be less severe and occur less frequently than those 

of Schedule IV benzodiazepines (diazepam and alprazolam) and are more similar to those of 

Schedule V substances like pregabalin and lacosamide. Thus, ezogabine produces limited 

psychic or physiological dependence liability following extended administration and it is likely 

to be similar to those of pregabalin and lacosamide. 

Factor 8: Whether Ezogabine Is an Immediate Precursor of a Substance Already 

Controlled 

Ezogabine is not an immediate precursor of a substance already controlled. 

References 

1. Department of Health and Human Services (HHS) Review (2011): Basis for the 

Recommendation for Control of Ezogabine in Schedule V of the Controlled Substances 

Act. 

 
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III. Findings for Schedule Placement Pursuant to 21 U.S.C. 812(b) 

21 U.S.C. 812(b) requires the evaluation of a substance’s abuse potential, accepted 

medical use, and safety for use under medical supervision for scheduling under the CSA as a 

controlled substance. After consideration of the above eight factors determinative of control of a 

substance (21 U.S.C. 811(c)), and a review of the scientific and medical evaluation and 

scheduling recommendation provided by HHS, DEA finds that ezogabine meets the following 

criteria for placement in Schedule V of the CSA pursuant to 21 U.S.C. 812 (b)(5). 

1)		Ezogabine has a low potential for abuse relative to the drugs or other substances

in Schedule IV.

The collected information suggests that the abuse potential of ezogabine is less than that 

of Schedule IV drugs and is similar to that of Schedule V drugs such as pregabalin and 

lacosamide. Ezogabine, pregabalin, and lacosamide, all produce positive subjective effects in 

human abuse potential studies and those effects are similar to those produced by Schedule IV 

benzodiazepines (diazepam or alprazolam). Ezogabine, pregabalin, and lacosamide also produce 

high rates of euphoria and other abuse-related adverse effects in Phase 1 studies with healthy 

individuals. However, the effects produced by ezogabine, pregabalin and lacosamide differ from 

diazepam or alprazolam in the negative subjective response profile, pharmacokinetics, cognitive 

impairment, and withdrawal syndromes following drug discontinuation. Thus, despite some 

similarities between ezogabine and alprazolam (Schedule IV), the overall abuse potential of 

ezogabine is most similar to that of the Schedule V drugs pregabalin and lacosamide. 

2)		Ezogabine has a currently accepted medical use in the United States.

Ezogabine (Potiga®) was recently approved by FDA as an adjunct treatment of partial 

onset seizures and has a currently accepted medical use in the United States. 

3) Abuse of Ezogabine may lead to limited physical dependence or psychological 

dependence relative to the drugs or other substances in Schedule IV. 

Ezogabine may produce limited physical and psychological dependence relative to drugs 

in Schedule IV. Physical dependence was not fully assessed because abrupt discontinuation of 

ezogabine was not studied in subjects following extended administration. Psychological 

dependence is suggested by the ability of ezogabine to produce positive subjective response 

(euphoria) in participants of clinical studies. This is similar to Schedule V substances such as 

pregabalin and lacosamide. 

REFERENCES 

1. Department of Health and Human Services Review (2011): Basis for the 

Recommendation for Control of Ezogabine in Schedule V of the Controlled Substances 

Act.