Short-term Treatment of Cocaine and/or Methamphetamine Abuse With Vigabatrin: Ocular Safety Pilot Results

Article (PDF Available)inArchives of Ophthalmology 124(9):1257-62 · October 2006with35 Reads
DOI: 10.1001/archopht.124.9.1257 · Source: PubMed
Abstract
To evaluate the ocular safety of short-term use of vigabatrin to treat cocaine and/or methamphetamine addiction. Individuals who were actively using cocaine and/or methamphetamine were eligible for enrollment. Enrolled subjects were scheduled for comprehensive eye examinations at the beginning and end of the study. Visual field testing was performed at baseline and 1 week, 4 weeks, 8 weeks, and 1 month or more after discontinuing vigabatrin. Twenty-eight subjects received at least 1 dose of vigabatrin; however, only 20 subjects continued beyond the initial escalating vigabatrin dose phase to the treatment phase. Of these 20 subjects, 18 completed the study with full follow-up. Visual fields were evaluated subjectively by 2 glaucoma specialists and analyzed objectively for group and individual changes in quadrant mean sensitivity. The objective analysis was also repeated for superior field quadrants after excluding the uppermost peripheral points to minimize the eyelid effect. The main outcome measures were change of visual field, visual acuity, and ocular adverse effects. Vigabatrin seemed to help treat cocaine and/or methamphetamine addiction. Of 18 subjects, 16 had negative test results for cocaine and methamphetamine use during the last 6 weeks of the trial. No ocular adverse events were detected. The subjective evaluation did not reveal visual field constriction in any of the 18 evaluable participants. Objective group and individual analyses for quadrant mean sensitivity did not show any change from baseline in any quadrant. No changes in visual acuity were noted. In this short-term pilot study, vigabatrin seemed to help treat cocaine and/or methamphetamine abuse. There was no evidence of ocular or visual field adverse effects.

Figures

CLINICAL SCIENCES
Short-term Treatment of Cocaine
and/or Methamphetamine Abuse With Vigabatrin
Ocular Safety Pilot Results
Robert D. Fechtner, MD; Albert S. Khouri, MD; Emilia Figueroa, MD; Marina Ramirez, MD;
Martha Federico, LSW; Stephen L. Dewey, PhD; Jonathan D. Brodie, MD, PhD
Objective: To evaluate the ocular safety of short-term
use of vigabatrin to treat cocaine and/or methamphet-
amine addiction.
Methods: Individuals who were actively using cocaine
and/or methamphetamine were eligible for enrollment.
Enrolled subjects were scheduled for comprehensive eye
examinations at the beginning and end of the study. Vi-
sual field testing was performed at baseline and 1 week,
4 weeks, 8 weeks, and 1 month or more after discon-
tinuing vigabatrin. Twenty-eight subjects received at least
1 dose of vigabatrin; however, only 20 subjects contin-
ued beyond the initial escalating vigabatrin dose phase
to the treatment phase. Of these 20 subjects, 18 com-
pleted the study with full follow-up. Visual fields were
evaluated subjectively by 2 glaucoma specialists and ana-
lyzed objectively for group and individual changes in
quadrant mean sensitivity. The objective analysis was also
repeated for superior field quadrants after excluding the
uppermost peripheral points to minimize the eyelid effect.
The main outcome measures were change of visual field,
visual acuity, and ocular adverse effects.
Results: Vigabatrin seemed to help treat cocaine and/or
methamphetamine addiction. Of 18 subjects, 16 had nega-
tive test results for cocaine and methamphetamine use
during the last 6 weeks of the trial. No ocular adverse
events were detected. The subjective evaluation did not
reveal visual field constriction in any of the 18 evalu-
able participants. Objective group and individual analy-
ses for quadrant mean sensitivity did not show any change
from baseline in any quadrant. No changes in visual acu-
ity were noted.
Conclusions: In this short-term pilot study, vigabatrin
seemed to help treat cocaine and/or methamphetamine
abuse. There was no evidence of ocular or visual field ad-
verse effects.
Arch Ophthalmol. 2006;124:1257-1262
T
HE CLINICAL USE OF VIGABA-
trin has been limited be-
cause of an association with
the development of visual
field defects.
1,2
Vigabatrin
(-vinyl-GABA [-vinyl--aminobutyric
acid]) is indicated for the long-term treat-
ment of epilepsy in combination with other
antiepileptic drugs, mostly for patients who
have resistant partial epilepsy with or with-
out secondary generalization (ie, vigaba-
trin is indicated where other appropriate
drug combinations have proved inad-
equate or have not been tolerated). Viga-
batrin is also used as monotherapy in the
treatment of infantile spasms.
Vigabatrin is effective, but clinicians are
reluctant to prescribe it because of the visual
field defects it can cause. The exact patho-
physiological mechanism of vigabatrin-
associatedvisual field defectsremains unclear.
Interindividual susceptibility suggests that
a possible idiosyncratic drug reaction may
underlie the pathogenesis of observed visual
field loss.
2
The observed visual field defects
in various studies tended to behave differ-
ently. Although some studies
3
suggested that
visual field loss was irreversible, a few
1,4
re-
ported an improvement in visual field loss
on discontinuation of vigabatrin. Other stud-
ies
2,5
found no correlation between treatment
durationor cumulative dosage and visual field
loss. While there are conflicting reports as
to whether emergent defects are stable
3
or re-
versible,
6
to our knowledge, there is not a
single report of progression following
vigabatrin discontinuation.
Because vigabatrin is typically used to
treat chronic conditions such as epilepsy,
long-term safety remains a concern. How-
ever, short-term use of vigabatrin has not
been well studied because of its indication
for the treatment of chronic disease.
A new and promising short-term use of
vigabatrin has recently been described.
Short-term use of vigabatrin seems to be
effective in the treatment of cocaine and/or
methamphetamine dependence.
7
In the
Author Affiliations: Institute of
Ophthalmology and Visual
Science, University of
Medicine and Dentistry of
New Jersey–New Jersey Medical
School, Newark (Drs Fechtner
and Khouri); Codet Aris Vision
Institute, Tijuana, Mexico
(Drs Figueroa and Ramirez and
Ms Federico); Department of
Psychiatry, NYU School of
Medicine, New York
(Drs Dewey and Brodie); and
Chemistry Department,
Brookhaven National
Laboratory, Upton, NY
(Dr Dewey).
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present study, 16 of 18 subjects had negative test results
for cocaine and methamphetamine abuse during the last
6 weeks. This group of subjects had a mean daily re-
ported use of nearly1gofmethamphetamine or co-
caine for 12 years, and no subject acknowledged a his-
tory of more than several consecutive days drug free in
the year preceding enrollment in the study.
Vigabatrin, an irreversible inhibitor of GABA trans-
aminase, attenuates the rapid elevation in nucleus ac-
cumbens dopamine level that characterizes the neuro-
chemical response to cocaine, methamphetamine, and
other drugs of abuse.
8,9
In contrast with its long-term use
as an antiepileptic drug, vigabatrin for drug dependence
was used for a relatively short period (9 weeks) in this
pilot study. This dosing regimen may not carry the same
risk of visual field loss as does long-term use in combi-
nation with other drugs for epilepsy.
Because long-term vigabatrin use is associated with
visual field loss, the subjects in this pilot study of viga-
batrin treatment of methamphetamine and/or cocaine de-
pendence underwent ocular safety monitoring and fre-
quent automated visual field testing. We report herein
the monitoring strategy developed and the results of the
ocular safety analysis.
METHODS
All enrolled subjects were recruited by word of mouth and
provided signed informed consent. The protocol for this study
was reviewed and approved in Mexico by the Comision Federal
para la Protecion Contra Riesgos Sanitarios (reference No.
03320100101) following review by the staff of the director de
Evaluacion de Medicamentos, according to the standards of the
Declaration of Helsinki, as currently modified. Institutional re-
view board committee approval (University of Medicine and
Dentistry of New Jersey, Newark) was obtained for the review
and analysis of all visual safety data.
Subjects who met the Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition
10
criteria for methamphet-
amine and/or cocaine dependence and who were eligible to be-
gin vigabatrin treatment provided a complete preadmission his-
tory and underwent a physical examination. Subjects underwent
a complete ophthalmic evaluation by an ophthalmologist (E.F.)
at baseline and on completion of the study. This included an
evaluation of best-corrected visual acuity (using the Snellen
chart) and slitlamp and dilated fundus examinations. Visual acu-
ity was determined before any other visual field testing at each
visit. Visual acuity was tested with best refraction.
Automated visual field testing with the Humphrey field ana-
lyzer (HFA) was performed at baseline before starting vigaba-
trin treatment. To ensure the reliability of visual field testing,
all subjects underwent at least 1 visual field test before base-
line. For training purposes, a 120° screening visual field test
was performed. Practice fields were marked as “practice” and
not used in the analysis of data.
To monitor for visual field defects, testing was performed
at baseline and then repeated after 1, 4, and 8 weeks of treat-
ment with vigabatrin. Subjects were retested 4 weeks (or more)
after cessation of vigabatrin treatment. Study fields were tested
with HFA 60-4 to test the peripheral field. Every subject had 2
sets of reliable fields at baseline for both eyes before starting
the study medication (visit 1). The 2 baseline fields were ob-
tained on the same day or on different days. To probe for the
emergence of any detectable central visual field threshold
changes, each subject also had a central field test (HFA 24-2)
performed in 1 eye (either the eye with the better best-
corrected visual acuity or, if equal, the right eye) at baseline
and again on the last exit visit.
Vigabatrin administration was initiated according to pro-
tocol at 500 mg twice daily for 3 days, then 1.5 g/d for the next
4 days and 2.0 g/d for the next week. On day 15, subjects were
given 3.0 g/d; that dose was maintained for the next 28 days.
Then, subjects were tapered off medication over the next 3
weeks. Completers received a cumulative dose of 137.0 g of vi-
gabatrin.
Once receiving treatment with vigabatrin, subjects re-
turned for follow-up at 1 week (visit 2), 4 weeks (visit 3), and
8 weeks (visit 4) of therapy. During each of those visits, best-
corrected visual acuity was measured and HFA 60-4 testing was
performed on both eyes. Visual field test results were evalu-
ated by an ophthalmologist (E.F.) at each study visit and com-
pared with the baseline fields. If a subject showed a change in
visual field at visits 2, 3, or 4, the protocol required confirma-
tion and discontinuation of the study drug.
Once treatment was completed, subjects returned for their
exit visit 1 month (longer for some) after discontinuing viga-
batrin. On their exit visit (visit 5), best-corrected visual acuity
was determined and slitlamp and dilated fundus examinations
were performed. Peripheral visual field testing (with HFA 60-4)
was performed on both eyes, and central testing (with HFA 24-2)
was performed in 1 eye (
Table 1).
Table 1. Study Flow Chart*
Procedure
Visit 1
(Baseline),
Day −30 to 0
Visit 2
(Initial),
Week 1
Visit 3
(Interim),
Week 4
Visit 4
(Final),
Week 8
Visit 5
(Follow-up),
Week 12
End Point
Testing†
Best-corrected Snellen visual acuity determination X X X X X X
Visual field determination
Peripheral (both eyes)‡ X (2 fields at
baseline)§
XXX X X
Central (1 eye) XXX
Fundus examination¶ X X X
*X denotes that the procedure was performed at that time point; no entry indicates that the procedure was not performed at that time point.
†If the Humphrey field analyzer (HFA) 60-4 test result changed, end point testing was performed.
‡The HFA 60-4 test was used.
§The HFA 120-point screening test was used if the subject had not had an HFA examination before.
The HFA 24-2 test was used on the eye with the better best-corrected visual acuity or, if the best-corrected visual acuity was equal, on the right eye.
¶Must be performed last if dilation is required.
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For this study, we had to develop an analysis algorithm for
the HFA 60-4 tests. Although there is abundant information
about assessing change in central visual field (HFA 24-2 and
30-2 tests) using threshold automated achromatic perimetry,
there is little information on and no software for performing
similar analysis in the peripheral field. The effects of cocaine
and/or methamphetamine on visual field performance are simi-
larly undefined. The study population actively abusing drugs
does not correspond to any available normative database. Nev-
ertheless, these subjects were able to provide reliable visual
fields.
To best analyze our data, we established a baseline for each
subject and then developed subjective and objective analysis
strategies. The subjective analysis was performed by 2 glau-
coma specialists (R.D.F. and A.S.K.) with experience in visual
field evaluation and pathological patterns. Each test was evalu-
ated separately for defects and reliability. Reliability criteria (fixa-
tion losses, false positives, and false negatives) below 20% were
considered indicative of adequate performance. Final visual field
test results were then compared with their respective baseline
results, and a clinical impression of clinically significant change
or no change was assigned.
The objective analysis was performed for the whole group
and for individual subjects by quadrant. For the group objec-
tive analysis, total sensitivity (sum of thresholds) per quad-
rant for right and left eyes was the unit of analysis. The quad-
rant mean sensitivity, standard deviation, and root mean square
error/mean as a measure of variability for the 2 baseline pe-
ripheral fields were calculated for both eyes. The 8 quadrant
total sensitivities at the end of the study were then compared
with the corresponding baseline totals. Because of frequent up-
per eyelid artifact, the superior field quadrants were also ana-
lyzed after adjusting the total sensitivity per quadrant by ex-
cluding the uppermost peripheral tested points most likely to
be influenced by eyelid position (
Figure).
For the individual objective analysis, the calculated quad-
rant means and standard deviations for the study population
at baseline, in each of the 8 quadrants, were used to establish
the estimated variability. Deciding on the best criteria for ob-
jective analysis was particularly challenging because of the
known inherent variability in peripheral field sensitivity
11
and
the lack of published standards for the analysis of peripheral
visual fields. A significant change was defined as any
quadrant total sensitivity in a patient that decreased by greater
than 2 SDs.
RESULTS
No subjects were excluded for ocular abnormalities. Al-
though there were high dropout rates at the screening
phase (42 subjects were screened for the study, but 14
did not return to start vigabatrin treatment), most sub-
jects who continued beyond the initial escalating dose
phase completed the study; retention was excellent in sub-
jects exposed to more than a few doses of vigabatrin. In
total, 28 subjects received at least 1 dose of vigabatrin;
however, only 20 subjects continued beyond the initial
escalating vigabatrin dose phase. Two of those subjects
were lost to follow-up. Eighteen subjects completed the
study (17 men and 1 woman; average age, 33 years), with
an exit examination at the visit 4 weeks or beyond (visit
5) following cessation of vigabatrin treatment.
No changes in visual acuity, slitlamp biomicroscopy,
or retinal examination results were noted throughout
the study. No subjects had to discontinue the study
medication during the protocol because of visual field
change. Among the 18 subjects who completed the
study, none showed a change in the central or periph-
eral field warranting cessation of the drug. In addition,
for the 28 subjects for whom at least 1 visual field while
receiving treatment was available, there were no abnor-
malities detected.
Subjective evaluation of baseline peripheral visual field
examination results showed variability, which was ex-
pected for peripheral locations and inexperienced visual
field test takers. Far peripheral defects at baseline were more
commonly present in the superior and nasal quadrants,
but did not progress during the study. Seven subjects had
fields that were unequivocally stable from baseline through
the end of the study. Eleven subjects required retesting at
study exit. These subjects most typically showed a de-
pressed sensitivity in the far superior and/or nasal visual
field region. Five had a superior-nasal peripheral depres-
sion, 5 had a superior depression only, and 1 had a nasal
depression only. All returned according to protocol to be
retested for confirmation of a possible change in their pe-
ripheral visual field. On retesting, all returned to the base-
line condition. During retesting, special attention was paid
to eliminating upper eyelid artifact and head turn (nasal)
artifact. No defects were noted on the central HFA 24-2
visual field test results at baseline or at exit.
Thus, our subjective interpretation of peripheral and
central fields yielded no change from baseline for any of
the 18 subjects.
For the study group as a whole, changes in quadrant
total sensitivities were analyzed for both eyes and showed
no significant decrease in any quadrant of either eye
(
Table 2). For superior quadrants, group objective analy-
ses were repeated after excluding the outermost supe-
23 19 0
16 25
333 218
411 219
26 26 23 27 21 29 22 <0
2830 29 29 24 10
3028 30 29 28 0
3028
60 60
30 26 22 <0
2825 30 22 19 <0
28 24 26 26 23 22 19 4
23 22 24 25 24 013 <0
22 20 14 12
<0<0<0
Figure. Illustration of the 60-4 threshold plot of the visual field analyzer
(Humphrey field analyzer) (the open triangle is part of the standard printout
and indicates the location of the optic nerve). All data points are given in
decibels. The quadrant total sensitivities used in the analysis are in ovals;
the censored superior points in the rectangular box were excluded in the
subanalysis.
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rior points. No significant changes in total sensitivity were
noted (
Table 3).
Because the group analysis would not identify indi-
viduals with visual field change, individual objective analy-
sis was also performed. None of the subjects showed a
negative change in quadrant sensitivity that exceeded 2
SDs for that specific quadrant. In fact, 3 subjects showed
an improvement in quadrant mean sensitivity of greater
than 2 SDs.
A post hoc power calculation showed that the 18 sub-
jects were enough to rule out (reject) a mean 0.5 root
mean square error decrease or worse at P.05 for all vi-
sual field quadrants.
COMMENT
The short-term use of vigabatrin seems promising for treat-
ing cocaine and methamphetamine abuse. No visual field
defects developed with short-term use in this pilot study.
No changes in acuity and no ocular adverse effects were
encountered. The long-term use of vigabatrin for the treat-
ment of patients with epilepsy has been associated with
the development of visual field defects. Most published
studies
2,6,12
have used Goldmann kinetic perimetry to
screen and observe vigabatrin-treated patients.
Automated achromatic perimetry with various test-
ing strategies has been used to study small groups of pa-
tients treated with vigabatrin. In 1 study
13
of 32 patients
who had taken vigabatrin for at least 3 years, visual field
testing with HFA revealed bilateral abnormalities in 19
(59%) of the patients compared with 0 of the 120 drug-
free control subjects. The program used for testing in this
study was the Humphrey 120-point, suprathreshold,
3-zone static perimetry test.
13
In another previous re-
port,
14
33 sequential patients who began receiving viga-
batrin were referred for ophthalmologic evaluation, in-
cluding visual field testing with HFA 30-2 and Esterman
or Octopus 32. Twenty-nine patients were able to com-
plete testing. Of these patients, only 32% showed no vi-
sual field constriction (68% had slight to severe visual
field constriction).
14
In another report
15
of visual field test-
ing with HFA 30-2 in 15 children receiving long-term
vigabatrin therapy, visual field defects were observed in
3 (20%). These were described as bilateral, symmetric,
nasal defects.
In this study, we used achromatic automated thresh-
old perimetry to 60°. We selected HFA 60-4 because it
provides full-threshold testing. Although this program
is associated with high variability, we believed it would
provide data for more robust analyses than a screening
program (such as the 120-point screening test). Our
rationale is that for future clinical trials, a standardized
method would need to be developed and significant
new visual field defects would be detectable with this
Table 2. Group Objective Visual Field Quadrant Sensitivity Analysis Before and After Treatment
Quadrant
Sensitivity
Before Treatment,
Mean (SD), dB RMSE/Mean, %
Sensitivity
After Treatment,
Mean (SD), dB Mean Change, % P Value
Right Eye
I/N 310.2 (66.0) 24 334.0 (45.7) 11.6 .09
I/T 418.8 (44.5) 15 435.9 (25.8) 5.3 .11
S/N 278.6 (47.4) 15 293.4 (44.5) 7.4 .13
S/T 335.9 (45.1) 11 341.9 (28.7) 3.3 .36
Left Eye
I/N 302.8 (46.7) 16 322.8 (61.9) 6.8 .06
I/T 426.3 (28.3) 6 428.5 (30.4) 0.7 .67
S/N 269.9 (59.6) 20 266.9 (45.4) −3.5 .62
S/T 335.8 (36.8) 14 343.7 (31.2) 3.1 .26
Abbreviations: I/N, inferonasal; I/T, inferotemporal; RMSE, root mean square error; S/N, superonasal; S/T, superotemporal.
Table 3. Group Objective Visual Field Quadrant Sensitivity Analysis With Censored Superior Points Before and After Treatment
Quadrant
Sensitivity
Before Treatment,
Mean (SD), dB RMSE/Mean, %
Sensitivity
After Treatment,
Mean (SD), dB Mean Change, % P Value
Right Eye
S/N 231.6 (33.7) 15 248.1 (27.3) 9 .05
S/T 285.8 (30.2) 9 295.2 (13.4) 5 .17
Left Eye
S/N 229.0 (45.6) 18 232.2 (24.6) 5 .35
S/T 284.8 (25.4) 10 293.1 (16.8) 3 .08
Abbreviations: See Table 2.
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protocol. While we cannot be certain that there were no
extremely peripheral changes beyond the limits of the
HFA 60-4 test, we would have expected to be able to
detect vigabatrin-associated visual field loss with
this strategy. In marked contrast with the reports
previously described, none of our subjects developed
confirmable visual field loss. In addition, we used the
HFA 24-2 test in 1 eye of each subject to probe for
subtle central defects. Our rationale was that the avail-
ability of normative data for central testing might allow
for the detection of central depressions. There were
none.
The subjective evaluation showed that most of the
observed field defects in our study were peripheral in
the superior and nasal quadrants, and were mostly due
to the eyelid, eyebrow, or nose obscuring parts of the
peripheral fields. Facial anatomy can obscure the test
object in peripheral visual field programs. A drooping
upper eyelid or an incorrect head position during the
visual field test may produce such artifacts. Nasal
peripheral visual field defects were also predominant in
previously reported studies.
16
With proper patient
instruction and head positioning, these defects were not
reproduced in any of the 11 patients exhibiting them.
In no subjects were concentric peripheral defects
observed. The pattern of peripheral superior and nasal
defects observed in the 11 subjects was not consistent
with the concentric pattern of field loss attributed to
vigabatrin in other studies. More importantly, the
defects were not reproduced, and the fields returned to
baseline status on retesting. We believe that there was
testing artifact from the eyebrow and nose.
We performed group and individual objective analyses
of the peripheral fields. In the group analysis, the total sen-
sitivity in all quadrants for both eyes did not diminish dur-
ing the study. Actually, all of the observed change was in
the positive direction, with improvement in total quad-
rant scores. It may be that improved test performance and
patient cooperation have contributed to the improved pe-
ripheral field scores. It is also likely that once patients were
abstinent from drug abuse, they performed better on visual
field testing. To reduce any possible confounding effects
of our subjects becoming better test takers by training and
being free from drug abuse, we did not use training fields
in the analysis, and all tests analyzed had good reliability
variables. Whether the subjects’ abstinence from cocaine
and/or methamphetamine affected their measured visual
field sensitivity remains unknown.
One concern with the study population was drop-
outs. Most of the subjects who began receiving vigaba-
trin had visual field data available for safety analysis.
Many subjects (n=42) were screened for the study but
never started receiving the study drug. This is not sur-
prising given the population of active substance abus-
ers. Of those subjects motivated enough to complete
the dose escalation phase, retention was excellent (18
[90%] of 20 subjects). The cumulative maximum viga-
batrin dose received among completers in the study
was 137 g, less than 10% of the lifetime exposure at
which there seems to be an increase in the incidence
of visual field abnormalities. In 1 study,
17
subjects who
had taken a total dose of 1500 g or more of vigabatrin
for epilepsy treatment were at risk of developing sig-
nificant visual field defects.
Vigabatrin-associated visual field loss was thought to
affect males more severely than females.
2
Of the 18 sub-
jects who completed this study, 17 were males. One might
expect our population to be at higher risk for vigabatrin-
associated field loss, but we do not believe we studied a
uniquely low-risk population.
Digital imaging technologies and fundus photogra-
phy can identify retinal nerve fiber layer attenuation in
subjects receiving long-term vigabatrin treatment of epi-
lepsy.
18,19
The sensitivity of these imaging modalities in
the detection of structural abnormalities after short-
term vigabatrin exposure is still unknown. Such tests may
provide additional means of monitoring for ocular safety
in future studies.
We have established an ocular safety protocol that
was clinically practical in the study of vigabatrin for
cocaine and/or methamphetamine abuse. Study subjects
were able to perform reliable automated threshold
perimetry. The absence of any detectable ocular adverse
effects or changes in visual field with this relatively low-
dose and short-term regimen of vigabatrin is promising
with regard to its safety in the short-term treatment of
drug abuse.
We recognize the limitations of this pilot trial
because it was a nonrandomized open-label study with-
out a control group. Our findings suggest that there can
be further study of vigabatrin for the treatment of drug
abuse without undue concern about ocular safety and
with proper rigorous monitoring of the visual field.
Furthermore, in this challenging population, subjects
were able to perform visual field testing reliably enough
to allow meaningful ocular safety monitoring. Consid-
ering the significant morbidity associated with cocaine
or methamphetamine abuse, vigabatrin seems promis-
ing and worthy of further study.
Submitted for Publication: November 17, 2005; final re-
vision received March 28, 2006; accepted April 3, 2006.
Correspondence: Robert D. Fechtner, MD, Institute of
Ophthalmology and Visual Science, University of Medi-
cine and Dentistry of New Jersey–New Jersey Medical
School, 90 Bergen St, Suite 6100, Newark, NJ 07103
(Fechtner@umdnj.edu).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by
Research to Prevent Blindness and by a grant (for the clini-
cal trial on which the analysis is performed) from Cata-
lyst Pharmaceutical Research LLC.
Acknowledgment: We thank Jeff Gornbein, DrPH, of the
Statistical/Biomathematical Consulting Clinic, Depart-
ment of Biomathematics, David Geffen School of Medi-
cine at UCLA.
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    • " reported in an eight week study that vigabatrin has been effective in the therapy of cocaine and/or methamphetamine dependence with no ocular adverse effects were observed. [39] In a recent clinical trials investigating the effect of anticonvulsant drugs for cocaine dependence, no evidence has shown the clinical use of vigabatrin in the treatment of patients with cocaine dependence. [40] They also suggested that vigabatrin cannot be considered first-, second-or third-line treatment for cocaine dependence. In co"
    [Show abstract] [Hide abstract] ABSTRACT: In the central nervous system, several lines of evidence suggest that the well-characterized inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved directly and/or indirectly in the pathogenesis of many neuropsychiatric disorders such as Alzheimer's disease, epilepsy, depression, schizophrenia, anxiety and some other disorders. Accordingly, deficiency in the GABA-ergic system activity in the brain should produce convulsion. Consequently, manipulation of the GABA-ergic activity seems to represent a possible treatment for epilepsy which has extensively been explored. Vigabatrin, an irreversible inhibitor of the catabolic enzyme of GABA (GABA-transaminase), is accepted as adjunct therapy of refractory partial seizures and infantile spasms. Although vigabatrin was demonstrated to be effective, its use is limited by the risk of retinopathy and associated peripheral visual field defects. Thus, this review highlights and assesses the accessible literature of the fundamental and clinical aspects of the GABA-transaminase inhibitor vigabatrin.
    Full-text · Article · Jul 2015
    • "Although the study delivered promising findings a weakness was the lack of a control group. Another study that examined the same 18 participants for their safety outcomes did not find changes in the visual field or abnormalities in visual acuity or ocular adverse effects (Fechtner et al., 2006). Topiramate. "
    [Show abstract] [Hide abstract] ABSTRACT: Methamphetamine (MA) is a public health problem both in Australia and internationally and very little is known about the most cost-effective treatment options. This study is a review of recent studies and an assessment of current treatment options for MA dependence. Treatment options for MA dependence can be divided into outpatient and inpatient modality settings according to the level of drug use. Moderate improvements through higher rates of retention in treatment (especially residential rehabilitation) have been found in individuals who completed either cognitive-behavioural therapy or counselling as a form of outpatient treatment and in those users who completed a residential rehabilitation treatment programme at an inpatient treatment modality. There remains a need for further research to investigate the efficacy of existing treatment options in individuals with MA use problems and to address the economic impact of those interventions in terms of cost-effectiveness/cost utility.
    Full-text · Article · Aug 2012
    • "Controlled clinical trials are underway to further evaluate the effects of vigabatrin (Brodie et al., 2005). It should be noted that while visual safety for short term use in cocaine addicts is established (Fechtner et al., 2006), peripheral field damage with long term use is possible (The Royal College of Ophthalmology, 2008). While facilitation of GABA activity shows evidence for reducing cocaine use, it is interesting to note that tiagabine, which blocks presynaptic release of GABA, also decreased cocaine use and increased abstinence rate in two controlled clinical trials (Gonzalez et al., 2007; Gonzalez et al., 2003). "
    [Show abstract] [Hide abstract] ABSTRACT: Addiction is a chronic relapsing brain disease and treatment of relapse to drug-seeking is considered the most challenging part of treating addictive disorders. Relapse can be modeled in laboratory animals using reinstatement paradigms, whereby behavioral responding for a drug is extinguished and then reinstated by different trigger factors, such as environmental cues or stress. In this review, we first describe currently used animal models of relapse, different relapse triggering factors, and the validity of this model to assess relapse in humans. We further summarize the growing body of pharmacological interventions that have shown some promise in treating relapse to psychostimulant addiction. Moreover, we present an overview on the drugs tested in cocaine or methamphetamine addicts and examine the overlap of existing preclinical and clinical data. Finally, based on recent advances in our understanding of the neurobiology of relapse and published preclinical data, we highlight the most promising areas for future anti-relapse medication development.
    Full-text · Article · Sep 2009
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