A Study of Comparative Efficacy of Baclofen vs Acamprosate
Content
Research Article
A STUDY OF COMPARATIVE EFFICACY OF BACLOFEN VS
ACAMPROSATE IN REDUCING ALCOHOL CRAVING
AND ABUSE
*Suvendu N Mishra,
**S. P. Swain, **R K Shukla, **P.Sarkar
*IMS & SUM Hospital, Bhubaneswar.
**Mental Health Institute, SCB Medical college,Cuttack
treated with baclofen compared with
acamprosate.
INTRODUCTION
Approximately 4%of global burden of
disease can be attributed to alcohol
consumption. (1)-alcohol dependence (also
termed alcoholism) constitutes the most
serious alcohol use disorder, affecting nearly
14% of the general population.(2)-in addition
to alcohol dependence, unhealthy alcohol
consumption includes other alcohol use
disorder such as alcohol abuse and the less
severe but more frequent heavy drinking.(3)the high prevalence rate of unhealthy alcohol
consumption highlights the importance of this
issue for public health and socioeconomic
impact. In recent years, the use of
pharmacotherapy together with psychosocial
interventions (including Alcoholics Anonymous
and various counseling approaches) has
enhanced the percentage of success in
maintaining alcoholic patients in remission and
assisting the development of a lifestyle
compatible with long-term alcohol abstinence.
However, to date, drugs with proven efficacy
are very few (Garbutt et al., 1999; Swift,
1999; Kranzler, 2000) and the discovery of
new medications capable of positively affecting
the components of alcohol dependence
syndrome, such as craving and loss of control
on drinking or protracted abstinence
symptoms, would represent an important step
forward in the treatment of patients with
alcohol problems (Garbutt et al., 1999).
BACK GROUND
The GABA â receptor agonist ,baclofen
has recently been shown to reduce alcohol
intake preferring rats and alcohol consumption
and craving in open studies in humans.
AIMS:- The present study was performed in
order to determine the comparative efficacy
of baclofen and acamprosate administration ,
inducing and maintaining abstinence and
reducing craving for alcohol in alcohol
dependent patients. METHODS:The study
was conducted in the Dept of psychiatry ,SCB
MCH, at O.P.D. setup for one year .The
patients subsequently randomized into two
groups to receive either open level Baclofen
or Acamprosate.The subjects in each group
was administered the OCDS(Obsessive
Compulsive Drinking Scale) to rate their
craving for alcohol.Subjects in the baclofen
group was administered baclofen at the dose
of 15mg/day for the first 3 day and 30 mg/
day subsequently for a total duration of 3
months.The subjects in the acamprosate group
was administered the drug at the dose of
666.66 mg thrice daily for 3 months .The
subjects in both the group was followed up
at monthly interval for 3 months.At each follow
up visit ,the subjects was rated on the OCDS.
RESULTS AND CONCLUSION
In the present study a significantly higher
number of patients who achieved and
maintained abstinence throughout the
experiment were found in the group of patients
48
The γ Gamma-amino butyric acid (GABAB)
receptor agonist, Baclofen is potent and stereo
selective, used clinically to control spasticity
(Davidoff, 1985). Recent preclinical
experiments have demonstrated the efficacy
of Baclofen in suppressing both alcohol
withdrawal signs in rats made physically
dependent on alcohol and voluntary alcohol
intake in alcohol-preferring rats (Colombo et
al., 2000, 2002). Moreover, preliminary
clinical open studies have confirmed the ability
of Baclofen to reduce alcohol craving and
intake (Addolorato et al., 2000b) and alcohol
withdrawal symptoms (Addolorato et al.,
2002) in alcohol-dependent patients.
Finally, it is now better recognized that
although abstinence remains the ultimate goal
in treating alcohol-dependent individuals, but
even reducing the frequency of heavy drinking
also has the major impact of decreasing
alcohol-related consequences and improving
quality of life.
The present study, first of its kind in Indian
patients ,was conducted in order to replicate
the findings reported by western studies with
regard to the antic raving action of
baclofen.The second arm of the study was
designed to compare the antic raving efficacy
of acamprosate with baclofen.
OBJECTIVES
The present study was performed in
order to determine the comparative efficacy
of baclofen and acamprosate administration
in
1. inducing and maintaining abstinence.
2. reducing craving for alcohol in alcohol
dependent patients.
MATERIALS & METHODS
PLACE OF STUDY
The study was under taken at mental
health institute,S.C.B medical college ,
Cuttack , during the period between October
,2008 to October 2009 .
SAMPLE OF STUDY
The study group consisted of patients
attending psychiatry department ,SCB MCH
,Cuttack as out patients and diagnosed as case
of Alcohol dependence.
SELECTION OF PATIENTS(STUDY
GROUP)
The diagnosis of alcohol dependence was
done using the (ICD-10)criteria.
INCLUSION CRITERIA
1. Age ranging from 18-70yrs.
2. Diagnosis of current alcohol dependence
according to the (ICD-10)criteria
3. Last alcohol intake reported to have
taken place in the 24hr preceding
observation.
4. Presence of a key relative.
EXCLUSION CRITERIA
1. presence of severe liver ,kidney ,heart
or lung diseases requiring urgent
medical attention.
2. currently under treatment for any mental
disorder with psychotic drugs .
3. any dependence to drug other than
nicotine
4. age greater than 70 years.
METHODOLOGY
The study group consisted of cases of
alcohol dependence attending the psychiatry
department . A semistructered interview
schedule based on ICD-10 criteria was used
for diagnosis of the patients ,which was
subsequently confirmed by a senior faculty
member of the department, after necessary
and relevant investigation and work up.
Prior to being taken up for study ,an
informed and written consent was obtained
from the patient .The relevant data including
the sociodemographic variables, were
recorded in the response sheet of patient taking
both the drugs.
After proper diagnosis ,those patients who
satisfy the various inclusion criteria was
provisionally taken up for study .patients given
49
3 consecutive months.The subjects in both
the group were followed up at monthly interval
for 3 months.At each follow up visit ,the
subjects were rated on the Obsessive
Compulsive Drinking Scale.
The results of the study were statistically
analyzed and comparison was made between
both the groups.
Observation
This section covers the observation made
about the different aspects of the study.
written informed consent was subsequently
randomized into two groups to receive either
open –label Baclofen or Acamprosate. The
subjects in each group were administered the
Obsessive Compulsive Drinking Scale to rate
their craving for alcohol.Subjects in the
Baclofen group were administered Baclofen
at the dose of 15mg/day for the first 3 day
and 30 mg/day subsequently for a total duration
of 3 consecutive months.The subjects in the
Acamprosate group were administered the
drug at the dose of 666.66 mg thrice daily for
Table-1
Sample initially considered
Patients excluded
Patients taking Baclofen
Patients taking Acamprosate
60
11
25
24
Table-2
Socio demographic profile of the study
Baclofen Gr (n=25)
Acamprosate Gr (n=24)
Age(years) mean±S.D
41.28±6.83
42.08±7.07
Married
16(64%)
16(68%)
>10yrs of education
13(52%)
15(63%)
Employed
15(60%)
17(72%)
Urban
14(56%)
15(64%)
Table-3
Mean obsessive drinking score
Weeks
Baclofen Gr
Acamprosate
Mean
SD
Mean
Wk0-wk4
9.76
1.87
3.83
Wk0-wk8
15.4
2.39
7.16
Wk0-wk12
17.32
2.67
10.33
Gr
SD
1.27
1.73
2.18
Students t –test(unpaired),p<0.05
The mean obsessive score for drinking alcohol in both the groups shows significant difference
starting from 4wk to 12wks.
50
Table -4
Mean compulsive drinking score
Weeks
Baclofen Gr
Acamprosate Gr
Mean
SD
Mean
SD
Wk0-wk4
11.32
2.41
3.29
1.26
Wk0-wk8
15.8
2.84
6.7
1.54
Wk0-wk12
17.84
3.02
10.37
2.08
Students t –test(unpaired),p<0.05
The mean compulsive score for drinking alcohol in both the groups shows significant
difference from 4wk to 12wk.
Table-5
Total OCDS Score
Weeks
Baclofen Gr
Acamprosate Gr
Mean
SD
Mean
SD
Wk0-wk4
21.72
3.7
7.16
1.71
Wk0-wk8
31.4
3.9
13.58
2.28
Wk0-wk12
35.32
3.9
20.66
2.8
Students t –test(unpaired),p<0.05
The mean total obsessive compulsive score for drinking alcohol shows significant difference
in both the groups starting from 4wk to 12wks.
(Tab-3,4,)shows the craving score in the
Results
two
groups at different observation
During the course of the study 60
times.Unpaired t -test showed a significant
alcoholics subjects were initially recruited for
effect of both treatment and time on
the study,of which 11 were excluded leading
obsessive and compulsive drinking
to 49 patients finally taken up for the study,then
score,p<0.05,starting from week0-week12 the
they subsequently divided into two groups .
score in the baclofen group Constantly lower
The groups taking the drug baclofen were 25
than the acamprosate group.
and the groups taking the drug acamprosate
(Tab-5,)shows that the total OCDS
were 24. (Ref Tab -1)
score in the baclofen group was constantly
The age distribution (Ref Tab-2) of both
lower than acamprosate group.unpaired tthe groups taking baclofen and acamprosate
test,p<0.05.
showed that there is no significant difference
A significantly higher number of patients
regarding age on drinking of alcohol .similar
who achieved and maintained abstinence
findings were reported by Giovani
throughout the experiment were found in the
Addolorato et al 2006 in comparison
group of patients treated with baclofen
between diazepam and baclofen.
compared with acamprosate.
Regarding education ,employment
No serious systemic or single-organ
,marital status and domicile there is no
event leading to drug cessation was reported
difference between the two groups Fischers
and no patient discontinued the drug.
exact test,(p>0.05) (Addolorato et al.,)
Tolerability was fair in all patients; as previously
51
reported (Addolorato et al., 2000b), the most
common side-effects were sleepiness,
tiredness, vertigo ,pedal edema found in (3-4
patients) in the baclofen group and abdominal
pain (one patient ) in the acamprosate group,
which resolved within 1–2 weeks of drug
treatment and did not recur. No patient reported
euphoria or other pleasant effects caused by
the drug. No subject showed craving for
baclofen. At drug discontinuation, neither drug
withdrawal syndrome nor side-effect due to
drug suspension was observed.
DISCUSSION
Recent preclinical (Colombo et al.,
2000 , 2002) and preliminary clinical data
(Addolorato et al., 2000b, 2002) suggest
that the GABAB receptor agonist, baclofen, may
be effective in the treatment of patients with
alcohol problems. However, to date, no doubleblind, randomized placebo-controlled study has
been conducted. In spite of the limitation due
to the low number of patients evaluated, the
results of the present study indicate that
administration of relatively low doses of
baclofen to alcohol-dependent patients is more
effective than acamprosate in inducing and
maintaining abstinence from alcohol ( in terms
of number of patients reaching complete
abstinence ), reducing alcohol intake,
suppressing alcohol craving in both its
‘obsessive’ and ‘compulsive’ features.
In agreement with the previous
observation by (Addolorato et al., 2000b),
abstinence from alcohol or reduction in alcohol
intake was achieved within the first week of
baclofen treatment and was maintained
throughout the treatment period. The increased
efficacy of baclofen over acamprosate may
be related to its suppressant effect on craving;
indeed, the drug produced a rapid decrease in
the ‘compulsive’ and ‘obsessive’ components
of craving, as indicated by the immediate
reduction in mean score of both OCDS
subscales. It is noteworthy that an anti-craving
effect of baclofen has already been observed
with other substances of abuse, particularly
cocaine in cocaine users (Ling et al., 1998).
The anti-craving effect of baclofen may depend
on its ability to interfere with the neuronal
substrates mediating the reinforcing properties
of ethanol. GABAB receptors located in the
ventral tegmental area (VTA) have been
reported to control the activity of mesolimbic
dopamine neurons, a major neural pathway in
the regulation of the reinforcing properties of
addictive drugs, including alcohol (Di Chiara,
1995; Koob et al., 1998; Spanagel and
Weiss, 1999). Accordingly, pharmacological
stimulation of VTA GABAB receptors has been
found to inhibit the firing activity of these
neurons (Kalivas, 1993) as well as basal
(Yoshida et al., 1994) and alcohol-stimulated
(Carta et al., 2001) dopamine release from
their terminals in the nucleus accumbens.
Moreover, it is conceivable that the
suppressing effect of baclofen on alcohol
withdrawal symptomatology (Addolorato et
al., 2002) may have helped the patients to
achieve and maintain alcohol abstinence.
In contrast to the observation by
Krupitsky et al. (1993) that baclofen
ameliorates affective disorders in alcoholics,
in the present study baclofen was found to be
effective in reducing state anxiety, but not
current depression. It may be hypothesized that
the decrease in state anxiety found in the
present study and the decrease in depression
observed by Krupitsky et al. (1993) in
alcoholics after a 3-week treatment with
baclofen were secondary to the ability of
baclofen to achieve both a rapid detoxification
(Addolorato et al., 2002) and decrease in
craving, resulting in a rapid reduction of
physical and psychological symptoms.
LIMITATIONS:
Small sample size.
Absence of placebo group.
Absence of blinding.
Short follow up period.
52
6.
Duration of drinking and amount of
alcohol per day not recorded.
CONCLUSION
The study first of its kind in Indian
patients was able to replicate findings of
western studies,regarding the antic raving
action of Baclofen.
The results of the present study confirm
that baclofen, because of its anti-craving and
anti-reward action on one hand, and safety on
the other, has an important role in the treatment
of patients with alcohol abuse and
dependence.Further in comparison to
acamprosate it seems more effective in
reducing craving and maintaining abstinence
in the short term.
Studies with larger patient samples and
longer periods of observation are surely
warranted to confirm the results of the present
study.
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(2000b) Ability of baclofen in reducing alcohol
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L., Bernardi, M., Agabio, R., Colombo, G., Gessa,
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C., Pani, M., Reali, R., Addolorato, G. and Gessa,
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Carai M. A. M. and Gessa, G. L. (2002) The
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Address for Correspondence :
Dr. Suvendu Narayan Mishra
Asst. Professor, Dept of Psychiatry
IMS & SUM HOSPITAL,BBSR
E mail:[email protected]
53
A STUDY OF COMPARATIVE EFFICACY OF BACLOFEN VS
ACAMPROSATE IN REDUCING ALCOHOL CRAVING
AND ABUSE
*Suvendu N Mishra,
**S. P. Swain, **R K Shukla, **P.Sarkar
*IMS & SUM Hospital, Bhubaneswar.
**Mental Health Institute, SCB Medical college,Cuttack
treated with baclofen compared with
acamprosate.
INTRODUCTION
Approximately 4%of global burden of
disease can be attributed to alcohol
consumption. (1)-alcohol dependence (also
termed alcoholism) constitutes the most
serious alcohol use disorder, affecting nearly
14% of the general population.(2)-in addition
to alcohol dependence, unhealthy alcohol
consumption includes other alcohol use
disorder such as alcohol abuse and the less
severe but more frequent heavy drinking.(3)the high prevalence rate of unhealthy alcohol
consumption highlights the importance of this
issue for public health and socioeconomic
impact. In recent years, the use of
pharmacotherapy together with psychosocial
interventions (including Alcoholics Anonymous
and various counseling approaches) has
enhanced the percentage of success in
maintaining alcoholic patients in remission and
assisting the development of a lifestyle
compatible with long-term alcohol abstinence.
However, to date, drugs with proven efficacy
are very few (Garbutt et al., 1999; Swift,
1999; Kranzler, 2000) and the discovery of
new medications capable of positively affecting
the components of alcohol dependence
syndrome, such as craving and loss of control
on drinking or protracted abstinence
symptoms, would represent an important step
forward in the treatment of patients with
alcohol problems (Garbutt et al., 1999).
BACK GROUND
The GABA â receptor agonist ,baclofen
has recently been shown to reduce alcohol
intake preferring rats and alcohol consumption
and craving in open studies in humans.
AIMS:- The present study was performed in
order to determine the comparative efficacy
of baclofen and acamprosate administration ,
inducing and maintaining abstinence and
reducing craving for alcohol in alcohol
dependent patients. METHODS:The study
was conducted in the Dept of psychiatry ,SCB
MCH, at O.P.D. setup for one year .The
patients subsequently randomized into two
groups to receive either open level Baclofen
or Acamprosate.The subjects in each group
was administered the OCDS(Obsessive
Compulsive Drinking Scale) to rate their
craving for alcohol.Subjects in the baclofen
group was administered baclofen at the dose
of 15mg/day for the first 3 day and 30 mg/
day subsequently for a total duration of 3
months.The subjects in the acamprosate group
was administered the drug at the dose of
666.66 mg thrice daily for 3 months .The
subjects in both the group was followed up
at monthly interval for 3 months.At each follow
up visit ,the subjects was rated on the OCDS.
RESULTS AND CONCLUSION
In the present study a significantly higher
number of patients who achieved and
maintained abstinence throughout the
experiment were found in the group of patients
48
The γ Gamma-amino butyric acid (GABAB)
receptor agonist, Baclofen is potent and stereo
selective, used clinically to control spasticity
(Davidoff, 1985). Recent preclinical
experiments have demonstrated the efficacy
of Baclofen in suppressing both alcohol
withdrawal signs in rats made physically
dependent on alcohol and voluntary alcohol
intake in alcohol-preferring rats (Colombo et
al., 2000, 2002). Moreover, preliminary
clinical open studies have confirmed the ability
of Baclofen to reduce alcohol craving and
intake (Addolorato et al., 2000b) and alcohol
withdrawal symptoms (Addolorato et al.,
2002) in alcohol-dependent patients.
Finally, it is now better recognized that
although abstinence remains the ultimate goal
in treating alcohol-dependent individuals, but
even reducing the frequency of heavy drinking
also has the major impact of decreasing
alcohol-related consequences and improving
quality of life.
The present study, first of its kind in Indian
patients ,was conducted in order to replicate
the findings reported by western studies with
regard to the antic raving action of
baclofen.The second arm of the study was
designed to compare the antic raving efficacy
of acamprosate with baclofen.
OBJECTIVES
The present study was performed in
order to determine the comparative efficacy
of baclofen and acamprosate administration
in
1. inducing and maintaining abstinence.
2. reducing craving for alcohol in alcohol
dependent patients.
MATERIALS & METHODS
PLACE OF STUDY
The study was under taken at mental
health institute,S.C.B medical college ,
Cuttack , during the period between October
,2008 to October 2009 .
SAMPLE OF STUDY
The study group consisted of patients
attending psychiatry department ,SCB MCH
,Cuttack as out patients and diagnosed as case
of Alcohol dependence.
SELECTION OF PATIENTS(STUDY
GROUP)
The diagnosis of alcohol dependence was
done using the (ICD-10)criteria.
INCLUSION CRITERIA
1. Age ranging from 18-70yrs.
2. Diagnosis of current alcohol dependence
according to the (ICD-10)criteria
3. Last alcohol intake reported to have
taken place in the 24hr preceding
observation.
4. Presence of a key relative.
EXCLUSION CRITERIA
1. presence of severe liver ,kidney ,heart
or lung diseases requiring urgent
medical attention.
2. currently under treatment for any mental
disorder with psychotic drugs .
3. any dependence to drug other than
nicotine
4. age greater than 70 years.
METHODOLOGY
The study group consisted of cases of
alcohol dependence attending the psychiatry
department . A semistructered interview
schedule based on ICD-10 criteria was used
for diagnosis of the patients ,which was
subsequently confirmed by a senior faculty
member of the department, after necessary
and relevant investigation and work up.
Prior to being taken up for study ,an
informed and written consent was obtained
from the patient .The relevant data including
the sociodemographic variables, were
recorded in the response sheet of patient taking
both the drugs.
After proper diagnosis ,those patients who
satisfy the various inclusion criteria was
provisionally taken up for study .patients given
49
3 consecutive months.The subjects in both
the group were followed up at monthly interval
for 3 months.At each follow up visit ,the
subjects were rated on the Obsessive
Compulsive Drinking Scale.
The results of the study were statistically
analyzed and comparison was made between
both the groups.
Observation
This section covers the observation made
about the different aspects of the study.
written informed consent was subsequently
randomized into two groups to receive either
open –label Baclofen or Acamprosate. The
subjects in each group were administered the
Obsessive Compulsive Drinking Scale to rate
their craving for alcohol.Subjects in the
Baclofen group were administered Baclofen
at the dose of 15mg/day for the first 3 day
and 30 mg/day subsequently for a total duration
of 3 consecutive months.The subjects in the
Acamprosate group were administered the
drug at the dose of 666.66 mg thrice daily for
Table-1
Sample initially considered
Patients excluded
Patients taking Baclofen
Patients taking Acamprosate
60
11
25
24
Table-2
Socio demographic profile of the study
Baclofen Gr (n=25)
Acamprosate Gr (n=24)
Age(years) mean±S.D
41.28±6.83
42.08±7.07
Married
16(64%)
16(68%)
>10yrs of education
13(52%)
15(63%)
Employed
15(60%)
17(72%)
Urban
14(56%)
15(64%)
Table-3
Mean obsessive drinking score
Weeks
Baclofen Gr
Acamprosate
Mean
SD
Mean
Wk0-wk4
9.76
1.87
3.83
Wk0-wk8
15.4
2.39
7.16
Wk0-wk12
17.32
2.67
10.33
Gr
SD
1.27
1.73
2.18
Students t –test(unpaired),p<0.05
The mean obsessive score for drinking alcohol in both the groups shows significant difference
starting from 4wk to 12wks.
50
Table -4
Mean compulsive drinking score
Weeks
Baclofen Gr
Acamprosate Gr
Mean
SD
Mean
SD
Wk0-wk4
11.32
2.41
3.29
1.26
Wk0-wk8
15.8
2.84
6.7
1.54
Wk0-wk12
17.84
3.02
10.37
2.08
Students t –test(unpaired),p<0.05
The mean compulsive score for drinking alcohol in both the groups shows significant
difference from 4wk to 12wk.
Table-5
Total OCDS Score
Weeks
Baclofen Gr
Acamprosate Gr
Mean
SD
Mean
SD
Wk0-wk4
21.72
3.7
7.16
1.71
Wk0-wk8
31.4
3.9
13.58
2.28
Wk0-wk12
35.32
3.9
20.66
2.8
Students t –test(unpaired),p<0.05
The mean total obsessive compulsive score for drinking alcohol shows significant difference
in both the groups starting from 4wk to 12wks.
(Tab-3,4,)shows the craving score in the
Results
two
groups at different observation
During the course of the study 60
times.Unpaired t -test showed a significant
alcoholics subjects were initially recruited for
effect of both treatment and time on
the study,of which 11 were excluded leading
obsessive and compulsive drinking
to 49 patients finally taken up for the study,then
score,p<0.05,starting from week0-week12 the
they subsequently divided into two groups .
score in the baclofen group Constantly lower
The groups taking the drug baclofen were 25
than the acamprosate group.
and the groups taking the drug acamprosate
(Tab-5,)shows that the total OCDS
were 24. (Ref Tab -1)
score in the baclofen group was constantly
The age distribution (Ref Tab-2) of both
lower than acamprosate group.unpaired tthe groups taking baclofen and acamprosate
test,p<0.05.
showed that there is no significant difference
A significantly higher number of patients
regarding age on drinking of alcohol .similar
who achieved and maintained abstinence
findings were reported by Giovani
throughout the experiment were found in the
Addolorato et al 2006 in comparison
group of patients treated with baclofen
between diazepam and baclofen.
compared with acamprosate.
Regarding education ,employment
No serious systemic or single-organ
,marital status and domicile there is no
event leading to drug cessation was reported
difference between the two groups Fischers
and no patient discontinued the drug.
exact test,(p>0.05) (Addolorato et al.,)
Tolerability was fair in all patients; as previously
51
reported (Addolorato et al., 2000b), the most
common side-effects were sleepiness,
tiredness, vertigo ,pedal edema found in (3-4
patients) in the baclofen group and abdominal
pain (one patient ) in the acamprosate group,
which resolved within 1–2 weeks of drug
treatment and did not recur. No patient reported
euphoria or other pleasant effects caused by
the drug. No subject showed craving for
baclofen. At drug discontinuation, neither drug
withdrawal syndrome nor side-effect due to
drug suspension was observed.
DISCUSSION
Recent preclinical (Colombo et al.,
2000 , 2002) and preliminary clinical data
(Addolorato et al., 2000b, 2002) suggest
that the GABAB receptor agonist, baclofen, may
be effective in the treatment of patients with
alcohol problems. However, to date, no doubleblind, randomized placebo-controlled study has
been conducted. In spite of the limitation due
to the low number of patients evaluated, the
results of the present study indicate that
administration of relatively low doses of
baclofen to alcohol-dependent patients is more
effective than acamprosate in inducing and
maintaining abstinence from alcohol ( in terms
of number of patients reaching complete
abstinence ), reducing alcohol intake,
suppressing alcohol craving in both its
‘obsessive’ and ‘compulsive’ features.
In agreement with the previous
observation by (Addolorato et al., 2000b),
abstinence from alcohol or reduction in alcohol
intake was achieved within the first week of
baclofen treatment and was maintained
throughout the treatment period. The increased
efficacy of baclofen over acamprosate may
be related to its suppressant effect on craving;
indeed, the drug produced a rapid decrease in
the ‘compulsive’ and ‘obsessive’ components
of craving, as indicated by the immediate
reduction in mean score of both OCDS
subscales. It is noteworthy that an anti-craving
effect of baclofen has already been observed
with other substances of abuse, particularly
cocaine in cocaine users (Ling et al., 1998).
The anti-craving effect of baclofen may depend
on its ability to interfere with the neuronal
substrates mediating the reinforcing properties
of ethanol. GABAB receptors located in the
ventral tegmental area (VTA) have been
reported to control the activity of mesolimbic
dopamine neurons, a major neural pathway in
the regulation of the reinforcing properties of
addictive drugs, including alcohol (Di Chiara,
1995; Koob et al., 1998; Spanagel and
Weiss, 1999). Accordingly, pharmacological
stimulation of VTA GABAB receptors has been
found to inhibit the firing activity of these
neurons (Kalivas, 1993) as well as basal
(Yoshida et al., 1994) and alcohol-stimulated
(Carta et al., 2001) dopamine release from
their terminals in the nucleus accumbens.
Moreover, it is conceivable that the
suppressing effect of baclofen on alcohol
withdrawal symptomatology (Addolorato et
al., 2002) may have helped the patients to
achieve and maintain alcohol abstinence.
In contrast to the observation by
Krupitsky et al. (1993) that baclofen
ameliorates affective disorders in alcoholics,
in the present study baclofen was found to be
effective in reducing state anxiety, but not
current depression. It may be hypothesized that
the decrease in state anxiety found in the
present study and the decrease in depression
observed by Krupitsky et al. (1993) in
alcoholics after a 3-week treatment with
baclofen were secondary to the ability of
baclofen to achieve both a rapid detoxification
(Addolorato et al., 2002) and decrease in
craving, resulting in a rapid reduction of
physical and psychological symptoms.
LIMITATIONS:
Small sample size.
Absence of placebo group.
Absence of blinding.
Short follow up period.
52
6.
Duration of drinking and amount of
alcohol per day not recorded.
CONCLUSION
The study first of its kind in Indian
patients was able to replicate findings of
western studies,regarding the antic raving
action of Baclofen.
The results of the present study confirm
that baclofen, because of its anti-craving and
anti-reward action on one hand, and safety on
the other, has an important role in the treatment
of patients with alcohol abuse and
dependence.Further in comparison to
acamprosate it seems more effective in
reducing craving and maintaining abstinence
in the short term.
Studies with larger patient samples and
longer periods of observation are surely
warranted to confirm the results of the present
study.
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Address for Correspondence :
Dr. Suvendu Narayan Mishra
Asst. Professor, Dept of Psychiatry
IMS & SUM HOSPITAL,BBSR
E mail:[email protected]
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