The objective inthis randomized, double-blinded, placebo-controlled study was to examine thebenefit of using citalopram to treat non-depressed patients with mild tomoderate alcohol dependence.
The trial focused on the difference in outcomescomparing men and women. This study included 61 participants of whom 34 weremen and 27 were women. Subjects were included if they consumed at least 28drinks per week for at least 3 months and demonstrated mental and socialstability as well as if they met the criteria for mild to moderate alcoholdependence assessed by the Alcohol Dependence Scale (ADS), Michigan AlcoholScreening Test (MAST) and the Diagnostic Statistical Manual of MentalDisorders, 3rd edition, revised (DSM-III-R). Subjects were excludedif they had a prior additional drug or substance addiction, were clinicallydepressed, or diagnosed with an anxiety or psychiatric disorder. Once recruitedfor the study, subjects underwent a single-blind two-week baseline treatmentwith a placebo to determine response to the placebo alone. Those who met theinclusion criteria after the two-week placebo trial were then divided into twogroups: the treatment group and the placebo group. In the treatment group (n=16 men, 15 women), the subjects were provided with 40 milligrams of citalopramby mouth once daily and a brief psychosocial intervention (BPI) for 12 weeks.
Subjects in the placebo group (N=18 men, 12 women) received the placebo bymouth once daily and BPI for 12 weeks. The primary outcome of the study was toexamine the fluctuation of alcohol dependence between males and femalesdetermined by the ADS and MAST. Secondary outcomes included other psychiatricalterations as determined by the Montgomery-Åsberg Depression Rating Scale(MADRS) and the State-Trait Anxiety Inventory.
Subjects were told to takemedication at 8 pm and provide urine for analysis two to four hours following,which would either confirm or deny alcohol consumption and adherence totreatment. Subjects were required to return for scheduled visits at weeks 2, 4,6, 8 and 12. At these visits, subjects had an analysis of blood and urine, BPIand were asked to complete questionnaires to determine dependence. The p-valuewas set at 0.05, although the study failed to provide exact p-values forcomparisons. The study examined the mean drinks per day comparing males andfemales and showed citalopram had an additional 16.
57% decrease from baselinein men (p<0.05). The author concludedthere was a statistically significant difference in the reduction of meandrinks per day between men and females, with men benefiting more from thetreatment. Beforethis study was initiated, most of the previous studies on selective serotoninreuptake inhibitors (SSRI) in alcohol dependence were done primarily on men.This trial studied the effects on both men and women as well as the differencesbetween them. The duration of the study was brief at only 12 weeks, making ithard to effectively draw conclusions about relapse and outcomes after the studywithout further follow-up information. The study stated it published most ofthe results elsewhere, including liver function tests, perception of treatmentand post-treatment MAST and ADS scores. These results would be helpful inassessing a more complete picture of effectiveness.
One key baseline differencewas the MAST scores in the treatment group during initiation of the trial,which showed men at 10.4±0.8 and women at 6.4±0.
9 (p>0.05). Anything overfive indicated problems with drinking. This allowed for a higher margin ofimprovement for men than women and could have been avoided by an equaldistribution amongst groups. This study was supported by a grant from LundbeckPharmaceuticals. This could be a conflict of interest as the companymanufactures citalopram.
The company would benefit from another indication fortheir medication. Although there weremany secondary outcomes mentioned, the study only demonstrated a statisticaldifference in the decline of mean drinks per day between men and women. Thisstudy provided a precedent for gender differences in the treatment of alcoholdependence with citalopram. Thisstudy was a randomized, double-blind, placebo-controlled trial that sought todemonstrate that the treatment of alcohol dependence with citalopram producesundesired results. The study recruited subjects (N=265) and randomized theminto two groups for a length of 12 weeks (N= 127 in placebo group and N=137 intreatment group). Participants were included if they were 18-65 years old andmet the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition(DSM-IV) diagnosis of alcohol dependence. Participants were excluded from thetrial if they had concurrent addiction to an additional substance and apsychiatric disorder, if they were pregnant or breastfeeding, intolerant orallergic to SSRI, and if they were required to be admitted to inpatient foralcohol detoxification or psychiatric issue. The treatment group received 20milligrams of citalopram by mouth once daily for the first week and 40milligrams of citalopram once daily for the rest of the treatment.
Both theplacebo group and the treatment group underwent weekly individual and grouppsychotherapy. Subjects were examined at week 12 to determine their alcoholaddiction, any symptoms of depression, and any other psychiatric disorders. Thep-value was set at 0.
05. The primary outcome was the reduction of alcohol use,which showed that the placebo group had a 16.8% higher reduction in the numberof days of alcohol use from baseline compared to the treatment group (p=0.016).The placebo group also had a 20.62% reduction in the mean drinks per drinkingday when compared to treatment group (p=0.025).
Further comparison of secondaryoutcomes between the groups included the Hamilton Rating Scale for Depression(p=0.892), Beck Depression Inventory (p=0.841), and Beck Anxiety Inventory(p=0.
800); all of which did not demonstrate a statistical difference. The studyconcluded that citalopram should not be used in the treatment of alcoholdependence for the inferior outcomes associated. This study contradicts the findingsin the previous trial. The study contained more subjects and provided analysisof the groups focused on the change from baseline instead of variations betweenmen and women. This study stated thatmany subjects (n=124) had to withdraw from the trial because of worsening ofpsychiatric symptoms or adverse effects. However, follow up information from204 of the subjects was obtained. This furthers their conclusion aboutcitalopram and indicated that the trial could have been done for shorter timedue to harm or absence of effective treatment. The study used a noteworthyamount of men (n=185) compared to women (n=80).
The previous trial had shown aresponse difference to treatment between men and women. It would be helpful toseparate these results into two separate categories or recruit equal amounts toaccurately rule out clinical importance. Although detoxification was part ofthe exclusion criteria, it allowed subjects to receive a diazepam taperingregimen for 14 days prior to the trial if clinically indicated. This occurredin the treatment group significantly more than the placebo group (n=60 vs.n=33, p<0.
05). This could have affected the results of the studyas it may have introduced additional dependence or effected how either groupresponded to citalopram. Diazepam tapering regimen should have either beenomitted or distributed equally between groups. This study was conducted well in many aspects and it will help tofurther knowledge of the inappropriate treatment of alcohol dependence withSSRIs.