The objective in this randomized, double-blinded, placebo-controlled study was to examine the benefit of treating non-depressed patients with mild to moderate alcohol dependence with citalopram. The trial focused on the difference in outcomes comparing men and women. This study included 61 participants of whom 34 were men and 27 were women.
Subjects were included if they consumed at least 28 drinks per week for at least 3 months, demonstrated mental and social stability as well as if they met the criteria for mild to moderate alcohol dependence assessed by the Alcohol Dependence Scale (ADS), Michigan Alcohol Screening Test (MAST) and the Diagnostic Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R). Subjects were excluded if they had a prior additional drug or substance addiction, were clinically depressed, or diagnosed with an anxiety or psychiatric disorder. Once recruited for the study, subjects underwent a single-blind two week baseline treatment with a placebo to determine response to the placebo alone. Those who met the inclusion criteria after the two week placebo trial were then divided into two groups: the treatment group and the placebo group. In the treatment group (n= 16 men, 15 women), the subjects were provided with 40 milligrams of citalopram by mouth once a day and a brief psychosocial intervention (BSI) for 12 weeks. Subjects in the placebo group (N=18 men, 12 women) received the placebo by mouth once a day and BSI for 12 weeks.
The primary outcome of the study was to examine the fluctuation of alcohol dependence between males and females determined by the ADS and MAST. Secondary outcomes included other psychiatric alterations as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS) and the State-Trait Anxiety Inventory. Subjects were told to take medication at 8 p.m. and provide urine for analysis two to four hours following, which confirmed or denied alcohol consumption and adherence to treatment. Subjects were required to return for scheduled visits at week two, week four, week eight and week twelve.
At these visits, subjects had an analysis of blood urine, BPI, and were asked to complete questionnaires to determine dependence. P-value was set at 0.05, although the study failed to provide exact p-values for comparisons. The study examined the mean drinks per day comparing males and females and showed citalopram had an additional 16.57% decrease in men (p<0.05). The author concluded that there was a statistically significant difference in the reduction of mean drinks per day between men and females, with men benefiting more from the treatment.1 Before this study was initiated, most of the previous studies on selective serotonin reuptake inhibitor (SSRI) in alcohol dependence were done primarily on men.
This trial studied the effects on both men and women as well as the differences between them. However, the study design needs to be amended. The duration of the study was brief at only 12 weeks, making it hard to effectively draw conclusions about relapse and outcomes after the study without further follow up information.
The study states it published most of the results elsewhere, including liver function tests, perception of treatment, and post-treatment MAST and ADS scores.2 These results would be helpful in assessing a more complete picture of treatment. One key baseline difference was 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).1 Anything over five indicated problems with drinking. This allowed for a higher margin of improvement for men than women. This study was supported by a grant from Lundbeck Pharmaceuticals.1 This could be a conflict of interest as the company manufactures citalopram. The company would benefit from another indication for their medication. Although there were many secondary outcomes mentioned, the study only demonstrated a statistical difference in the decline of mean drinks per day between men and women.
This study serves as a basis to many studies that have occured since. This study was a randomized, double-blind, placebo-controlled trial to demonstrate that the treatment of alcohol dependence with citalopram produces undesired results. The study recruited subjects (N=265) and randomized them into two groups (N= 127 in placebo group and N=137 in treatment group). Participants were included if they were 18-65 years old and met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of alcohol dependence.
Participants were excluded from the trial if they had concurrent addiction to an additional substance and a psychiatric disorder, if they were pregnant or breastfeeding, intolerant or allergic to SSRI, and if they were required to be admitted to inpatient for alcohol detoxification or psychiatric issue. The treatment group received 20 milligrams of citalopram by mouth once a day for the first week and 40 milligrams of citalopram once a day for the rest of the treatment. Both the placebo group and the treatment group underwent weekly individual and group psychotherapy. Subjects were examined at week 12 to determine their alcohol addiction, any symptoms of depression, and any other psychiatric disorders.
The p-value was set at 0.05, although specific p-values were never given. The primary outcome was the reduction of alcohol use, which showed that the placebo group had a 16.
8% higher reduction in the number of days of alcohol use from baseline compared to the treatment group (p=0.016). The placebo group also had 20.62% reduction in the mean drinks per drinking day when compared to treatment group (p=0.025). Further comparison of secondary outcomes 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 study concludes that citalopram should not be used in the treatment of alcohol dependence for the inferior outcomes associated.3 This study contradicts the findings in the previous trial. The study contained more subjects and provided analysis of the groups focused on the change from baseline instead of variations between men and women. This study states that many subjects (n=124) had to withdraw from the trial because of worsening of psychiatric symptoms or adverse effects.
However, follow up information from 204 of the subjects was obtained.3 This furthers their conclusion about citalopram and indicates that the trial could have been done for shorter time due to the harm or absence of effective treatment. The study used a noteworthy amount of men (n=185) compared to women (n=80).3 The previous trial had shown a response to treatment difference between men and women. It would be helpful to separate these results into two separate categories or recruit equal amounts to accurately rule out clinical importance. Although detoxification was part of the exclusion criteria, it allowed subjects to receive a diazepam tapering regimen for 14 days prior to the trial if clinically indicated.
This occured in the treatmentment group significantly more than the placebo group (n=60 vs. n=33, p<0.05).3 This could have affected the results of the study as it may have introduced additional dependence or effected how either group responded to citalopram. Diazepam tapering regimen should have either been omitted or distributed equally between groups.
This study was conducted well in many aspects and it will help to further knowledge of the inappropriate treatment of alcohol dependence with SSRIs.
