Heavy drinking contributes to involuntary body movements such as akathisia. Quetiapine has been shown to alleviate symptoms of akathisia; however, its efficacy in the alcohol dependent population is not well established. Thus, we aimed to identify efficacy of Quetiapine in treating akathisia in very heavy drinking alcohol dependent patients. 108 male and female heavy alcohol consuming study participants received 13 weeks of Quetiapine XR. Drinking history (Timeline Followback, TLFB), depression (Montgomery-Asberg Depression Rating Scale, MADRS), and movement (Barnes Akathisia Scale, BARS) measures were collected at baseline (0 W), week 6 (6 W), and week 12 (12 W). The role of drinking, symptoms of depression, and efficacy of Quetiapine for treating akathisia were assessed. In patients with no symptoms of depression (low MADRS), Quetiapine treatment decreased symptoms of akathisia. Patients with clinically significant depression (high MADRS) reported a significant increase in akathisia measures at 6 W which eventually decreased at 12 W to below baseline levels. The increase in akathisia at 6 W corresponded with a significant increase in the patients’ total drinks and heavy drinking pattern. Treatment with Quetiapine progressively lowered the occurrence of akathisia in alcohol dependent patients who do not show symptoms of depression. Quetiapine treatment lowered akathisia over time in heavy drinkers who had clinically significant symptoms of depression.
Alcohol dependence is a major public health concern worldwide. Excessive consumption of alcohol over a prolonged period can have adverse neurocognitive effects [
The FDA has approved Quetiapine (Seroquel®) for the treatment of schizophrenia, bipolar disorder, and depression. Most clinical trials conducted so far have shown efficacy of Quetiapine to alleviate symptoms of depression, anxiety, and insomnia [
Patients with concomitant alcohol dependence and depression share a common underlying molecular neuropathology and therefore have similar clinical phenotypic presentation [
This study is one of the investigational arms of a larger protocol (ClinicalTrials.gov:
Baseline demographics, drinking history markers, and acute withdrawal assessment in alcohol dependent patients by MADRS group and gender.
Treatment and measures | Low MADRS (clinically nonsignificant) | High MADRS (clinically significant) | Significance between the MADRS grs. ( | ||||
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Males (63) | Females (14) | Overall (77) | Males (27) | Females (4) | Overall (31) | ||
Age (yrs.) | 44.4 ± 10.0 | 49.9 ± 8.5 | 45.43 ± 9.919 | 46.0 ± 8.1 | 41.8 ± 4.3 | 45.42 ± 7.749 | NS |
Weight (lb.) | 194.9 ± 40.8 | 153.2 ± 27.6 | 187.34 ± 41.8 | 195.1 ± 35.0 | 174.3 ± 35.4 | 192.4 ± 35.2 | NS |
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TD90 | 1268.9 ± 503.5 | 1030.0 ± 507.8 | 1225.5 ± 509.4 | 1370.0 ± 587.3 | 1064.8 ± 309.1 | 1328.8 ± 564.9 | NS |
AvgDPD90 | 14.1 ± 5.6 | 11.4 ± 5.6 | 13.6 ± 5.6 | 15.2 ± 6.5 | 11.8 ± 3.4 | 14.8 ± 6.2 | NS |
HDD90 | 63.1 ± 22.7 | 72.1 ± 13.1 | 64.8 ± 21.5 | 67.7 ± 24.7 | 76.0 ± 16.2 | 68.7 ± 23.7 | NS |
NDD90 | 80.5 ± 15.1 | 81.3 ± 13.7 | 80.62 ± 14.7 | 79.1 ± 13.6 | 83.8 ± 6.5 | 79.7 ± 12.9 | NS |
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CIWA BL | 1.7 ± 2.0 | 1.1 ± 2.4 | 1.6 ± 2.1 | 3.6 ± 2.6 | 3.5 ± 3.5 | 3.6 ± 2.7 | ≤0.001 |
CIWA 6 W | 0.9 ± 1.3 | 0.6 ± 1.2 | 0.9 ± 1.2 | 1.1 ± 1.4 | 0.7 ± 1.2 | 1.0 ± 1.3 | NS |
CIWA 12 W | 1.1 ± 1.4 | 0.1 ± 0.3 | 0.9 ± 1.4 | 1.1 ± 1.6 | 1.7 ± 0.6 | 1.2 ± 1.5 | NS |
TD90: total drinks in 90 days; AvgDPD90: average drinks per drinking day in last 90 days; HDD90: heavy drinking days in last 90 days; NDD90: number of drinking days in last 90 days.
The inclusion criteria used in this study were diagnosis of alcohol dependence (using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and age between 18 and 64 years. Men consumed 10 or more drinks per day while women consumed 8 or more drinks per day for at least 40% of the last 60 days of the 90-day drinking assessment (Timeline Followback, TLFB), and all subjects had 0.00 breath alcohol level at the time of consent. Major exclusions included other psychoactive drug dependence within the last year, positive urine screen for drugs, participation in other pharmacological/behavioral studies within the last three months, lifetime diagnosis of major depression or eating disorder, use of antidepressants (last 30 days) and/or antipsychotics (last 14 days) before randomization, and a score ≥10 on the Clinical Institute Withdrawal Assessment of Alcohol.
Study participants received Quetiapine XR (Seroquel XR® AstraZeneca, Wilmington, DE) for three months in 50 and 200 mg tablets [
Individual demographics were collected including age (years), sex (male or female), weight (lbs.), and drinking (TLFB) history. Age, weight, and recent drinking were included as covariates as needed. We used the following recent TLFB measures [
Patients were categorized by their MADRS scores at baseline (high MADRS or clinically significant if > seven; and low MADRS or clinically nonsignificant level if ≤ seven) [
There were three times as many men as women in this study, but since this occurred in all groups evenly, it did not restrain the analysis; however between sex analysis could not be performed. There were a few dropouts during the course of the study and 4-5% of the total data points could not be included from this study due to missing values. Statistical analysis data were not conclusive at week 12 due to lowered prevalence of akathisia since by then their symptoms most likely got better with treatment.
Out of 108 enrolled patients, 31 patients showed clinically significant level of depression using the MADRS scale. Demographic measures were comparatively similar in all subgroups differentiated by MADRS group (Table
We performed repeated analysis of variance to measure severity of akathisia using BARS assessment at week 6 and week 12 comparing from baseline values to identify if there is any significant contrast existing between the timelines due to MADRS reporting. We found that there was a significant contrast of time,
Thereafter, we conducted Chi-square tests to evaluate significance of occurrence of akathisia during Quetiapine treatment course by depression level (Table
Comparison of reported akathisia in alcohol dependent patients with clinically significant (high) and clinically nonsignificant (low) MADRS at baseline (0 weeks) and 6-week and 12-week assessment timelines.
Week/s | % akathisia incidence | Likelihood ratio | | Probability | |
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Low MADRS | High MADRS | ||||
0 | 15.6 | 19.7 | 0.221 | 0.638 | Low |
6 | 11.9 | 44.4 | 5.108 | 0.024 | Moderate |
12 | 3.7 | 9.1 | 0.583 | 0.445 | Low |
Level of drinking in alcohol dependent patients by MADRS group and reporting of akathisia. (a) Baseline total drinks (TD30) by MADRS and akathisia. (b) Total drinks (TD weeks 4–6) at week 6 by MADRS and akathisia. (c) Total drinks (TD weeks 10–12) at week 12 by MADRS and akathisia. Data presented as M ± SE (mean with standard error). Significance was set at
0 weeks
6 weeks
12 weeks
In the low MADRS group, the occurrence of akathisia continuously dropped during the entire treatment course with a 5-fold lowering at 12 W from the baseline occurrence (0 W), which also supports the role of Quetiapine in reducing akathisia in heavy drinking alcoholic patients without any ongoing clinically significant depression, who were actively drinking. Thus, the primary aim of this study was to determine if Quetiapine XR reduces akathisia in alcohol dependent patients. We found that it did in both depression groups. Akathisia is generally associated with the sense of inner restlessness, mental uneasiness, unrest, or dysphonia, which can be intense [
Based on our findings, we also report that there was an increase in akathisia in high MADRS group at 6 weeks of treatment, and it was important to identify the cause for such an increase. Akathisia has also been reported to be either primary or secondary to drug use [
Total drinks (marker of heavy drinking) recorded at all time points were higher in patients who exhibited akathisia in the high MADRS group. We did not find any significant differences in drinking either at baseline (0 W) or at the end of the study (12 W) between patients that exhibited akathisia and those that did not (Figures
Heavy drinking days (another marker of heavy drinking from TLFB questionnaire, HDD30) at baseline were higher in patients with akathisia in the high MADRS group. However, they were higher at both 6-week and 12-week assessments (Figures
Frequency of heavy drinking days (HDD) in alcohol dependent patients by MADRS and reporting of akathisia. (a) Baseline (0 weeks) frequency of heavy drinking days (HDD30) by MADRS and akathisia. (b) Heavy drinking days (TD weeks 4–6) at week 6 by MADRS and akathisia. (c) Heavy drinking days (TD weeks 10–12) at week 12 by MADRS and akathisia. Data presented as M ± SE (mean with standard error). Significance was set at
0 weeks
6 weeks
12 weeks
Both the amount and pattern of heavy drinking were influential in increasing the incidence of akathisia in the high MADRS group at six weeks. The amount and pattern of heavy drinking were lower in this group both at baseline and at 12 weeks of treatment. On the other hand, in the low MADRS group, we did not find any significant increase in patterns of heavy drinking during treatment, and the occurrence of akathisia progressively decreased over time. Thus, we did not observe any influence of drinking alone or its interaction with Quetiapine in patients who did not have clinically significant symptoms of depression. No other markers of drinking showed any significant differences between the two groups. We did not find any interaction between MADRS groups and the presence of akathisia.
Quetiapine XR seemed to alleviate akathisia symptoms in very heavy drinking alcohol dependent (AD) patients who did not have clinically significant symptoms of depression. In alcohol dependent patients with clinically significant symptoms of depression, the effects of Quetiapine XR in reducing akathisia do not seem to begin until after the first six weeks of treatment. Increases in the amount and pattern of heavy drinking potentially played a significant role in exacerbation of akathisia symptoms in heavy drinking AD patients. However, with continued treatment of Quetiapine XR, AD patients showed a significant lowering of the incidence of akathisia. Results from the present study extend our understanding of the interplay between heavy drinking, presence of clinically significant symptoms of depression, and the efficacy of Quetiapine XR in alleviating symptoms of akathisia in very heavy drinking alcohol dependent patients. Akathisia has been reported to either worsen or emerge as a new symptom during alcohol withdrawal in chronic alcoholics [
Quetiapine fumarate XR
Alcohol dependents
Montgomery-Asberg Depression Rating Scale
Barnes Akathisia Rating Scale
Timeline Followback
Medical management
0 W
6 W
12 W.
All authors declare no conflict of interests.
This study was supported by the following Grant: NIAAA (NIH): CSP-1027 (Vatsalya Vatsalya). Ms. Marion McClain provided editorial support.