Effects of CYP2D6 genetic polymorphisms on the efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorder

Major depressive disorder (MDD) and alcohol use disorder (AUD) are leading causes of disability, and patients are frequently affected by both conditions. This comorbidity is known to confer worse outcomes and greater illness severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method that has demonstrated antidepressant effects. However, the study of rTMS for patients with MDD and commonly associated comorbidities, such as AUD, has been largely overlooked, despite significant overlap in clinical presentation and neurobiological mechanisms. This narrative review aims to highlight the interrelated aspects of the literature on rTMS for MDD and rTMS for AUD. First, we summarize the available evidence on the effectiveness of rTMS for each condition, both most studied through stimulation of the dorsolateral prefrontal cortex (DLPFC). Second, we describe common symptom constructs that can be modulated by rTMS, such as executive dysfunction, that are transdiagnostic across these disorders. Lastly, we describe promising approaches in the personalization and optimization of rTMS that may be applicable to both AUD and MDD. By bridging the gap between research efforts in MDD and AUD, rTMS is well positioned to be developed as a treatment for the many patients who have both conditions concurrently.

Download Full-text

Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0177 ◽

2019 ◽

Vol 97 (8) ◽

pp. 781-785 ◽

Cited By ~ 2

Author(s):

M.S. Zastrozhin ◽

V.Y. Skryabin ◽

V.V. Smirnov ◽

E.A. Grishina ◽

K.A. Ryzhikova ◽

...

Keyword(s):

Alcohol Use ◽

High Performance ◽

Alcohol Use Disorder ◽

Depressive Disorders ◽

Rating Scale ◽

Correlation Coefficients ◽

Inverse Correlation ◽

Efficacy And Safety ◽

Cyp2d6 Activity ◽

Scale Scores

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

Download Full-text

Pharmacological and Psychological Treatments for Comorbid Alcohol Use Disorder and Depressive Disorder: a Review

Current Addiction Reports ◽

10.1007/s40429-018-0213-z ◽

2018 ◽

Vol 5 (3) ◽

pp. 312-322 ◽

Cited By ~ 1

Author(s):

Gihyun Yoon ◽

Ismene L. Petrakis

Keyword(s):

Alcohol Use ◽

Depressive Disorder ◽

Alcohol Use Disorder ◽

Psychological Treatments

Download Full-text

Socio-economic inequalities in the association between alcohol use disorder and depressive disorder among Thai adults: a population-based study

BMC Psychiatry ◽

10.1186/s12888-020-02958-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Sawitri Assanangkornchai ◽

Jiraluck Nontarak ◽

Wichai Aekplakorn ◽

Suwat Chariyalertsak ◽

Pattapong Kessomboon ◽

...

Keyword(s):

Alcohol Use ◽

Depressive Disorder ◽

Rural Areas ◽

Urban Areas ◽

Alcohol Use Disorder ◽

Multinomial Logistic Regression ◽

Wealth Index ◽

Outcome Variable ◽

Health Examination ◽

Major Depressive

Abstract Background Previous evidence indicates significant associations between depressive disorders and alcohol use disorder (AUD) and their strong links with social conditions. This study aims to investigate the association between major depressive episode (MDE) and AUD across various socio-economic groups. Methods We analysed data from the 2014 Thai National Health Examination Survey containing a random sample of 13,177 adults aged > 20 years from the general population. The Alcohol Use Disorder Identification Test was used to classify respondents into non-problem drinking (score 0–7), hazardous drinking (score 8–15), and harmful-dependent drinking (score 16–40). MDE was identified using questions based on the DSM-IV. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated using multinomial logistic regression to determine the strength of associations between MDE as a predictor and AUD as an outcome variable across different socio-economic levels. Results The prevalence of MDE, hazardous, and harmful-dependent drinking was 2.5, 10.3, and 1.9%, respectively. The association between MDE and AUD was modified by wealth index, education level and area of residence. AORs for the association between MDE and harmful-dependent drinking were high among those in the highest (AOR = 8.68, 95% CI: 5.34, 14.11) and lowest (AOR = 7.14, 95% CI: 3.71, 13.73) levels of wealth index but not significant among those in the middle level (AOR = 1.78, 95% CI: 0.74, 4.25). Education had the strongest effect on the relationship between MDE and harmful-dependent drinking (AOR = 16.0, 95% CI: 10.30, 24.90 among those completing secondary school or higher and AOR = 1.44, 95% CI: 0.63, 3.33 among those completing primary school only). The association between MDE and harmful-dependent drinking was higher among people who lived in urban areas (AOR = 8.50, 95% CI: 5.50, 13.13) compared to those living in rural areas (AOR = 4.73, 95% CI: 3.31, 6.77). Conclusion Socio-economic factors modify the association between alcohol use disorder and major depressive disorder among Thai people.

Download Full-text

Clinical Outcomes of the First 2 Years of Implementation of the Integrated Care Pathway for Concurrent Major Depressive Disorder and Alcohol Use Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.251 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S79-S79 ◽

Cited By ~ 1

Author(s):

A.V. Samokhvalov ◽

S. Awan ◽

B. Le Foll ◽

C. Probst ◽

P. Voore ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Symptoms ◽

Alcohol Use ◽

Depressive Disorder ◽

Integrated Care ◽

Alcohol Use Disorder ◽

Care Pathway ◽

Retention Rates ◽

Major Depressive ◽

Integrated Care Pathway

BackgroundBoth major depressive disorder (MDD) and alcohol use disorder are highly prevalent, often comorbid and cause significant socioeconomic burden. At CAMH, we have developed and integrated care pathway (ICP) to treat these disorders and evaluated its effectiveness in comparison to treatment as usual (TAU)MethodsChart review; descriptive statistics, c2 and t-tests, linear mixed effects models, Kaplan–Meier and log-rank analyses.ResultsOverall, 81 patients were enrolled into ICP. Comparisons of treatment retention rates between ICP patients and matched historical controls (n = 81) showed significantly lower dropout rate in ICP cohort (18.5% vs. 69.1%, P < 0.001, Fig. 1). The ICP patients demonstrated significant reduction in depressive symptoms severity (QIDS: 14.6 vs. 10.0, P < 0.001; BDI 26.3 vs. 16.2, P < 0.001), reduction in the amount of alcohol consumed weekly from 44.6 standard drinks at baseline to 12.6 (P < 0.001) by the end of treatment, which was significantly better compared to controls (56.9 vs. 25.2, P < 0.001), P = 0.014 (Fig. 2).ConclusionsThe ICP is a feasible approach to treatment of concurrent AUD and MDD with significantly higher retention rates than TAU. Patients demonstrate improvements on several levels including depressive symptoms, and changes in alcohol drinking patterns.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text