The Potential Role of Pharmacogenomics in Optimizing Drug Regimens for Older People with Major Depressive Disorder

2021 ◽  
Vol 36 (6) ◽  
pp. 276-282
Author(s):  
Jarvett M. Cox ◽  
Leisa L. Marshall

Major depressive disorder (MDD) is a mood disorder common in older individuals. While many clinical guidelines endorse the use of selective serotonin reuptake inhibitors (SSRIs) as first-line therapy in the treatment of MDD, the use of SSRIs in older populations can result in medication-related adverse events. The use of pharmacogenomic (PGx) testing as a personalized tool to determine optimal SSRI therapy could offer a means to decrease morbidity and improve overall quality of life in older people. This manuscript will review the epidemiology and criteria of MDD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), discuss the prevalence of MDD in older individuals, review the clinical treatment guidelines for the use of SSRIs in MDD, provide a brief overview of PGx testing, and present evidence for SSRI therapy modifications based on PGx testing.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shengwei Wu ◽  
Yufang Zhou ◽  
Zhengzheng Xuan ◽  
Linghui Xiong ◽  
Xinyu Ge ◽  
...  

AbstractThere is a large amount of evidence that selective serotonin reuptake inhibitors (SSRIs) are related to cardiovascular toxicity, which has aroused concern regarding their safety. However, few studies have evaluated the effects of SSRIs on cardiac injury biomarkers, such as creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether SSRIs elevated CK and CK-MB levels of prior medicated depressive patients (PMDP) compared to first-episode drug-naïve depressive patients (FDDPs). We performed an observational and retrospective study involving 128 patients with major depressive disorder. Patients who had never used any type of antidepressant were designated FDDP; patients who had used only one type of SSRI but were not treated after a recent relapse were designated PMDP. Serum CK and CK-MB levels were measured before and after using SSRIs for a period of time. The duration of current treatment in the FDDP and PMDP groups was 16.200 ± 16.726 weeks and 15.618 ± 16.902 weeks, respectively. After SSRI treatment, levels of serum CK in the PMDP group were significantly higher than in the FDDP group. Univariate ANCOVA results revealed that PMDP was 22.313 times more likely to elevate CK (OR 22.313, 95% CI 9.605–35.022) and 2.615 times more likely to elevate CK-MB (OR 2.615, 95% CI 1.287–3.943) than FDDP. Multivariate ANCOVA revealed an interaction between the group and sex of CK and CK-MB. Further pairwise analysis of the interaction results showed that in female patients, the mean difference (MD) of CK and CK-MB in PMDP was significantly greater than that in FDDP (MD = 33.410, P = 0.000, 95% CI 15.935–50.886; MD = 4.613, P = 0.000, 95% CI 2.846–6.381). Our findings suggest that patients, especially females, who had previously used SSRI antidepressants were more likely to have elevated CK and CK-MB, indicators of myocardial muscle injury. Use of SSRIs should not be assumed to be completely safe and without any cardiovascular risks.


Author(s):  
Susana Sousa ◽  
Constança Paúl ◽  
Laetitia Teixeira

Major depressive disorder (MDD) is one of the most common mental disorders in older people. There are several biological, psychological, and social factors associated with this disorder. This study aimed to describe the depressive state to identify the associated factors and potential predictors of MDD in a population of community-dwelling older people with probable MDD. The sample consisted of 378 participants with probable dementia, with 47.3% of them presenting MDD. The factors that were found to be associated with MDD were sex, living status, mobility, and nutritional status. Knowing the factors that can predict a condition such as MDD is extremely important, both for prevention and for the customization of interventions.


2019 ◽  
Vol 9 (6) ◽  
pp. 131 ◽  
Author(s):  
Michael Eggart ◽  
Andreas Lange ◽  
Martin Binser ◽  
Silvia Queri ◽  
Bruno Müller-Oerlinghausen

Interoception is the sense of the physiological condition of the entire body. Impaired interoception has been associated with aberrant activity of the insula in major depressive disorder (MDD) during heartbeat perception tasks. Despite clinical relevance, studies investigating interoceptive impairments in MDD have never been reviewed systematically according to the guidelines of the PRISMA protocol, and therefore we collated studies that assessed accuracy in detecting heartbeat sensations (interoceptive accuracy, IAc) in MDD (databases: PubMed/Medline, PsycINFO, and PsycARTICLES). Out of 389 records, six studies met the inclusion criteria. The main findings suggest that (i) moderately depressed samples exhibit the largest interoceptive deficits as compared with healthy adults. (ii) difficulties in decision making and low affect intensity are correlated with low IAc, and (iii) IAc seems to normalize in severely depressed subjects. These associations may be confounded by sex, anxiety or panic disorder, and intake of selective serotonin reuptake inhibitors. Our findings have implications for the development of interoceptive treatments that might relieve MDD-related symptoms or prevent relapse in recurrent depression by targeting the interoceptive nervous system.


CNS Spectrums ◽  
2009 ◽  
Vol 14 (6) ◽  
pp. 326-333 ◽  
Author(s):  
Susan G. Kornstein ◽  
Dayong Li ◽  
Yongcai Mao ◽  
Sara Larsson ◽  
Henning F. Andersen ◽  
...  

AbstractIntroduction: Recent data suggest that escitalopram may be more effective in severe depression than other selective serotonin reuptake inhibitors.Methods: Individual patient data from four randomized, double-blind comparative trials of escitalopram versus a serotonin/norepinephrine reuptake inhibitor (SNRI) (two trials with duloxetine and two with venlafaxine extended release) in outpatients (18–85 years of age) with moderate-to-severe major depressive disorder were pooled. The primary efficacy parameter in all four trials was mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score.Results: Significantly fewer escitalopram (82/524) than SNRI (114/527) patients prematurely withdrew from treatment due to all causes (15.6% vs. 21.6%, Fisher Exact: P=.014) and adverse events (5.3% vs. 12.0%, Fisher Exact: P <.0001). Mean reduction in MADRS score from baseline to Week 8 was significantly greater for the escitalopram group versus the SNRI group using the last observation carried forward (LOCF) approach [mean treatment difference at Week 8 of 1.7 points (P <.01)]. Similar results were observed in the severely depressed (baseline MADRS score ≥30) patient subset (mean treatment difference at Week 8 of 2.9 points [P <.001, LOCF]). Observed cases analyses yielded no significant differences in efficacy parameters.Conclusion: This pooled analysis indicates that escitalopram is at least as effective as the SNRIs (venlafaxine XR and duloxetine), even in severe depression, and escitalopram treatment was better tolerated.


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