TY  - JOUR
A1  - Stein, Kiera
A1  - Maruf, Abdullah Al
A1  - Müller, Daniel J.
A1  - Bishop, Jeffrey R.
A1  - Bousman, Chad A.
T1  - Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis
JF  - Journal of Personalized Medicine
N2  - Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion–deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.
KW  - 5-HTTLPR
KW  - genotype
KW  - pharmacogenetics
KW  - antidepressant
KW  - efficacy
KW  - tolerability
KW  - SLC6A4
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252294
SN  - 2075-4426
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Edelmann, Frank
A1  - Musial-Bright, Lindy
A1  - Gelbrich, Goetz
A1  - Trippel, Tobias
A1  - Radenovic, Sara
A1  - Wachter, Rolf
A1  - Inkrot, Simone
A1  - Loncar, Goran
A1  - Tahirovic, Elvis
A1  - Celic, Vera
A1  - Veskovic, Jovan
A1  - Zdravkovic, Marija
A1  - Lainscak, Mitja
A1  - Apostolović, Svetlana
A1  - Neskovic, Aleksandar N.
A1  - Pieske, Burkert
A1  - Düngen, Hans-Dirk
T1  - Tolerability and feasibility of beta-blocker titration in HFpEF versus HFrEF: Insights from the CIBIS-ELD trial
JF  - JACC: Heart Failure
N2  - OBJECTIVES: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. 
BACKGROUND: Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. 
METHODS: In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide). 
RESULTS: For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF. CONCLUSIONS: BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and Left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure HF] Patients: A Randomised, Double-Blind Multicentre Study CIBIS-ELD]; ISRCTN34827306).
KW  - beta-blockers
KW  - heart failure
KW  - HFpEF
KW  - HFrEF
KW  - tolerability
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191022
VL  - 4
IS  - 2
ER  -