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. Author manuscript; available in PMC: 2025 Feb 1.
Published in final edited form as: Neurosci Biobehav Rev. 2023 Dec 22;157:105523. doi: 10.1016/j.neubiorev.2023.105523

Table 2.

Clinical studies on the morning vs. evening schedule of drug administration (≥ 50 subjects).

Drugs Subjects Type of Study Drug-Delivery Time Conclusions References
Simvastatin, 172 (33 male, 117 female) random Double blind, placebo-controlled study Evening vs Morning Evening is more effective than morning (Saito et al., 1991)
Simvastatin, 57 (27 men and 33 women), mean age 66 Randomized controlled trial Evening vs Morning Evening is more effective than morning (Wallace et al., 2003)
Valsartan, an ARBs 90 subjects (30 men and 60 women), Clinical trial Morning vs Evening No difference (Hermida et al., 2003)
Captopril, an ACEIs 121 (75 males, 46 females) Prospective, randomized, double-blind, placebo-controlled study Evening Restored the diurnal BP rhythm and decreased the elevated night/day BP ratio at bedtime administration (Qiu et al., 2005)
Phenytoin and carbamazepine 148 () 18-65 age Comparative study Evening Improved the response of diurnally active epileptic patients not responding to standard doses at bedtime administration (Yegnanarayan et al., 2006)
Telmisartan, ACEIs, and ARBs 215 (114 men and 101 women) (46.4+/−12.0 years) Randomized, double-blind, placebo-controlled trial Evening vs Morning Reduced BP during sleep at bedtime administration (Hermida et al., 2007)
Prednisone, a corticosteroid 288 (54·6 (11·2) 55·4 (41 men and 247 women), Randomized, double-blind Modified vs immediate Reduced morning stiffness of joints by modified release (Buttgereit et al., 2008)
Torsemide, a diuretic 113 (44 men and 69 women) (51.7+/−10.6 years) Randomized, double-blind Evening vs Morning More effective in lowering BP in patients with uncomplicated essential hypertension at bedtime (Hermida et al., 2008b)
Nifedipine, a CCBs 180 (52.5 +/−10.7 years) (86 men and 94 women) Randomized, double-blind Evening vs Morning Significantly reduced the bedtime edema at bedtime administration (Hermida et al., 2008c)
ACIE, ARB, CCB 250 (136 men and 114 women), 60.1±11.7 years of age Randomized, open-label, blinded endpoint (PROBE), parallel-group trial Evening vs Morning A larger reduction in BP at bedtime administration (Hermida et al., 2008a)
Vaccination (hepatitis A and influenza A) 164 (men and women) Clinical study Morning vs Afternoon Higher antibody response to both the hepatitis A and influenza A vaccines at morning vaccination (Phillips et al., 2008)
Olmesartan ACEIs and ARBs 123 (39 men and 84 women) (46.6+/−12.3 years) Randomized, double-blind Evening vs Morning Improved wake/asleep BP ratio at bedtime administration (Hermida et al., 2009)
Ramipril ACEIs and ARBs 115 (52 men and 63 women) (46.7+/−11.2 years) Randomized, double-blind Evening vs Morning Better nocturnal BP regulation at bedtime (Hermida and Ayala, 2009)
Amlodipine/valsartan, a CCBs and ARBs 203 (92 men/111 women), 56.7 +/− 12.5 years Single/Combined Evening vs Morning Improved the efficacy of lowering sleep BP and increasing sleep duration at bedtime administration (Hermida et al., 2010b)
ARBs, ACEIs, CCBs, β-blockers, and diuretics 2156 (1044 men/1112 women), MAPEC study Evening vs Morning The progressive decrease in asleep BP and increase in sleep-time were best achieved at bedtime therapy. (Hermida et al., 2010c)
Spirapril, an ACEIs 165 (65 men/100 women), 42.5 ± 13.9 [mean ± SD] yrs. of age) Open-label, parallel-group, blinded-endpoint Evening vs Morning Better sleep-time BP regulation at bedtime administration (Hermida et al., 2010a)
Valsartan/Hydrochlorothiazide, a diuretic, and ARBs 204 (95 men/109 women), (49.7 ± 11.1 years) An open-label, blinded endpoint Evening vs Morning Improved efficacy in lowering asleep BP and increased sleep time at bedtime administration (Hermida et al.,2011b)
Ezetimibe/simvastatin, statins 171 (87 in the morning and 84 in the evening administration group) > 18 years Randomized, crossover Morning vs Evening Morning administration was not inferior in lowering LDL-C (Yoon et al., 2011)
Antihypertensive drugs (ARBs e.g., valsartan; the ACEIs e.g., ramipril; and CCBs, e.g., amlodipine, etc.) 661 (396 men/265 women), (59.2 ± 13.5 years) PROBE trial Evening vs Morning Improved BP control and reduced risk of cardiovascular events at bedtime (Hermida et al., 2011a)
Aspirin, COX inhibitor 350 pregnant women (30.7 ± 5.3 years) Randomized, double-blind, placebo-controlled trial Evening vs Morning BP regulation and pregnancy outcome in high-risk pregnant women at bedtime administration (Ayala et al., 2013)
Prednisolone, a steroid 350 Primarily female (18–80 years) Randomized, double-blind, placebo-controlled trial Evening vs Morning Better reduction of morning stiffness of joints at bedtime administration (Buttgereit et al., 2013)
BP lowering drugs 2012 (976 men and 1,036 women), (52.7 ± 13.6 years) Prospective, PROBE trial Evening vs Morning Improved ambulatory BP control and reduced the risk of new-onset diabetes at bedtime administration (Hermida et al., 2016)
Influenza vaccination 276 adults (65+ age) Cluster-randomized trial Morning vs Afternoon Benefitted influenza antibody response at morning vaccination (Long et al., 2016)
ARB, ACEI, CCB, β-blocker, and/or diuretic 19084 (10614 men/8470 women), 60.5 ± 13.7 years of age Multi center, controlled, PROBE study Evening vs Morning Improved asleep ABP control and reduced CVD morbidity and mortality at bedtime administration (Hermida et al., 2019)
Aspirin, an NSAIDs 175 (59 women and 116 men), (59.8 years) Randomized controlled trial Evening vs Morning Reduced platelet aggregation at bedtime administration (Krasińska et al., 2019)
Ibuprofen, an NSAIDs 70 (men and women), (18-35 years) A randomized, double-blind, placebo-controlled trial Morning vs Morning Sufficient for pain management after surgical interventions at daytime administration (Tamimi et al., 2022)