Onset of Action of Selected Second-Generation Antipsychotics (Pines)-A Systematic Review and Meta-Analyses.

Recommendations for duration of treatment with antipsychotics before considering a switch vary from 2 to 8 weeks, although several studies suggest a rapid onset of action. The objective of this review was to estimate time to onset of action and time to maximum antipsychotic effect of asenapine, olanzapine, quetiapine, and zotepine (pines). We searched bibliographic databases for randomized, placebo-controlled trials in adults with schizophrenia estimating the antipsychotic effect of pines over time. Thirty-five studies including 6331 patients diagnosed with chronic schizophrenia were included. We estimated the standardized mean differences (SMD) of changes in symptom score from baseline to follow-up between intervention and placebo groups across studies using meta-analysis techniques. The summarized effect across all included pines administered as immediate-release formulations showed a statistically significant effect at week 1 (SMD, -0.20 [CI95% -0.28, -0.13]), which increased until week 3 (SMD, -0.42 [CI95% -0.50, -0.34]), after which the effect leveled off (week 6: SMD, -0.53 [CI95% -0.62, -0.44]). The sensitivity analyses of the individual pines confirm this finding, although data sparsity increases variability and limits conclusiveness of these analyses.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

BACKGROUND: Recent cohort studies show that salt intake below 6 g is associated with increased mortality. These findings have not changed public recommendations to lower salt intake below 6 g, which are based on assumed blood pressure (BP) effects and no side-effects. OBJECTIVES: To assess the effects of sodium reduction on BP, and on potential side-effects (hormones and lipids) SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to April 2018 and a top-up search in March 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. The top-up search articles are recorded under "awaiting assessment." SELECTION CRITERIA: Studies randomizing persons to low-sodium and high-sodium diets were included if they evaluated at least one of the outcome parameters (BP, renin, aldosterone, noradrenalin, adrenalin, cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride,. DATA COLLECTION AND ANALYSIS: Two review authors independently collected data, which were analysed with Review Manager 5.3. Certainty of evidence was assessed using GRADE. MAIN RESULTS: Since the first review in 2003 the number of included references has increased from 96 to 195 (174 were in white participants). As a previous study found different BP outcomes in black and white study populations, we stratified the BP outcomes by race. The effect of sodium reduction (from 203 to 65 mmol/day) on BP in white participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.14 mmHg (95% confidence interval (CI): -1.65 to -0.63), 5982 participants, 95 trials; DBP: MD + 0.01 mmHg (95% CI: -0.37 to 0.39), 6276 participants, 96 trials. Hypertension: SBP: MD -5.71 mmHg (95% CI: -6.67 to -4.74), 3998 participants,88 trials; DBP: MD -2.87 mmHg (95% CI: -3.41 to -2.32), 4032 participants, 89 trials (all high-quality evidence). The largest bias contrast across studies was recorded for the detection bias element. A comparison of detection bias low-risk studies versus high/unclear risk studies showed no differences. The effect of sodium reduction (from 195 to 66 mmol/day) on BP in black participants was as follows: Normal blood pressure: SBP: mean difference (MD) -4.02 mmHg (95% CI:-7.37 to -0.68); DBP: MD -2.01 mmHg (95% CI:-4.37, 0.35), 253 participants, 7 trials. Hypertension: SBP: MD -6.64 mmHg (95% CI:-9.00, -4.27); DBP: MD -2.91 mmHg (95% CI:-4.52, -1.30), 398 participants, 8 trials (low-quality evidence). The effect of sodium reduction (from 217 to 103 mmol/day) on BP in Asian participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.50 mmHg (95% CI: -3.09, 0.10); DBP: MD -1.06 mmHg (95% CI:-2.53 to 0.41), 950 participants, 5 trials. Hypertension: SBP: MD -7.75 mmHg (95% CI:-11.44, -4.07); DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15), 254 participants, 8 trials (moderate-low-quality evidence).   During sodium reduction renin increased 1.56 ng/mL/hour (95%CI:1.39, 1.73) in 2904 participants (82 trials); aldosterone increased 104 pg/mL (95%CI:88.4,119.7) in 2506 participants (66 trials); noradrenalin increased 62.3 pg/mL: (95%CI: 41.9, 82.8) in 878 participants (35 trials); adrenalin increased 7.55 pg/mL (95%CI: 0.85, 14.26) in 331 participants (15 trials); cholesterol increased 5.19 mg/dL (95%CI:2.1, 8.3) in 917 participants (27 trials); triglyceride increased 7.10 mg/dL (95%CI: 3.1,11.1) in 712 participants (20 trials); LDL tended to increase 2.46 mg/dl (95%CI: -1, 5.9) in 696 participants (18 trials); HDL was unchanged -0.3 mg/dl (95%CI: -1.66,1.05) in 738 participants (20 trials) (All high-quality evidence except the evidence for adrenalin). AUTHORS' CONCLUSIONS: In white participants, sodium reduction in accordance with the public recommendations resulted in mean arterial pressure (MAP) decrease of about 0.4 mmHg in participants with normal blood pressure and a MAP decrease of about 4 mmHg in participants with hypertension. Weak evidence indicated that these effects may be a little greater in black and Asian participants. The effects of sodium reduction on potential side effects (hormones and lipids) were more consistent than the effect on BP, especially in people with normal BP.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

BACKGROUND: In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved. OBJECTIVES: To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles. SELECTION CRITERIA: Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two review authors independently collected data, which were analysed with Review Manager 5.3. MAIN RESULTS: A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence. Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence. Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0.08; P =0.06); three studies, 393 participants. Moderate-quality evidence.White people with hypertension: SBP: MD -5.51 mmHg (95% CI: -6.45 to -4.57; P < 0.00001); 84 studies, 5925 participants; DBP: MD -2.88 mmHg (95% CI: -3.44 to -2.32; P < 0.00001); 85 studies, 6001 participants. High-quality evidence. Black people with hypertension: SBP MD -6.64 mmHg (95% CI:-9.00 to -4.27; P = 0.00001); eight studies, 619 participants; DBP -2.91 mmHg (95% CI:-4.52, -1.30; P = 0.0004); eight studies, 619 participants. Moderate-quality evidence. Asian people with hypertension: SBP: MD -7.75 mmHg (95% CI:-11,44 to -4.07; P < 0.0001) nine studies, 501 participants; DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15; P = 0.0006). Moderate-quality evidence.In plasma or serum, there was a significant increase in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.03), cholesterol (P < 0.0005) and triglyceride (P < 0.0006) with low sodium intake as compared with high sodium intake. All effects were stable in 125 study populations with a sodium intake below 250 mmol/day and a sodium reduction intervention of at least one week. AUTHORS' CONCLUSIONS: Sodium reduction from an average high usual sodium intake level (201 mmol/day) to an average level of 66 mmol/day, which is below the recommended upper level of 100 mmol/day (5.8 g salt), resulted in a decrease in SBP/DBP of 1/0 mmHg in white participants with normotension and a decrease in SBP/DBP of 5.5/2.9 mmHg in white participants with hypertension. A few studies showed that these effects in black and Asian populations were greater. The effects on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL: (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%).

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

BACKGROUND: In spite of more than 100 years of investigations the question of reduced sodium intake as a health prophylaxis initiative is still unsolved. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. SEARCH METHODS: PUBMED, EMBASE and Cochrane Central and reference lists of relevant articles were searched from 1950 to July 2011. SELECTION CRITERIA: Studies randomizing persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently collected data, which were analysed with Review Manager 5.1. MAIN RESULTS: A total of 167 studies were included in this 2011 update.The effect of sodium reduction in normotensive Caucasians was SBP -1.27 mmHg (95% CI: -1.88, -0.66; p=0.0001), DBP -0.05 mmHg (95% CI: -0.51, 0.42; p=0.85). The effect of sodium reduction in normotensive Blacks was SBP -4.02 mmHg (95% CI:-7.37, -0.68; p=0.002), DBP -2.01 mmHg (95% CI:-4.37, 0.35; p=0.09). The effect of sodium reduction in normotensive Asians was SBP -1.27 mmHg (95% CI: -3.07, 0.54; p=0.17), DBP -1.68 mmHg (95% CI:-3.29, -0.06; p=0.04). The effect of sodium reduction in hypertensive Caucasians was SBP -5.48 mmHg (95% CI: -6.53, -4.43; p<0.00001), DBP -2.75 mmHg (95% CI: -3.34, -2.17; p<0.00001). The effect of sodium reduction in hypertensive Blacks was SBP -6.44 mmHg (95% CI:-8.85, -4.03; p=0.00001), DBP -2.40 mmHg (95% CI:-4.68, -0.12; p=0.04). The effect of sodium reduction in hypertensive Asians was SBP -10.21 mmHg (95% CI:-16.98, -3.44; p=0.003), DBP -2.60 mmHg (95% CI: -4.03, -1.16; p=0.0004).In plasma or serum there was a significant increase in renin (p<0.00001), aldosterone (p<0.00001), noradrenaline (p<0.00001), adrenaline (p<0.0002), cholesterol (p<0.001) and triglyceride (p<0.0008) with low sodium intake as compared with high sodium intake. In general the results were similar in studies with a duration of at least 2 weeks. AUTHORS' CONCLUSIONS: Sodium reduction resulted in a 1% decrease in blood pressure in normotensives, a 3.5% decrease in hypertensives, a significant increase in plasma renin, plasma aldosterone, plasma adrenaline and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride. In general, these effects were stable in studies lasting for 2 weeks or more.