Количество значительно взаимодействующих с фуранокумаринами лекарственных средств растёт

"The number of drugs on the market with the potential to produce serious adverse and in many cases life-threatening effects when combined with grapefruit has markedly increased over the past few years from 17 to 43 in four years," said lead researcher David Bailey, from the Lawson Health Research Institute in London, Ontario.

Citrus fruits such as limes and Seville oranges, often used in marmalade, also contain the active ingredients -- called furanocoumarins -- that cause the dangerous interactions, the researchers said. The chemicals apparently inhibit an enzyme that normally deactivates about half the effects of medication.

More New Drugs a Bad Fit With Grapefruit, Study Finds

Применение статинов снижает риск возникновения депрессии у пациентов с ИБС

Background: Statins are among the most commonly prescribed medications worldwide. Although their benefits for cardiovascular disease are well established, the effects of statins on depressive symptoms are unknown.
Method: We examined the association between baseline statin use (2000–2002) and subsequent depressive symptoms in a prospective cohort study of 965 outpatients with coronary disease from 12 outpatient clinics in the San Francisco Bay Area. Depressive symptoms were assessed annually for 6 years using the Patient Health Questionnaire (PHQ) (primary outcome measure). We evaluated the cross-sectional association between statin use and risk of depressive symptoms at baseline and the longitudinal association between baseline statin use and risk of depressive symptoms during follow-up.
Results: Of the 965 participants, 629 (65%) used statins. At baseline, statin users had lower mean ± SE PHQ depression scores than nonusers (4.8 ± 0.2 vs 5.9 ± 0.3, P < .01). Statin users were less likely than nonusers to have depression (PHQ score ≥ 10) at baseline (17% vs 24%; P = .02) and during follow-up (28% vs 40%; P < .01). Among the 776 patients without depressive symptoms at baseline (PHQ < 10), statin use was associated with a 48% decreased odds of developing depression during follow-up (odds ratio [OR], 0.52; 95% CI, 0.38–0.73; P < .01). After we adjusted for potentially confounding variables, statin use remained associated with a 38% decreased odds of subsequent depression (adjusted OR, 0.62; 95% CI, 0.41–0.95; P = .02).
Conclusions: We found that statin use was associated with a decreased risk of subsequent depressive symptoms in patients with coronary heart disease. Whether use of statins prevents depressive symptoms deserves further study.

 Statin Use and Risk of Depression in Patients With Coronary Heart Disease: Longitudinal Data From the Heart and Soul Study

Когнитивное снижение при приёме статинов: распространенность и методы коррекции

DATA SYNTHESIS: Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected.
CONCLUSIONS: Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the current evidence does not support changing practice with respect to statin use, given this adverse effect.

 Is Statin-Associated Cognitive Impairment Clinically Relevant? A Narrative Review and Clinical Recommendations

Статины, холестерин и аффективные расстройства

New research into cholesterol-lowering statin drugs and serotonin-1A receptors may help explain the relationships between cholesterol levels and symptoms of anxiety and depression.

Shrivastava and colleagues1 explored the effect of chronic cholesterol depletion induced by mevastatin on the function and dynamics of the human serotonin-1A receptors stably expressed in animal cells. Statins are competitive inhibitors of HMG-CoA reductase, the key rate-limiting enzyme in cholesterol biosynthesis.

Statins, Cholesterol Depletion—and Mood Disorders: What’s the Link?

Низкий уровень холестерина как фактор риска аффективных расстройств

In the early 1990s several studies suggested a link between low cholesterol (< 160 mg/dL) and unnatural deaths, including suicide.2-4 Follow-up studies confirmed associations between low cholesterol and suicide attempts, especially violent ones.5 These associations are compelling given the neurobiologic effects of cholesterol, such as a net reduction of serotonergic function (Box 1). Low cholesterol may predispose an individual to aggression, impulsivity, and violence (Table 1).6 Many studies have found that patients with mood disorders have lower cholesterol levels;7 however, other research suggests they are at increased risk of hyperlipidemia, typically hypertriglyceridemia rather than hypercholesterolemia.

The neurobiologic effects of low cholesterol—particularly those related to serotonergic hypofunction—are thought to be mediate impulsive, aggressive, and violent behaviors that may predispose an individual to suicide.a,b The CNS contains one-fourth of the body’s free cholesterol,c which is synthesized primarily in situ.

Cholesterol improves membrane stability, reduces permeability, and may influence serotonergic function. Cholesterol depletion may impair function of 5-HT1A and 5-HT7 receptorsd,e and serotonin transporter activity.f Reduced cholesterol after treatment with simvastatin—an HMG-CoA reductase inhibitor that readily crosses the blood-brain barrier—resulted in acute (1-month) increases in serotonin transporter activity followed by subacute (>2 months) decreases.g Lower cholesterol levels may further decrease expression of serotonin receptors and cause a net reduction in serotonergic activity.

In addition, cholesterol is necessary for synapse formation and myelin production. Cholesterol depletion may have more diffuse effects on neurotransmission, such as gamma-aminobutyric acid receptors,hN-methyl-D-aspartate receptors,i opioid signaling,j and excitatory amino acids transport.k

Impulsivity associated with low serotonergic function and low total cholesterol has been suggested as a potential pathway for suicide.l Low cholesterol is associated with self-report measures of impulsivity;m however, increased impulsivity associated with lipid-lowering therapy may be temporary,n which is similar to the time-limited changes in serotonin transporter activity.g Human and animal data have suggested that low cholesterol may be linked to violent behaviors, including suicide.o

Multiple randomized controlled trials have not shown increased depression and suicide with use of lipid-lowering agents in healthy populations

Closely monitor individuals with mood disorders for changes in behavior or mental status after starting a lipid-lowering agent

Cholesterol, mood, and vascular health: Untangling the relationship

Лекарства снижающие уровень холестерина и депрессия

The scientists turned to the statin medication mevastatin to find out.

In lab tests using human serotonin receptors expressed in animal cells, they showed that long-term use of the drug caused significant changes in the structure and function of serotonin cell receptors.

Adding cholesterol to cells treated with mevastatin restored them to normal.

The results represent the first report describing the effect of long-term cholesterol depletion on this type of cell receptor and suggest that chronic, low cholesterol levels in the brain might trigger anxiety and depression, the scientists say.

Link Between Cholesterol Drug and Depression