Аспирин снижает риск депрессии у людей с повышенным уровнем гомоцистеина

High total plasma homocysteine (tHcy) is associated with increased risk of cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12) reduces tHcy by about 15%, but has equivocal effects on these health outcomes, suggesting that this relationship is either not causal or is confounded by other factors. The results of recent randomized trials suggest that antiplatelet therapy may confound these associations. This cross-sectional study assessed 3687 men aged 69–87 years for history of clinically significant depression (Geriatric Depression Scale 15 items 7) or a recorded diagnosis of depression in the Western Australian Data Linkage System, and collected information on the use of aspirin, B-vitamins and antidepressant medication, along with age, education, living arrangements, smoking history and medical comorbidity as assessed by the Charlson index. Participants donated a blood sample for the measurement of tHcy, and concentrations15 μmol l−1 were considered high. Five hundred and thirteen (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy, 41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic regression showed that high tHcy was associated with increased odds of depression (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20–2.14), as was the use of B-vitamins (OR=1.95, 95% CI=1.21–3.13). There was a significant interaction between high tHcy and aspirin use (OR=0.57, 95% CI=0.36–0.91), but not between high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26–2.46). The analyses were adjusted for smoking status, Charlson index and use of antidepressants. The results of this study indicate that older men with high tHcy who use aspirin have lower risk of depression, and suggest that antiplatelet therapy may be an effective preventive or management strategy for these cases. Randomized trials are required to confirm the antidepressant effect of aspirin in people with high tHcy.

Aspirin decreases the risk of depression in older men with high plasma homocysteine

Фолаты могут ослаблять негативную симптоматику у некоторых больных шизофренией

Folate supplementation appears to improve negative symptoms in schizophrenia patients, but only among those with a genetic variant of a folate-metabolizing enzyme, study results show.

It follows an earlier study by the same group showing that schizophrenia patients with low serum folate levels who were also homozygous for the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene had severe negative symptoms.

Folate may improve negative symptoms in some schizophrenia patients

Альтернативные методы лечения шизофрении

Outside of India, however, Sen and Bose's observations on the use of rauwolfia for psychotic disorders were generally ignored. It was not until 1954, when Nathan Kline2 reported that both whole root rauwolfia extract and reserpine—a purer preparation—seemed to be somewhat more effective than placebo in more than 400 inpatients with neuropsychiatric conditions, that clinicians in the West took notice. Although it soon became apparent that phenothiazines were generally more tolerable than reserpine, and even after our enthusiastic embrace of clozapine, a respected 1991 review3 still listed reserpine as 1 of 8 reasonable, evidence-based treatment options for persons affected with the refractory symptoms of schizophrenia.

Two essential omega-3 fatty acids were compared in a 3-month, double-blind pilot study that found that augmentation with eicosapentaenoic acid (EPA) was superior to docosahexaenoic acid (DHA) or placebo in significantly reducing Positive and Negative Syndrome Scale (PANSS) scores; a second study using EPA suggested that supplementation with omega-3 for extended periods can benefit some patients even without antipsychotics.

On the other hand, a 16-week trial in 87 patients that compared 3 g/d of e-EPA with placebo found no difference in positive, negative, mood, or cognitive symptoms of schizophrenia.26 Noting that both the active and placebo groups had improvements in their PANSS ratings, these investigators evaluated the placebo response in 37 study participants and found that the 9.5% improvement in the PANSS total score usually occurred by the end of the first 2 weeks of participation, which argues for the value of a placebo run-in phase for future studies.27

Revisiting the initial findings of plasma membrane abnormalities, a 24-hour dietary recall in 146 community-dwelling patients with schizophrenia found little difference in dietary fatty acid and antioxidant intake from controls.28 However, a more elaborate evaluation of 72 subjects with schizophrenia found that the previously reported membrane lipid abnormalities could be explained by the fact that many of the subjects were smokers and had a significantly different omega-3 dietary intake from that of the controls.

Sitting between mainstream and alternative therapies are amino acid treatments, derived from the recognition that phencyclidine (PCP) psychosis was a better model for schizophrenia than the previous model of amphetamine psychosis. Among other observations, those with PCP intoxication presented with negative as well as positive symptoms. The mechanism of PCP's action was eventually elucidated; it specifically blocked the ion channel in NMDA (N-methyl-d-aspartate) glutamate receptors in the brain. An allosteric modulatory site on this complex receptor has been referred to as the "glycine" site, and its endogenous ligands plausibly may be the amino acids glycine, d-serine, and d-alanine (the latter 2 unusual d-forms present in the brain because of a racemizing enzyme).

A meta-analysis of short-term clinical trials found that treatment augmented with the agonists glycine and d-serine moderately reduced negative symptoms, while partial agonist d-cycloserine was less efficacious.35 These agents do not appear helpful for patients treated with clozapine, although glycine and d-serine may be effective for those being treated with olanzapine or risperidone.

High homocysteine levels have been found to interfere with NMDA receptors in animal studies. Neeman and coauthors46 reported finding lower plasma glycine levels and higher homocysteine levels in patients with schizophrenia compared with controls, and glycine levels correlated with increased negative symptoms. Findings of higher homocysteine levels in patients with schizophrenia may often involve folate-deficient dietary choices, obesity, or cigarette smoking, but one study found that these variables explained relatively little of the high homocysteine levels

Oxidative stress/free radical damage has been proposed as mediating pathology in various neuropsychiatric disorders, including schizophrenia. Small initial trials failed to shed adequate light on the value of ascorbic acid (vitamin C) in the treatment of schizophrenia,49,50 although a recent 8-week study reported significant improvement in Brief Psychiatric Rating Scale scores for those receiving an adjunctive 500 mg/d dosage of vitamin C.51 In addition, one study25 with positive findings used adjunctive omega-3 with vitamins C and E. Additional studies are needed to evaluate this approach.

Another putative adjunctive antioxidant strategy in schizophrenia involves the addition of EGb, a standardized Ginkgo biloba extract. Although several studies have shown fairly consistent preliminary results,52-54 larger and more definitive studies are still needed.

The higher rates of schizophrenia in those born in winter or spring, and the reported association between prenatal exposure to the 1945 famine of the "Dutch Hunger Winter" and later development of schizophrenia in offspring may be rationalized by the hypothesis that schizophrenia is more prevalent in those who have had vitamin D deficiency during the first year of life. The results of a 1966 study of a Finnish-birth cohort lend support to this theory.63 However, as there were very few children not given the then-recommended vitamin D supplement, and since not receiving the supplement may have been associated with other plausible risk factors, this single study provides only weak support for this interesting idea.

Treatment Resistance in Schizophrenia: The Role of Alternative Therapies

Пернициозная анемия в форме кататонии без признаков анемии и макроцитоза

Pernicious anaemia can present with psychiatric symptoms before haematological or neurological manifestations appear. We describe a young woman who presented with insidious onset catatonia without evidence of psychosis or depression. Blood count and mean cell volume were normal and neurological findings were equivocal. Low B12 levels and intrinsic factor antibodies were found only by chance when they were included in a battery of further investigations. B12 replacement was followed by prompt improvement. This case provides an argument for wider screening for B12 deficiency in certain individuals with psychiatric disorders.

Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis

Роль L-метилфолата в терапии депрессивных расстройств

Folate is a water soluble B vitamin (B9), considered one of the 13 essential vitamins. The primary function of folate is the transfer of methyl and formyl groups, thus, it is essential for cell growth and reproduction, the breakdown and utilization of proteins, the formation of nucleic acids, red blood cell maturation, and a variety of CNS reactions. Dihydrofolate is the dietary form found in orange juice, spinach, asparagus, beans, liver, yeast, whole grain cereals, and eggs. Folic acid is the synthetic form of folate in over-the-counter vitamins and used to fortify the food supply (to help prevent neural tube defects, the FDA mandated folic acid fortification of flour in 1998). Folic acid is also the predominant form used in prescription strength prenatal vitamins. Both folic acid and dihydrofolate are not biologically active forms of folate, but are essentially pro-drugs, and must undergo enzymatic transformation to L-methylfolate in order to be used by cells, and unlike other forms of folate, L-methylfolate readily crosses the blood-brain barrier for use in the CNS.


Almost 85% of dietary folate and nearly all supplemental folic acid is absorbed into the venous system in the proximal small intestine. The enzymatic conversion begins in the intestinal wall—it is a three step process for dihydrofolate, and a four step process for folic acid (Slide 3). Folic acid is converted to dihydrofolate (DHF) by dihydrofolate reductase enzyme (DHFR), and DHF is then converted to tetrahydrofolate (THF). The conversion of THF to 5,10-methyleneTHF follows. Finally, the conversion of 5,10-methyleneTHF to L-methylfolate is achieved by the methyltetrahydrofolate reductase enzyme (MTHFR). This last step completes the four step transformation process by which the bioactive cofactor, L-methylfolate, is made available to the brain to be used in the synthesis of monoamine neurotransmitters associated with mood regulation (serotonin, norepinephrine, and dopamine).

There are five trials that examine folate therapy in depressive disorders. In a study59 with patients who had low or borderline low RBC folate, depressed patients on tricyclic antidepressants or MAOIs were augmented with methylfolate 15 mg (L-methylfolate 7.5 mg) experienced significantly greater clinical improvement and social improvement at 3 months (P<.02) and 6 months (P<.01) compared to patients treated with antidepressants alone. The methylfolate-augmented patients continued to improve for 6 months compared to patients augmented with placebo, and none experienced relapse. In a separate double-blind, controlled trial60 comparing methylfolate 50 mg/day to trazodone 100 mg/day, depressed patients experienced a significant decrease in HAM-D scores at 4 and 8 weeks in both groups, with response rates in the methylfolate group at 45%, and in the trazodone group (not statistically significant) at 29%.


An open label trial61 of methylfolate as monotherapy in elderly depressed subjects demonstrated an 81% response rate (>50% reduction in HAM-D) by 6 weeks of therapy. A second monotherapy study examined a depressed population of 36 chronic alcoholics. After a week of placebo wash-out, subjects received 4 weeks of 90 mg methylfolate therapy. This dosing (30 mg TID) significantly improved depressive symptoms based on the HAM-D scale with the majority reporting improved mood and less fatigue (P<.01).62 Alpert and colleagues63 conducted an open label trial augmenting selective serotonin reuptake inhibitor (SSRIs) with folinic acid in patients who had failed at least 4 weeks of SSRI therapy. The response to folinic acid was not robust (P<.01, n=22), but it was well tolerated overall.

The standard dose of L-methylfolate for the augmentation of antidepressants is one 7.5 mg tablet/day. No titration is necessary, and it is not associated with withdrawal symptoms at discontinuation. The maximum amount of L-methylfolate that can be absorbed in one dose is ~15 mg.67 If more than one 7.5 mg tablet/day is needed, it may be prudent to give in divided doses. All reported adverse events occur at placebo rates or lower, and overall it is an extremely well tolerated agent, allowing patients to continue L-methylfolate therapy as long as necessary to maintain remission. There are no known contraindications and no known drug interactions.

The Role of L-methylfolate in Depressive Disorders

Сосудистая деменция: фармакотерапия

Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid, as well as such nonpharmacological approaches as validation therapy.

From the studies reviewed here, one may draw several conclusions. First, there are relatively few studies on vascular dementia treatment and no compound has been approved by any regulatory body for treatment of vascular dementia. Second, it appears that there are several compounds with different mechanisms of action that show mild efficacy in improving cognition and even ADLs in patients with vascular dementia. Third, there is one compound (memantine) that has been suggested to act within the confines of the current excitotoxic cell death model, although direct evidence confirming this hypothesis is still lacking. Overall, one could easily conclude that a number of different mechanisms may be at play in ethiopathogenesis of vascular dementia. Vascular conditions aside, nerve cell resistance to injury and our efforts to manipulate it still remains a conundrum, which will require new technologies to solve.

Vascular dementia: Pharmacological treatment approaches and perspectives

коррекция акатизии вызванной нейролептиками при помощи пиридоксина

his study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design.

The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037).
Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia: A Randomized, Double-Blind, Placebo-Controlled Study.

шизофреноподобный психоз вследствие дефицита цианокобаламина

Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.
Schizophrenia-like psychotic episode precipitated by cobalamin deficiency.

депрессия и фолиевая кислота

Instead, the men were referring to medical foods - more specifically, a new product called Deplin, a medical food that includes L-methylfolate, the only active form of folate that can cross the blood brain barrier and help with the synthesis of the neurotransmitters associated with mood and, consequently, mood disorders such as depression: serotonin, dopamine, and norepinephrine.

Research shows that people with depression and low folate levels are less likely to respond to treatments such as antidepressants and less likely to achieve remission.

Treating Depression and Folate Deficiency With Medical Foods