Микрофлора кишечника и депрессия

Abstract

Purpose of review With depressive disorders the leading source of disability globally, the identification of new targets for prevention and management is imperative. A rapidly emerging field of research suggests that the microbiome–gut–brain axis is of substantial relevance to mood and behaviour. Similarly, unhealthy diet has recently emerged as a significant correlate of and risk factor for depression. This review provides evidence for the gut microbiota as a key factor mediating the link between diet and depressive illness.

Recent findings The development of new technologies is affording a better understanding of how diet influences gut microbiota composition and activity and how this may, in turn, influence depressive illness. New interventions are also suggesting the possible utility of pre and probiotic formulations and fermented food in influencing mental health.

Summary Although in its early stages, the emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans. The recognition that the gut microbiota interacts bidirectionally with other environmental risk factors, such as diet and stress, suggests promise in the development of interventions targeting the gut microbiota for the prevention and treatment of common mental health disorders.

The Gut Microbiome and Diet in Psychiatry: Focus on Depression

Оланзапин превзошел ламотриджин в профилактике депрессивной фазы биполярного аффективного расстройства

Background

Bipolar disorder is a highly recurrent disease and has great impact on the function of patients. Depressive symptoms consist of more than 50% of life time during the illness and may lead to self harm or suicidal behaviors. Little is known about the antidepressant effects of olanzapine, an atypical antipsychotic, as monotherapy despite its indication for preventing manic episodes. In contrast, lamotrigine, a mood stabilizer, has been proven to be effective in preventing depression in patients with bipolar disorder. However, no studies have compared the efficacy between lamotrigine and olanzapine in the maintenance treatment of bipolar disorder. This enriched naturalistic study was implemented to assess the effectiveness of olanzapine and lamotrigine as monotherapy in the prevention of recurrence of bipolar disorder.

Methods

Patients with bipolar disorder in a euthymic state (Young's Mania Rating Scale (YMRS) score < 12, and 21-item Hamilton Depression Rating Scale (HAM-D) score < 7) for at least two months, having already received either olanzapine or lamotrigine as the maintenance treatment were recruited. The patients maintained with olanzapine (n = 22) were applied to olanzapine group whereas those maintained with lamotrigine (n = 29) were applied to lamotrigine group. They were followed up for 12 months. Differences in the efficacy between olanzapine and lamotrigine in recurrence prevention were analyzed. The Kaplan-Meier method was used to generate time-to-recurrence curves, and differences between the two groups were compared using the log-rank test.

Results

Olanzapine had a significantly lower recurrence rate of depressive episodes than lamotrigine (20.0% vs. 57.7%, chi2 = 6.62, p = .010). However, olanzapine and lamotrigine had similar mania (15.0% vs. 0%, chi2 = 4.17, p = .075, Fisher's exact test) and any mood episode (35.0% vs. 57.7%, chi2 = 2.33, p = .127) recurrence rates. Olanzapine was significantly superior to lamotrigine in the time to recurrence of depressive episodes (chi2 = 4.55, df = 1, p = .033), but there was no difference in the time to recurrence of any mood episode (chi2 = 1.68, df = 1, p = .195).

Conclusions

This prospective naturalistic study suggests that olanzapine is more effective than lamotrigine in the prevention of depressive episodes in patients with bipolar disorder. Future large-scale randomized studies are warranted to validate our results.

 Olanzapine is superior to lamotrigine in the prevention of bipolar depression: a naturalistic observational study

Перспективные методы лечения депрессий

Long-term stress harms cells in the brain and body. Stressful experiences are believed to be closely associated with the development of psychological alterations and, thus, neuropsychiatric disorders.
In conditions of chronic stress exposure, nerve cells in the hippocampus begin to atrophy. (The hippocampus is a part of the brain involved with emotions, learning, and memory formation.)
The new depression theories “should not be viewed as separate entities because they are highly interconnected,” researchers write.
“Integrating them provides for a more expansive understanding of the pathophysiology of depression and biomarkers that are involved.”
Such biomarkers are molecules in the body that can be indicators of depression. The authors identify more than a dozen potential biomarkers depression, including monoamine regulators; proinflammatory cytokines and other inflammatory mediators; mediators of glutaminergic activity and GABAergic activity; and regulators of neurogenesis.
A bevy of new depression treatments are currently offered or on the horizon include corticotropin-releasing hormone antagonists; dexamethasone; partial adrenalectomy; long-term cognitive behavioral therapy; ketamine and other NMDA antagonists. Other treatments include benzodiazepines; anesthetics; deep brain stimulation; transcranial magnetic stimulation; exogenous brain-derived neurotrophic factor; selective serotonin reuptake inhibitors; tricyclic antidepressants; atypical antidepressants; reduction in inflammation; and anti-inflammatory drugs.

 Beyond Antidepressants: Taking Stock of New Treatments

Роль воспалительных процессов в формировании резистентности к лечению депрессии

Inflammation may also be relevant to depression prevention and relapse. There are multiple clinical factors associated with both inflammation and TRD that can be addressed through lifestyle changes. Treating obesity with diet and exercise in patients with increased inflammation is a primary example. In a recent clinical trial of partial treatment responders, depressed patients with increased TNF levels were more likely to respond to an add-on exercise intervention than were patients who were partially responsive to an SSRI. Another consideration is behavioral stress management including compassion meditation training, which has been shown to reduce inflammatory responses to a laboratory psychosocial stressor.

Exercise and meditation have been associated with an increased parasympathetic tone, which, in turn, has been associated with decreased inflammatory tone. These effects are likely related to parasympathetic activation of T cells that produce acetylcholine that binds to the α subunit of the nicotinic acetylcholine receptor, leading to inhibition of NF-κB.41 Finally, optimizing the management of medical illnesses associated with inflammation may also reduce depression symptoms and improve treatment response.

Inflammation and Treatment Resistance in Major Depression: The Perfect Storm

Возможные механизмы антидепрессивного действия антипсихотиков второго поколения

Although the exact mechanism of SGAs for MDD has not yet been clearly elucidated, several plausible underlying mechanisms are listed as follows: modulation of crucial neurotransmitter receptors and transporters such as dopamine, serotonin and noreinephrine resulting in net effect of enhancement of such neurotransmitters' transmission, effects on sleep, alteration of various hormones (ACTH, sex hormones, etc.), modification of immune functions including modulation of inflammation process (cytokines, etc.), antioxidation process and modulation of neurotrophic factors (BDNF, etc).[13]

Specifically, the main pharmacological rationale of SGAs as an antidepressant augmentation would be based on their effects on monoamine transporters or receptors of crucial neurotransmitters such as serotonin, norepinephrine and dopamine, which are also the main target of contemporary antidepressants. The partial agonism at D2 and/or D3 receptors may increase dopamine neurotransmission at the prefrontal cortex. The increase in the dopamine concentration in the prefrontal cortex may be also indirectly related to the antidepressive effect of 5-HT1A receptor agonist.[14,15] The antidepressant effect may also be mediated by 5-HT1A partial agonism and/or antagonism at 5-HT2A receptors.[16–18] Although, still controversial, the antidepressant effect of 5-HT1A receptor agonists may be predominantly mediated by postsynaptic 5-HT1A receptors, while the anxiolytic effect would be mainly associated with presynptic 5-HT1A receptors.[19] The antagonism of the 5-HT2C receptors has been also found to be involved in increased dopamine and norepinephrine transmission.[20] It is also well known that high affinity at the α2-adrenergic receptor may enhance the release of norepinephrine.[21] Unlike any other SGAs, ziprasidone was reported to block synaptic serotonin, norepinephrine and dopamine reuptake in vitro.[22,23] Evidence indicates that both 5-HT6 agonists and antagonists may evoke identical responses in animal models of MDD, although the possible mechanisms of these effects seem to be diverse and are not clearly understood. The augmented effects were notable by combining antidepressants with a selective 5-HT6 receptor antagonist.[24] There is also a considerable amount of evidence supporting a role for the 5-HT7 receptor in MDD. The blockade of the 5-HT7 receptor led to antidepressant-like effects in animal models of MDD. It should be also worthy to mention that augmentation of 5-HT7 receptor antagonists with antidepressants was remarkable in animal models of MDD.[25]

Another mechanism involving in the action of SGAs should be the alteration of the glutamate receptor activity, and thus restoring normal glutamatergic neurotransmission and reducing the chances of excitotoxicity.[26] Some SGA treatment may also cause a decrease in plasma adrenocorticotropic hormone concentration and a normalization of HPA-axis dynamics.[27] An impaired neuroprotection has also been implicated in the pathophysiology of MDD.[28,29] Interestingly, activation of the 5-HT1A receptors was shown to be neuroprotective against various brain insults such as N-methyl-daspartic acid.[30] Some SGAs have also demonstrated such neuroprotective effects indicating a potential role in the protection against excitotoxicity in vivo.[30]

Overall 5-HT2A antagonism should be a commonly shared biological relevance for most of the SGAs as a potential mechanism of their antidepressant effect. Interactive effects with the dopaminergic system may be more distinct with the action mechanism of amisulpride and aripiprazole, while norepinephrine- and/or serotonin-reuptake inhibition should be the unique case with quetiapine or ziprasidone.[31] Each antipsychotic has a distinct profile of affinities towards different neurotransmitter receptors, which should be associated mainly with mediation of antidepressant-like effects.

Second-generation Antipsychotics in the Treatment of Major Depressive Disorder

Упражнения, депрессии, цитокины

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (P < 0.0001). In addition, a significant positive correlation between change in IL-1β and change in depression symptom scores was observed (P = 0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1β to positive depression treatment outcomes.

 Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder

ЭСТ в сравнении с антидепрессивным эффектом анестезии изофлюраном

Deep-inhalation isoflurane anesthesia has an antidepressant effect that approaches the effect of electroconvulsive therapy (ECT), with fewer cognitive side effects, preliminary results indicate.

Anesthetic a Better Alternative to ECT in Resistant Depression?

Механизм неврологических побочных эффектов сульфаниламидов

The team drew from previous research showing that blocking the activity of a certain enzyme (sepiapterin reductase) affects the levels of an important molecule called tetrahydrobiopterin (BH4) in cells. BH4 is critical for the production of neurotransmitters like serotonin and dopamine, and BH4 deficiency causes similar neurological problems to those associated with sulfonamide side effects. 

The EPFL scientists showed for the first time that sulfonamides actually bind to the part of the enzyme that makes BH4. Using a high-throughput drug screening system, the researchers identified ten sulfonamides that strongly inhibit the enzyme. Taking advantage of the expertise of Florence Pojer at EPFL's Global Health Institute, the scientists were able to solve the enzyme's molecular structure and determine how sulfonamides bind to it.

 New Understanding Of The Neurological Side Effects Of Sulfonamide Antibiotics

Физические упражнения в терапии депрессии

Based on research, aerobic exercise is the preferred form of exercise for patients with major depression. There is also some research support for resistance training, said Rethorst and Trivedi.

Researchers suggest that patients participate in three to five exercise sessions per week, for 45 to 60 minutes per session. In terms of intensity, for aerobic exercise, they recommend achieving a heart rate that is 50 to 85 percent of the individual’s maximum heart rate.

For resistance training, they recommend a variety of upper and lower body exercises — three sets of eight repetitions at 80 percent of the maximum weight that the person can lift one time.

The findings suggest that patients may experience a relief in depression in as little as four weeks after starting exercise. However, Rethorst and Trivedi emphasize that the exercise regimen should be continued for at least 10 to 12 weeks to achieve the greatest antidepressant effect.

Although some people question whether patients with MDD would actually participate in an exercise program, the studies reveal that only about 15 percent of patients dropped out of the exercise programs — comparable to dropout rates in studies of medications and psychotherapy.

New Guidelines for Using Exercise as an Antidepressant

Ламотриджин при униполярной депрессии

On the basis of currently available evidence, clinicians are urged to not prescribe lamotrigine for MDD. If a detailed and thorough clinical evaluation finds no specific evidence of bipolar disorder (mania or hypo­mania) in a particular patient, it is not appropriate to prescribe lamotrigine for that patient, since there is no evidence that that particular patient has bipolar disorder.

 Lamotrigine for Major Depressive Disorder Is Inappropriate

Целесообразность потенцирования атипичными антипсихотиками при депрессии

For the study, researchers reviewed 14 previous randomized clinical trials in which the combined use of an antidepressant and an antipsychotic medication were compared to the use of an antidepressant with a placebo.

The medications investigated in the studies were aripiprazole (Abilify), olanzapine/fluoxetine (Symbyax), quetiapine (Seroquel) and risperidone (Risperdal).

The results showed a small benefit with antipsychotic use on relieving the symptoms of depression. But when the researchers looked for a more meaningful outcome — whether the patients’ quality of life had improved — no benefit was found.

...

Antipsychotic medications were associated, however, with more negative side effects, including weight gain, akathisia (a feeling of restlessness), sleepiness and abnormal results from cholesterol and other metabolic-related laboratory tests.

In another study, British researchers found strong evidence that engaging in talk therapy was an effective add-on to antidepressants.

The findings showed that antidepressant-resistant patients who received cognitive behavioral therapy in addition to an antidepressant experienced both a significant reduction in their depression and a significant improvement in their quality of life.

Adding Antipsychotic Meds to Antidepressants Shows Risk, Little Benefit

Комбинация эсциталопрама с арипипразолом в терапии коморбидной депрессии алкогольной зависимости

 The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 ( F=13.1, p < 0.01 ). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.

Adjunctive aripiprazole therapy with escitalopram in patients with co-morbid major depressive disorder and alcohol dependence: Clinical and neuroimaging evidence

Эффективность сочетания холекальциферола с флуоксетином

Objective: To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder.
Methods: In the present double-blind, randomized, placebo-controlled trial, 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were randomly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks. Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale (HDRS) as a primary outcome measure and the 21-item Beck Depression Inventory (BDI) as a secondary outcome measure. Serum 25(OH) vitamin D was measured at baseline and after intervention.
Results: Forty patients completed the trial. A two-way repeated-measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention, with a significant difference between the two groups. The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment.
Conclusions: In the present 8-week trial, the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms.

 Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder

Случай злоупотребления кока-колой в рамках депрессии

BACKGROUND: Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature.
CASE PRESENTATION:
The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared.
CONCLUSION:
This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient's symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

 A case of cola dependency in a woman with recurrent depression.

Скополамин и циталопрам в терапии депрессии

Evidence is accumulating that cholinergic pathways in the brain help to regulate mood, and researchers have shown that intravenous scopolamine (an anticholinergic) is effective for moderate-to-severe depression (JW Psychiatry Mar 29 2010). This 6-week, Iranian, double-blind study tested whether oral scopolamine (0.5 mg twice daily), added to citalopram as an initial treatment produces greater antidepressant effects than citalopram plus placebo. Participants were 40 patients with moderate-to-severe major depression (baseline score on the 17-item Hamilton Rating Scale for Depression, 22).
At days 4, 28, and 42, patients receiving scopolamine augmentation had significantly greater reduction in symptoms than patients taking add-on placebo, with an overall large effect size (0.9). Response rates were higher with scopolamine than placebo at week 4 (65% vs. 30%) but not at week 6. Remission rates for scopolamine-treated patients were higher at week 6 (65% vs. 20%). Dry mouth, dizziness, and blurred vision were each noted by at least 40% of scopolamine recipients.
Comment: This study shows that scopolamine given orally (a much preferable route of administration for routine clinical practice) adds significantly to the effect of a selective serotonin reuptake inhibitor for initial treatment of moderate-to-severe depression, although whether it is worth the side effect burden is unclear. Unfortunately, we also do not know whether scopolamine would benefit patients with treatment-resistant depression, although this study's effects in relatively severe depression suggest that such a trial might be pursued. The study's high rate of placebo response (but not remission) and the absence of formal cognitive testing compromise the generalizability of the findings.

Oral Scopolamine Augmentation for Major Depression

Употребление витамина D3 не проявило эффективности в предупреждении депрессии у людей с низким уровнем 25-гидроксивитамина D

Aims

To compare depressive symptoms in participants with low and high serum 25-hydroxyvitamin D (25(OH)D) levels and to examine whether supplementation with vitamin D3 would improve symptoms in those with low serum 25(OH)D levels.

Method

Participants with low 25(OH)D levels were randomised to either placebo or 40 000 IU vitamin D3 per week for 6 months. Individuals with high serum 25(OH)D levels were used as nested controls. Depressive symptoms were evaluated with the Beck Depression Inventory, Hospital Anxiety and Depression Scale, Seasonal Pattern Assessment Scale and Montgomery–Åsberg Depression Rating Scale. The study was registered at ClinicalTrials.gov(NCT00960232).

Results

Participants with low 25(OH)D levels (n = 230) at baseline were more depressed (P < 0.05) than participants with high 25(OH)D levels (n = 114). In the intervention study no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo.

Conclusions

Low levels of serum 25(OH)D are associated with depressive symptoms, but no effect was found with vitamin D supplementation.

 Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case–control study and randomised clinical trial

Антидепрессивные свойства оланзапина

Background

Atypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored.

Aims

To evaluate olanzapine monotherapy in patients with bipolar depression.

Method

Patients with bipolar depression received olanzapine (5–20 mg/day, n = 343) or placebo (n = 171) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery–Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global Impression – Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (50% reduction in MADRS at end-point), recovery (MADRS 12 for 4 weeks plus treatment completion) and remission (MADRS 8). The trial was registered with ClinicalTrials.gov (NCT00510146).

Results

Olanzapine demonstrated: significantly greater (P < 0.04) improvements on MADRS (least-squares mean change –13.82 v. –11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P⩽0.05) more response and remission, but not recovery; significantly (P < 0.01) greater mean increases in weight, fasting cholesterol and triglycerides; and significantly more (P < 0.001) patients gained ⩾7% body weight.

Conclusions

Olanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

 Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression*

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

Целесообразность применения монотерапии кветиапином для лечения депрессии

Background

Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.

Objectives

This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.

Data sources

MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression.

Study eligible criteria, participants and interventions

Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.

Study appraisal and synthesis methods

All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.

Results

A total of 1497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as >= 50% reduction of the MADRS total score and the MADRS total score of <=8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].

Limitations

Variety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.

Conclusions

Based on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted.

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

 

Позднее начало лечения депрессии ассоциировано с худшим ответом на терапию

Background

The duration of untreated illness has been considered a likely predictor of the course of psychotic disorders. However, there is only sparse data concerning the influence of treatment delay on the outcome of mood disorders. The present study aimed to assess the effect of prolonged untreated depression on the outcome of antidepressant treatment.

Method

Patients aged 18–70 years with recent onset of the first lifetime depressive episode were systematically recruited by the Danish Psychiatric Central Research Register during a 2-year period. A total number of 399 individuals out of 1006 potential participants in the Register were interviewed, and 270 fulfilled the inclusion criteria. The validity of the diagnosis, duration of untreated illness, remission on first-line antidepressant treatment and a number of covariates, including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, and family history of psychiatric illness, were assessed by structured interviews.

Results

The remission rate was significantly decreased among patients with six months or more of untreated depression as compared to patients who were treated with antidepressant medication earlier after onset (21.1% versus 33.7%, OR=0.5, 95% CI 0.3 to 0.9, p=0.03). The negative influence of a prolonged DUI on the outcome did not seem confounded by any of a wide range of demographic and clinical variables.

Limitations

The outcome was evaluated retrospectively. The findings cannot be generalized to patients outside hospital settings.

Conclusion

Initiation of antidepressant treatment more than six months after onset of first episode depression reduces the chance of obtaining remission. The results emphasize the importance of early recognition and treatment of patients suffering from depression.

The effect of prolonged duration of untreated depression on antidepressant treatment outcome