Витамин D

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Lurasidone Demonstrated Efficacy In Treating Patients - phase 3 study

Lurasidone 40 and 120 mg, taken once-daily, demonstrated significantly greater improvement versus placebo on the primary efficacy measure, the Positive and Negative Syndrome Scale (PANSS) total score, at study endpoint. PANSS score changes from baseline for lurasidone 40 and 120 mg/day versus placebo were -25.7 and -23.6 vs. -16.0, respectively, at study endpoint. A total of 53% of patients on lurasidone 40 mg/day and 47% of patients on lurasidone 120 mg/day demonstrated a 30% or more improvement on the PANSS total score from baseline versus 38% on placebo.

The effect of lurasidone on weight was similar to placebo, median weight change: 0.9 kg (2 lbs) for 40 mg/day, 0.5 kg (1.1lbs) for 120 mg/day vs. 0 kg for placebo at study endpoint. The incidence of clinically significant weight gain (greater than or equal to 7% increase from baseline to study endpoint) was 7.6% for lurasidone 40 mg/day, 4.2% for lurasidone 120 mg/day and 7.0% for placebo.

Lurasidone was also well-tolerated with an overall discontinuation rate similar to placebo (40% vs. 39% placebo) and few adverse event-related discontinuations (9% for both the overall lurasidone group and placebo). Adverse events seen in the trial were generally mild. The most commonly reported adverse events for lurasidone 40 and 120 mg/day combined (greater than 5% and at least twice the rate of placebo) were akathisia (17.3% vs. 0.9% placebo), somnolence (12.2% vs. 4.3% placebo), sedation (11.4% vs. 3.4% placebo), parkinsonism (10.1% vs. 1.7% placebo), nausea (9.3% vs. 4.3% placebo), and dystonia (5.5% vs. 0.9% placebo).

Lurasidone is an atypical antipsychotic discovered and developed by DSP with a unique chemical structure. Lurasidone has high affinities for dopamine D2, serotonin 5-HT7, 5-HT2A, 5-HT1A, and noradrenalin alpha2C receptors and minimal-to-no affinity for histamine H1 or cholinergic M1 receptors.

Thread: Lurasidone Demonstrated Efficacy In Treating Patients - phase 3 study

Комбинация сертралина с оланзапином в терапии психотической депрессии

At the conclusion of the 12-week trial, investigators found that treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio, 1.28; 95% confidence interval, 1.12 – 1.47; P < .001) and that 49% of subjects in the combination therapy group were in remission at their last assessment vs 23.9% of those treated with olanzapine alone.

In addition, the study showed that combination therapy was comparably superior in both younger and older age groups. Although both age groups experienced significant increases in cholesterol and triglyceride concentrations, statistically significant increases in glucose occurred in younger adults.

Further, whereas both age groups experienced weight gain, younger adults gained significantly more weight than their older counterparts — a mean gain of 6.5 vs 3.3 kg.

The study findings suggest that combination therapy is effective and offers physicians and their patients a viable alternative to electroconvulsive therapy, which is generally considered the treatment of choice for this condition but is not without challenges.

The researchers note that although bilateral electroconvulsive therapy has a response rate of 87% when administered in academic centers, the response when delivered in the community setting is much lower, ranging from 30% to 47%. Further, they add, pharmacological treatment may be more practical and less stigmatizing for patients.

STOP-PD: Combination Therapy With Sertraline Plus Olanzapine Effective in the Treatment of Psychotic Depression

Комбинирование клозапина с ламотриджином

Schizophrenia patients routinely are treated with polypharmacy--often with antidepressants or anticonvulsants--in attempts to improve negative symptoms, aggression, and impulsivity. Most adjuncts, however--including divalproex, antidepressants, and lithium--have shown very small, inconsistent, or no effects. The only agent with a recent meta-analysis supporting its use as augmentation in treatment-resistant schizophrenia is lamotrigine, an anticonvulsant approved for use in epilepsy...

Clozapine Augmentation with Lamotrigine

Fatty Acid's Role in Alzheimer's Remains In Doubt

An omega-3 fatty acid (DHA) did not slow Alzheimer's, but it may help with prevention and sharpen the memories of seniors with normal age-related memory complaints.

The findings of this study "indicate that the use of 900 mg of . . . DHA per day improves learning and memory recall in healthy aging adults with mild memory complaints

Fatty Acid's Role in Alzheimer's Remains In Doubt

Neurobiological mechanisms in major depressive disorder

нейропсихиатрические расстройства и токсоплазмоз

Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed. Copyright (c) 2009 S. Karger AG, Basel.

pubmed

Миртазапин в качестве корректора акатизии вызванной антипсихотиками

OBJECTIVE: To evaluate the role of mirtazapine in the treatment of antipsychotic-induced akathisia. DATA SOURCES: MEDLINE (1966-February 2008) and PsycINFO (1967-February 2008) were searched using the terms akathisia and mirtazapine. A bibliographic search was conducted as well. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the search were evaluated. All primary literature was included in the review. DATA SYNTHESIS: Antipsychotic-induced akathisia can be difficult to manage and may respond to mirtazapine based on its antagonist activity at the serotonin 5-HT(2A)/5-HT(2C) receptors. Three case reports (N = 9 pts.), 1 placebo-controlled trial (N = 26), and 1 placebo- and propranolol-controlled study (N = 90) that evaluated mirtazapine for antipsychotic-induced akathisia have been published. Mirtazapine demonstrated a response rate of 53.8% compared with a 7.7% response rate for placebo, based on at least a 2-point reduction on the Barnes Akathisia Scale (global subscale; p = 0.004). Using the same criterion, mirtazapine and propranolol demonstrated efficacy based on response rates of 43.3% and 30.0% compared with placebo (6.7%; p = 0.0051). Mirtazapine was better tolerated than propranolol. In both studies, drowsiness was the most common adverse event associated with mirtazapine. CONCLUSIONS: Mirtazapine may be considered a treatment option for antipsychotic-induced akathisia. It may be especially useful for patients with contraindications or intolerability to beta-blockers and for those with comorbid depression or negative symptoms. Additional studies should be conducted to provide further evidence of mirtazapine's effectiveness in treating akathisia.

pubmed

Резистентная к терапии шизофрения

Treatment-Resistant Schizophrenia
Strategies for Recognizing Schizophrenia and Treating to Remission

A Double-blind Randomized Controlled Trial of Olanzapine Plus Sertraline vs Olanzapine Plus Placebo for Psychotic Depression

Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy ({chi}21 = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001).

A Double-blind Randomized Controlled Trial of Olanzapine Plus Sertraline vs Olanzapine Plus Placebo for Psychotic Depression

Резистентные к лечению депрессии

Antidepressants can be grouped into 6 major categories: tricyclic antidepressants (TCAs), SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), serotonin neurotransmitter (5-HT2)-receptor antagonists (eg, nefazodone, trazodone), and novel agents (eg, mirtazapine, bupropion). If a patient fails to respond to one antidepressant class, it makes sense (at least conceptually) to switch to another, although most guidelines acknowledge that 2 failed trials of SSRIs may be justifiable before switching classes.
For example, in a study by Thase and colleagues,10 58 patients failed a trial of fluoxetine; however, there was a 76% response rate to citalopram among completers. Although this study was not blinded, it is interesting that citalopram (which is believed to be the most selective of the SSRIs) was effective when another SSRI was not.
Antidepressants that are associated with discontinuation symptoms (eg, paroxetine, venlafaxine, duloxetine) may produce discontinuation syndromes when stopped that can be erroneously attributed to adverse effects of the new drug, particularly if the new drug does not possess a significant degree of serotonin reuptake inhibition.
In a study by Zarate and colleagues,21 the onset of the antidepressant effect of ketamine occurred within 2 hours. Unfortunately, the drug must be given by intravenous infusion, but because the effect persisted for 7 days, ketamine treatment may be useful if given as a series.
Another NMDA-receptor antagonist now available in the United States is memantine (FDA-approved for Alzheimer disease). Memantine was shown to be effective in an open-label study in major depression. In a double-blind, randomized trial it showed comparable effects to escitalopram in patients with major depression and alcohol dependence.
Randomized controlled trials have supported the superior efficacy of a TCA/SSRI combination, as well as a mirtazapine/SSRI combination; open studies have done the same for TCA/MAOI and SSRI/bupropion combinations.
As with lithium, a recent review concluded that the trial data that support the efficacy of T3 augmentation are of better quality with TCAs than with SSRIs

Treatment-Resistant Depression

Резистентное к лечению биполярное расстройство

In acute mania, antidepressants should be discontinued immediately. The focus should be on using evidence-based treatments for mania. Although lithium is not recommended for mixed episodes or for patients with many previous episodes, lithium and divalproex are often used before an atypical antipsychotic because they are thought to be safer with long-term use.
The most commonly recommended nonstandard treatments for treatment-resistant mania are clozapine and ECT, which have been shown to have efficacy.A combination of clozapine and ECT has also been suggested.
Several novel treatments have been studied using an augmentation approach in combination with standard treatments for treatment-resistant mania. These include donepezil, gabapentin, topiramate, mexiletine, and intravenous magnesium sulphate. The reported efficacy in these uncontrolled reports is confounded by the continuation of the previous treatments. One exception is tamoxifen, which, like lithium and valproate, inhibits protein kinase C and was found to have antimanic efficacy superior to placebo.
However, antidepressants (other than fluoxetine in combination with olanzapine) have not been shown to be efficacious in acute bipolar depression and may be associated with switching. In particular, antidepressants with norepinephrine activity including tricyclics and serotonin-norepinephrine reuptake inhibitors may have a greater risk of inducing switching than SSRIs.
For treatment-resistant acute bipolar depression, the dopaminergic agonist pramipexole and the wakefulness-promoting agent modafinil have been shown to have efficacy greater than placebo as augmentation to standard treatments.4,26 Other pharmacotherapies have been studied in uncontrolled augmentation, including donepezil, bupropion, riluzole, gabapentin, levetiracetam, and aripiprazole. Two brain-stimulating therapies—magnetic seizure therapy and repetitive transcranial magnetic stimulation (TMS)—have been studied as well.
Other approaches include augmentation with hypermetabolic thyroid supplementation, diltiazem, aripiprazole, topiramate, gabapentin, mexiletine, levetiracetam, and chromium, as well as vagus nerve stimulation. Efficacy has also been reported for levetiracetam monotherapy and a combination of topiramate and clozapine.

Treatment-Resistant Bipolar Disorder

Воспалительная теория депрессии

Опять про теории депрессии.

Антидепрессанты и нейрогенез

Antidepressants and Neurogenesis in Humans

Синдром хронической усталости и депрессия

CFS has been linked to Epstein-Barr virus and human herpesvirus 6; however, study results have not been conclusive and the presence of these viruses does not always result in the development of CFS. Depression has been a common diagnosis, with as many as 80% of people affected with CFS misdiagnosed.
...
The majority of the scientific community now acknowledges that CFS does actually exist. While scientists have not yet identified the underlying cause of CFS or a definitive diagnostic test

Chronic Fatigue Syndrome – A Medical Mystery