Исследование антагониста орексинных рецепторов в терапии инсомнии

Study Objectives:

To assess the acute effects of SB-649868 in male subjects with Primary Insomnia with regard to (1) objective and subjective sleep parameters, (2) safety and tolerability, (3) next-day residual effects.

Design:

Multicenter, randomized, double-blind, placebo-controlled crossover study using a complete set of Williams orthogonal Latin Squares

Setting:

9 sleep centers in Germany

Patients:

52 male subjects with a diagnosis of primary insomnia (difficulty in sleep initiation and maintenance) confirmed by polysomnography

Interventions:

SB-649868 (10, 30, 60 mg) and placebo administered after dinner 90 minutes before bedtime

Measurements and Results:

Sleep effects assessed by polysomnography during 2 consecutive nights and by sleep questionnaires completed by subjects after each night at the sleep laboratory. Safety and tolerability were assessed by adverse events collection, electrocardiogram (ECG), vital signs, laboratory tests. Next-day residual effects were assessed by Digit Symbol Substitution Test, and modified Verbal Learning Memory Test administered at “lights on” after night 2. SB-649868 significantly reduced latency to persistent sleep, wake after sleep onset (WASO), and increased total sleep time (TST) compared to placebo. A dose-dependent effect was observed. A dose-dependent increase in absolute and percent REM sleep and reduction in REM sleep latency was observed mainly at the 60-mg dose. SB-649868 was well tolerated with inconsistent next day residual effects. SB-649868 sleep effects were correlated with SB-649868 circulating levels.

Conclusion:

The data demonstrate the sleep-promoting properties of the orexin antagonist SB-649868 in male patients with insomnia.

The Orexin Antagonist SB-649868 Promotes and Maintains Sleep in Men with Primary Insomnia 

Исследования арбаклофена

The investigational γ-aminobutyric acid type B (GABA-B) agonist STX209 (arbaclofen, Seaside Therapeutics) may improve social function and behavior in patients with fragile X syndrome (FXS).

In a randomized, controlled phase 2 study of children and adults with FXS, investigators from Rush University Medical Center in Chicago found that treatment with arbaclofen was well tolerated and improved social avoidance and problem behaviors.

Drug Shows Promise in Fragile X and Possibly Autism 

Гинго билоба не эффективен в профилактике болезни Альгеймера

Another large trial shows no benefit from ginkgo biloba extract in preventing Alzheimer disease, researchers report in the Lancet Neurology.

Nearly 2900 older adults without dementia who spontaneously reported memory complaints to their physicians were randomized to consume standardized ginkgo biloba extract or placebo for 5 years. Overall, the rate of diagnosis with probable Alzheimer's did not differ significantly between the ginkgo and placebo groups (1.2 and 1.4 cases per 100 person-years).

The authors note that a lower-than-expected Alzheimer's rate in both groups reduced the study's power, while a Lancet Neurology editorialist concludes: "For adults aged 70 years or older with a memory complaint who might be mildly cognitively impaired, use of [ginkgo biloba extract] does not decrease the risk of Alzheimer's disease over 5 years.

 Ginkgo Biloba: No-Go for Alzheimer's Prevention

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

Альтернативные методы коррекции СДВГ

Bacopa monnieri is an Ayurvedic medicinal herbal widely used as a tonic and memory enhancer. In a small 12-week double-blind RCT, 36 children with ADHD randomized to receive Bacopa, 50 mg BID, showed significant improvement over placebo in tests of sentence repetition, logical memory, and pair-associative learning.

A standardized extract of the bark from the French maritime pine (Pinus pinaster) may also help reduce symptoms of ADHD. A total of 61 children and adolescents randomized to a standardized extract of French maritime pine bark (Pycnogenol™), 1 mg/kg/d, for 1 month, experienced significant improvements in hyperactivity, inattention, and visual-motor coordination compared with placebo recipients; symptoms returned to pre-treatment baseline levels after a 1-month washout.

There is also promising evidence that zinc supplementation may mitigate ADHD symptoms. In a large 12-week double-blind placebo controlled trial (N = 400), children and adolescents randomized to a high dose of zinc, 150 mg/d, experienced significant improvement in hyperactivity and impulsivity but not inattention over placebo. In an augmentation study, the addition of zinc to methylphenidate resulted in greater improvement than methylphenidate alone.

 Alternative Medicine Therapies for ADHD

Изучение компульсивного поведения у собак

Researchers discovered a connection with stereotypic OCD behavior and vitamins and minerals. Dogs that received nutritional supplements, especially vitamins and minerals, with their food, chased their tails less.

“Our study does not prove an actual causal relationship between vitamins and lessened tail chasing, but interestingly similar preliminary results have been observed in human OCD,” said researcher Katriina Tiira, Ph.D.

 Study of Canine OCD May Help Humans

C-реактивный белок как предиктор резистентности к лечению депрессии, инфликсимаб в терапии резистентной депрессии

A new study suggests a drug used to treat autoimmune disorders and rheumatoid arthritis may help individuals with difficult-to-treat depression.

Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy.

The study investigated the use of infliximab, a new biologic drug used to treat autoimmune and inflammatory diseases. Each participant was assigned either to infliximab or to a non-active placebo treatment.

A biologic drug copies the effects of substances naturally made by the body’s immune system. In this case, the drug was an antibody that blocks tumor necrosis factor (TNF), a key molecule in inflammation that has been shown to be elevated in some depressed individuals.

Study participants all had major depression and were moderately resistant to conventional antidepressant treatment.

When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups.

However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab than to placebo.

Inflammation in this study was measured using a simple blood test that is readily available in most clinics and hospitals and measures C-reactive protein or CRP. The higher the CRP, the higher the inflammation, and the higher the likelihood of responding to the drug.

 Anti-Inflammatory Med May Ease Hard-to-Treat Depression

Стратегии потенцирования действия клозапина

Background. When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder.

Methods. Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g). Results. Twenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal.

Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies.

Conclusions. Evidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo.

 Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review

Противовирусные свойства флуоксетина

Surprisingly, fluoxetine stood out from the crowd. In a series of follow-up tests, the researchers found that fluoxetine interferes with the growth and replication of coxsackieviruses, a prominent subtype of enteroviruses.

The researchers repeated the experiment on several kinds of coxsackieviruses with recurring success. Without the ability to reproduce, these invading viruses simply would die off.

 Prozac May Have Antiviral Properties

Добавление креатина к СИОЗС

"There are some animal studies that show that this augmentation may be helpful, and there are older studies looking at enzymes in humans related to creatine that seem to be altered during episodes of depression, so there has been a sense that something may be going on here," he said.

"Creatine is a relatively harmless addition, so it's very testable, and would be very usable, and the fact that the American Journal of Psychiatry accepted the article signals genuine interest. It would be great to have a tool like this," he said.

 Dietary Supplement Speeds Clinical Efficacy of SSRIs

Генетические вариации эндоканнабиноидной системы и ответ на терапию циталопрамом

First line treatment of major depression is based on selective serotonin re-uptake inhibitors (SSRIs) that enhance serotonergic neurotransmission by blocking the serotonin transporter. However, clinical response is a complex phenomenon in which other systems such as the endocannabinoid system could be involved. Given the evidence for the role of the endocannabinoid system in the pathogenesis of depression as well as in the mediation of antidepressant drug effects, the aim of this study was to analyze genetic variability in the endocannabinoid system genes (CNR1, CNR2 and FAAH genes) and their role in clinical response (at week 4) and remission (at week 12) in SSRI (citalopram) treatment in a sample of 154 depressive outpatients, all of Spanish origin. All patients were treated with citalopram and followed over 12 weeks. Severity of depressive symptomatology was evaluated by means of the 21-item Hamilton Depression Rating Score (HDRS). No differences were found in any of the genotype distributions according to response or remission. The longitudinal study showed that (i) the CNR1 rs1049353-GG genotype conferred a better response to citalopram treatment in the subgroup of male patients and (ii) G allele carriers (CNR2 rs2501431) presented higher HDRS scores in the follow-up than AA homozygous allele carriers. Our results seem to suggest the involvement of CNR1 and CNR2 genes in clinical responses to citalopram treatment.

 Genetic variability in the endocannabinoid system and 12-week clinical response to citalopram treatment: the role of the CNR1, CNR2 and FAAH genes

Механизм резистентности к лечению шизофрении

Scientists have discovered a molecular mechanism for resistance to antipsychotic medications, a finding that may pave the way for the development of new drugs to treat a significant proportion of schizophrenia patients who do not respond to these medications.

Investigators led by Javier González-Maeso, PhD, assistant professor of psychiatry and neurology, Mount Sinai School of Medicine in New York City, found that long-term administration of atypical antipsychotic drugs selectively upregulates expression of the enzyme histone deacetylase 2 (HDAC2) in both mouse and human frontal cortex.

This epigenetic change, which is dependent on serotonin 5-hydroxytryptamine 2A (5-HT2A) upregulation, leads to lower expression of the metabotropic glutamate 2 receptor (mGlu2), thereby limiting the therapeutic effects of atypical antipsychotic therapy, often leading to a recurrence of psychotic symptoms.

According to investigators, blocking this cascade of events with HDAC inhibitors may improve responses to atypical antipsychotic drug therapy.

"Together, these data suggest that HDAC2 may be a new therapeutic target to augment the treatment of schizophrenia.... Specifically, our findings encourage the development and testing of HDAC2-selective inhibitors for schizophrenia," the investigators write.

 New Discovery Raises Hope for Drug-Resistant Schizophrenia

Исследования новых антипсихотиков: илоперидон, карипразин

Several trends dominated new research on antipsychotic medications presented at the 2012 American Psychiatric Association (APA) meeting and the 2012 New Clinical Drug Evaluation Unit (NCDEU) meeting sponsored by the American Society of Clinical Psychopharmacology. Data on the management of negative and cognitive symptoms of schizophrenia with antipsychotic depot injectables used either alone or with an adjunctive therapy are growing steadily, and a number of posters focused on that trend. In addition, long-term data were presented for several newer antipsychotics, both in schizophrenia and bipolar depression. Leslie Citrome, MD, MPH, commented on the data in an interview with Medscape shortly after the 2 meetings.

 Recent Research in Antipsychotics