Отсутствие эффективности в РКИ: зипрасидон при биполярной депрессии и ламотриджин при депрессии

Both bipolar depression and refractory unipolar depression are highly difficult to treat. Because few randomized controlled trials (RCTs) address these conditions, clinicians often try medications either from the same class as proven-effective agents or that are effective for related conditions. These two large, well-conducted RCTs remind us that such clinical strategies may be neither sound nor effective.

What Lamotrigine and Ziprasidone Are Not Good For 

Предиктор эффективности терапии эсциталопрамом

A recent Loyola study found that the blood test for a protein called vascular endothelial growth factor (VEGF) could help predict successful treatment. The researchers found that among depressed patients who had higher than normal levels of VEGF, more than 85 percent experienced partial or complete relief after taking escitalopram (Lexapro).

 Blood Test May Predict Antidepressant Effectiveness

Ранняя диагностика шизофрении

The study of the preventive potential of pre-onset or psychosis-risk intervention requires a common and reliable diagnosis of a risk syndrome with which to construct samples that we can track and treat and that can be replicated by independent clinical investigators. Yung and McGorry10 created the Comprehensive Assessment of At-Risk Mental States (CAARMS), a structured interview for diagnosing the psychosis-risk syndrome. Our team at Yale developed the Structured Interview for Psychosis-Risk Syndromes (SIPS); this tool is used to rate the severity/frequency of key prodromal symptoms and can be used to determine the presence or absence of several psychosis-risk syndromes. It can also be used to estimate the severity of these symptoms and syndromes, including the boundary of transition from the prodrome to psychosis, called “conversion.”
The interrater reliability of the SIPS is satisfactory. Moreover, the SIPS has proved to be a valid predictor of psychosis insofar as psychosis developed over the next 2.5 years in approximately 33% of a large sample of treatment-seeking persons meeting SIPS criteria. In essence, approximately 1 of 3 persons who met an SIPS prodromal diagnosis became psychotic, which amounts to a risk for psychosis that is more than 400 times the risk for the average individual. Some of the remaining two-thirds of the sample who met an SIPS prodromal diagnosis and in whom psychosis did not develop remained prodromally symptomatic and eventually met criteria for schizotypal personality disorder; in others, Axis I disorders, such as depression, developed; and in many, prodromal symptoms remitted with time without sequelae (J. Addington et al, unpublished data, 2010).

Treatment research in psychosis risk has just begun, and initial findings show promise. Combined antipsychotic (risperidone) and individual psychotherapy, antipsychotic therapy alone (olanzapine), and psychotherapy (cognitive-behavioral therapy) alone all show that onset of psychosis in prodromal samples can be delayed, but often with substantial adverse effects (eg, weight gain with olanzapine). Most recently, a randomized trial of v-3 fatty acids delayed onset of psychosis with virtually no adverse effects. In this study, the risk to benefit ratio is remarkably good, and if the results can be replicated, they should essentially eliminate concerns about untoward adverse effects in false-positive cases. Overall, however, many more treatment studies are needed before integrated guidelines can be formulated.

Early Antecedents and Detection of Schizophrenia

Оланзапин при резистентной мании

Objective

To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania.
Method

Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5–40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate.
Results

The mean change in YMRS total score from baseline to endpoint was −23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia.

Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study

РКИ варениклина при шизофрении

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4β2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2–8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline–placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Adjunctive Varenicline Treatment with Antipsychotic Medications for Cognitive Impairments in People with Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial

Галлюцинации

Hallucinations: Common features and causes

Ухудшение депрессивной симптоматики у группы больных в исследовании дулоксетина

New research shows that while many antidepressants help most people who take them, a small group of people who take them will actually feel more depressed than if they had just been taking a placebo or sugar pill.

 Some People Feel Worse on Antidepressants Like Cymbalta

Do Antidepressants Make Some People Worse?

Взаимодействие рецепторов серотонина и глутамата как возможный механизм психоза

Serotonin (5HT) and glutamate are two neurotransmitters. Up until now, it was thought that they acted independently. A given neuron might have receptors for both serotonin and glutamate, but they didn't interact: serotonin would never affect the glutamate receptors, and vice versa.
The new research overturns that view. Authors Miguel Fribourg and colleagues ofMount Sinai School of Medicine show, in a series of elegant experiments in mice, that different receptors can cluster together, forming a complex. The two receptors, serotonin's 5HT2A and glutamate's mGluR2, can talk to each other.

A Psychedelic Tale of Two Neurotransmitters

Артериальная гипертензия, липопротеины низкой плотности и депрессия

Abstract
Background
Clinicians generally agree on the association between depression and hypertension. Less clear is if the nature of the link is direct or indirect and if this should be considered confined only to syndromal forms or if it concerns also subsyndromal affective presentations. This study investigated the nature of the association between hypertension and subsyndromal depression in hospitalized hypertensive patients.
Methods
196 hypertensive and 96 non hypertensive inpatients underwent a SCID interview, to exclude patients positive for any Axis I or Axis II diagnosis. Symptomatic Subsyndromal Depression (SSD) was identified according to criteria proposed by Judd. Psychopathological assessment was performed with Anxiety Sensitivity Index (ASI) and Hopkins Symptom Checklist-90 (SCL-90). Clinical assessments included blood pressure measurement, evaluation of general health conditions and screening cardiovascular risk factors (smoke, alcohol, body weight, sedentary life style).
Results
Hypertensives met more frequently criteria for SSD. They also scored higher on ASI and SCL-90. However, those with more severe physical conditions, if compared with more healthy patients, did not show increased psychopathological severity. Similarly, psychopathological symptom severity did not differ among hypertensives positive for other cardiovascular risk factors, commonly more frequent among depressed subjects.
Limitations
Further analyses are needed to explore the potential advantage obtained on blood pressure control by treating SSD.
Conclusions
Hospitalized hypertensives, more frequently satisfied criteria for Symptomatic Subsyndromal Depression. These milder affective forms are probably directly linked to the presence of hypertension, rather than being indirectly associated to physical impairment or to higher prevalence of other cardiovascular risk factors.

Symptomatic subsyndromal depression in hospitalized hypertensive patients

Objective
Serum cholesterol was reported to be associated with depressed mood, but the studies conducted among household population are rare.
Methods
We used the data of 4115 men and 4275 women aged 18 or older, who completed a depression screening interview and had blood collected as a part of the National Health and Nutrition Examination Survey, 2005–2008. The serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were gender-specifically categorized into lower, intermediate, and upper quartiles. Depression was measured using the Patient Health Questionnaire, a 9-item screening instrument asking about the frequency of depression symptoms over the past 2weeks.
Results
After adjustment for socio-demographics and behavioral risks, a U-shaped association was detected between severe depression and LDL-C among men. The odds ratios (ORs) of severe depression were 5.13 (95% CI=1.74–15.09), 1 (reference) and 2.28 (1.07–4.86) respectively for the men with lower (<169mg/dL), intermediate (169–221mg/dL), and upper quartile (≥222mg/dL) LDL-C. Among women, lower HDL-C was significantly associated with an elevated odds of severe depression [OR=2.96 (1.59–5.52)] compared with upper quartile of HDL-C, the association diminished after adjustment for covariates [OR=1.24 (0.66–2.32)]. No clear pattern of association between cholesterol and moderate depression was observed from either men or women.
Limitation
The inherent limitation of cross-sectional design prevented the authors from investigating causality.
Conclusions
A U-shaped association was identified between LDL-C and severe depression among men. Further studies are necessary to explore the biological mechanism and identify the clinical implication among populations vulnerable to psychiatric disorders.

Low cholesterol is associated with depression among US household population 

Антидепрессивный эффект МРТ

Yes, this study says that having an MRI scan has a powerful antidepressant effect.
They took 51 depressed patients, and gave them all either an MRI scan or a placebo sham scan. The sham was a "scan" in a decommissioned scanner. The magnet was off but they played recorded scannerish sounds to make it believable. Patients were blinded to group.
They found that people in the scanner group improved much more than those in the sham group over two weeks. Actually there were two different kinds of scans, T1 structural MRI and EPI functional MRI, but they were the same

 Does MRI Make You Happy?

Ещё одно неудачное исследование антидепрессанта нового механизма действия

On 8 November, Targacept, a drug company based in Winston-Salem, North Carolina, announced that TC-5214 had performed no better than placebo in one of four phase III trials. The results are a disappointment to clinicians eager for an innovative antidepressant.

TC-5214 is a form of mecamylamine, a blood-pressure drug introduced in the 1950s. It targets nicotinic α4β2 receptors (see ‘Mixed signals’), which normally receive chemical signals from the neurotransmitter acetylcholine. Because excess acetylcholine has been linked to major depression, blocking these signals might relieve the condition.

 Depression drug disappoints

Сравнительный анализ атомоксетина и метилфенидата при СДВГ

Background
Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications.
Methods
All published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IVTM criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD) was used as a measure of effect size.
Results
Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD= 0.09, 95% CI -0.08-0.26) (Z=1.06, p=0.29). Synthesis of data from eight trials found no significant difference in response rates (RR=0.93 95% CI 0.76-1.14, p=0.49). Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD=0.32, 95% CI 0.12-0.53 (Z=3.05, p<0.002). Immediate release methylphenidate was not superior to atomoxetine (SMD= -0.04, 95% CI -0.19-0.12) (Z=0.46, p=0.64). Excluding open label trials did not significantly alter the effect size (SMD=0.08, 95% CI -0.04-0.21) (Z=1.27, p=0.20). All-cause discontinuation was used as a measure of acceptability. There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71). There was significant heterogeneity among the studies (p=0.002, I2=67%). Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p=0.001, I2=81%).
Conclusions
In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents.

Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis

Результаты исследования антидепрессанта тройного действия

A paper just out reveals that the snappily-named GSK372475 doesn't work and has lots of side effects. It's a report of two clinicals trials in which Glaxo's contender was pitched against placebo and against older antidepressants in the treatment of depression.

Another Antidepressant Bites The Dust

Антидепрессивная активность клавулановой кислоты не подтвердилась

The randomized, double-blind, placebo-controlled study compared two doses of Serdaxin, 0.5 mg and 5 mg, to placebo over an 8-week treatment period. Results from the study did not demonstrate Serdaxin's efficacy compared to placebo measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

Rexahn Pharmaceuticals Announces Phase II Results for Serdaxin as Treatment for Major Depressive Disorder

ИАХЭ и холинолитики взаимно снижают эффективность друг друга

Many patients with Alzheimer's disease are simultaneously prescribed cholinesterase inhibitors (ChIs) and anticholinergics (AChs), 2 drug classes that have the potential to cancel each other out.

Meds Prescribed for Alzheimer's May Cancel Each Other Out