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

Brain Dopamine–Serotonin Vesicular Transport Disease and Its Treatment

Known disorders of biogenic amine neuromediators (dopamine, norepinephrine, epinephrine, and serotonin) involve defects in nine enzymes1-9 and one transporter.10 Affected persons present in early childhood with symptoms referable to the affected neurotransmitter, and the disorders are diagnosed by measurement of neurotransmitter breakdown products in the cerebrospinal fluid (CSF). A deficiency in dopamine results in movement disorder; deficient norepinephrine or epinephrine causes autonomic dysfunction; and serotonin deficiency leads to sleep and psychiatric disturbances.2,3,6
We describe members of a family with symptoms of deficiencies in dopamine (dystonia, parkinsonism, and oculogyric crises), serotonin (sleep and mood disturbance), and epinephrine and norepinephrine (diaphoresis, temperature instability, ptosis, and postural hypotension), with no demonstrable deficiency of neurotransmitters in the CSF. Genome investigation revealed a mutation in the gene encoding VMAT2 that compromises transport of biogenic amines into synaptic vesicles, resulting in impairment of their synaptic transmission without detectable reductions in their amounts.

 Brain Dopamine–Serotonin Vesicular Transport Disease and Its Treatment

Возрастные изменения в фармакокинетике и факмакодинамике

Effects of Pharmacokinetic and Pharmacodynamic Changes in the Elderly

Анти-NMDA-рецепторный энцефалит и шизофрения

CONTEXT Evidence for symptomatic convergence of schizophrenia and N -methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders. OBJECTIVES To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis. DESIGN Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined. PARTICIPANTS Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n = 121), MD (n = 70), or BLPD (n = 38). MAIN OUTCOME MEASURES The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups. RESULTS Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R. CONCLUSIONS Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia and MD is different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia.

Increased Prevalence of Diverse N -Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia: Specific Relevance of IgG NR1a Antibodies for Distinction From N -Methyl-D-Aspartate Glutamate Receptor Encephalitis.

Эбселен как потенциальная замена литию

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself.

 A safe lithium mimetic for bipolar disorder.

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.

Полиморфизм CYP2D6 и приверженность лечению антидепрессантами

Early discontinuation of antidepressant drugs (ADPs) therapy is common, occurring in about 30% of patients by week 6.1, 2 Among the most relevant reasons for ADP discontinuation are adverse drug reactions and lack of improvement,3 which can be explained by interindividual variability in drug metabolism. Thus, discontinuation of amitriptyline or fluoxetine, two of the most commonly used ADPs worldwide, which are mainly metabolized by CYP2D6, could be related to CYP2D6 genetic polymorphism.

...

Despite the limitations of the present study (naturalistic observation, non-fixed dose, lack of evaluation of drug plasma concentrations and efficacy), a relationship between CYP2D6 polymorphism and early discontinuation of fluoxetine or amitriptyline monotherapy treatment was observed. There were differences across CYP2D6 groups in the rate of ADP discontinuation at week 4 (P < 0.01;Table 1). Overall, the rates of ADP discontinuation were 25, 36 and 46% at weeks 4, 8 and 12, respectively; no patient returned after dropout. All UMs discontinued treatment within the first 4 weeks, whereas no PM did so within 12 weeks.

 CYP2D6 ultrarapid metabolism and early dropout from fluoxetine or amitriptyline monotherapy treatment in major depressive patients

Экспериментальные антидепрессанты AZD6765 и GLYX-13

A small, randomized crossover study conducted by investigators at the National Institute of Mental Health Health (NIMH) showed that after a single infusion of AZD6765, almost 32% of the patients with treatment-resistant major depressive disorder (MDD) had a significant decrease in symptom scores 80 minutes later vs 15% of the patients after they had received matching placebo.

Although after receiving the experimental drug, the total decrease in scores lasted only for 30 minutes, some of the patients did experience residual antidepressant effects up to 2 days later.

 Experimental Drug May Help Depression 'in Minutes'

In clinical trials administered at 12 sites across the country, a single dose of GLYX-13 resulted in significant reductions in depression symptoms among subjects who had shown little improvement with previous drugs. (Subjects had failed treatment with one or more antidepressant agents.)

The positive effects of GLYX-13 were evident within 24 hours and lasted an average of seven days. Side effects of GLYX-13 were mild to moderate and were consistent with those observed in subjects receiving a placebo.

New Fast-Acting Antidepressant, GLYX-13, Shows Promise in Clinical Trials

Количество значительно взаимодействующих с фуранокумаринами лекарственных средств растёт

"The number of drugs on the market with the potential to produce serious adverse and in many cases life-threatening effects when combined with grapefruit has markedly increased over the past few years from 17 to 43 in four years," said lead researcher David Bailey, from the Lawson Health Research Institute in London, Ontario.

Citrus fruits such as limes and Seville oranges, often used in marmalade, also contain the active ingredients -- called furanocoumarins -- that cause the dangerous interactions, the researchers said. The chemicals apparently inhibit an enzyme that normally deactivates about half the effects of medication.

More New Drugs a Bad Fit With Grapefruit, Study Finds

Допаминовая система больных шизофренией резистентных к лечению

The authors conclude: 'Our findings suggest that there may be a different molecular mechanism leading to schizophrenia in patients who do not respond to anti-psychotic medication. Identifying the precise molecular pathway particularly in these patients is of utmost importance and will help inform the development of much-needed novel treatments.'
Researchers used PET scan imaging to investigate dopamine synthesis capacity in 12 patients with schizophrenia who did not respond to treatment, 12 who did, and 12 healthy controls. They found that schizophrenia patients whose illness was resistant to antipsychotic treatment have relatively normal levels of dopamine synthesis capacity which would explain why the dopamine blocking anti-psychotic medication was not effective in this group.

 Research may explain why some people with schizophrenia do not respond to treatment

Психофармакологические тесты в диагностике аффективных расстройств

Таким образом, для выбора адекватной терапии приступов аффективных психозов необходимо понять структуру состояния больного, отражающую механизмы образования его синдрома. Для этой цели клинический метод успешно дополняется психофармакологическими тестами. Лечение аффективных и аффектив­но-бредовых больных (кроме маниакальных) целесообразно начи­нать с пробного терапевтического курса анксиолитиками (феназепамом, лепонексом) или с диазепамового теста. В зависимости от трансформации клинической картины, указывающей на основ­ное биологическое расстройство, на «блок», являющийся основой патологического состояния, в дальнейшем назначаются антиде­прессивные или энергизирующие препараты. Создается впечатление,  что сфера применения нейролептиков в терапии аффективных приступов должна быть весьма ограниченной рамками маниакаль­ных и маниакально-параноидных состояний, в комбинации с нормотимиками.

 Точилов В.А. - ОБ ИССЛЕДОВАНИИ СТРУКТУРЫ И ЛЕЧЕНИИ АФФЕКТИВНЫХ ПРИСТУПОВ

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

Связь вируса простого герпеса первого типа со снижением когнитивных функций у больных шизофренией

Latent infection with neurotropic herpes viruses, such as herpes simplex virus, type 1 (HSV1), has been generally considered benign in most immunocompetent individuals except for rare cases of encephalitis. However, several recent studies have shown impaired cognitive functions among individuals with schizophrenia exposed to HSV1 compared with schizophrenia patients not exposed to HSV1. Such impairments are robust and are prominently observed in working memory, verbal memory, and executive functions. Brain regions that play a key role in the regulation of these domains have shown smaller volumes, along with correlation between these morphometric changes and cognitive impairments in schizophrenia. One study noted temporal decline in executive function and gray matter loss among HSV1-exposed first-episode antipsychotic-naïve schizophrenia patients. Furthermore, a proof-of-concept double-blind placebo-controlled trial indicated improvement in cognitive performance following supplemental anti-herpes–specific medication among HSV1 seropositive schizophrenia patients. Cross-sectional studies have also identified an association between HSV1 exposure and lesser degrees of cognitive impairment among healthy control individuals and patients with bipolar disorder. These studies fulfill several Bradford-Hill criteria, suggesting etiological links between HSV1 exposure and cognitive impairment. Exposure to other human herpes viruses such as cytomegalovirus and herpes simplex virus type 2 (HSV2) may also be associated with cognitive impairment, but the data are less consistent. These studies are reviewed critically and further lines of enquiry recommended. The results are important from a public health perspective, as HSV1 exposure is highly prevalent in many populations.

 Exposure to Herpes Simplex Virus Type 1 and Cognitive Impairments in Individuals With Schizophrenia

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