Глутаматергические механизмы ОКР

Glutamatergic Dysfunction in Obsessive-Compulsive Disorder and the Potential Clinical Utility of Glutamate-Modulating Agents

Альтернативные методы лечения шизофрении

Outside of India, however, Sen and Bose's observations on the use of rauwolfia for psychotic disorders were generally ignored. It was not until 1954, when Nathan Kline2 reported that both whole root rauwolfia extract and reserpine—a purer preparation—seemed to be somewhat more effective than placebo in more than 400 inpatients with neuropsychiatric conditions, that clinicians in the West took notice. Although it soon became apparent that phenothiazines were generally more tolerable than reserpine, and even after our enthusiastic embrace of clozapine, a respected 1991 review3 still listed reserpine as 1 of 8 reasonable, evidence-based treatment options for persons affected with the refractory symptoms of schizophrenia.

Two essential omega-3 fatty acids were compared in a 3-month, double-blind pilot study that found that augmentation with eicosapentaenoic acid (EPA) was superior to docosahexaenoic acid (DHA) or placebo in significantly reducing Positive and Negative Syndrome Scale (PANSS) scores; a second study using EPA suggested that supplementation with omega-3 for extended periods can benefit some patients even without antipsychotics.

On the other hand, a 16-week trial in 87 patients that compared 3 g/d of e-EPA with placebo found no difference in positive, negative, mood, or cognitive symptoms of schizophrenia.26 Noting that both the active and placebo groups had improvements in their PANSS ratings, these investigators evaluated the placebo response in 37 study participants and found that the 9.5% improvement in the PANSS total score usually occurred by the end of the first 2 weeks of participation, which argues for the value of a placebo run-in phase for future studies.27

Revisiting the initial findings of plasma membrane abnormalities, a 24-hour dietary recall in 146 community-dwelling patients with schizophrenia found little difference in dietary fatty acid and antioxidant intake from controls.28 However, a more elaborate evaluation of 72 subjects with schizophrenia found that the previously reported membrane lipid abnormalities could be explained by the fact that many of the subjects were smokers and had a significantly different omega-3 dietary intake from that of the controls.

Sitting between mainstream and alternative therapies are amino acid treatments, derived from the recognition that phencyclidine (PCP) psychosis was a better model for schizophrenia than the previous model of amphetamine psychosis. Among other observations, those with PCP intoxication presented with negative as well as positive symptoms. The mechanism of PCP's action was eventually elucidated; it specifically blocked the ion channel in NMDA (N-methyl-d-aspartate) glutamate receptors in the brain. An allosteric modulatory site on this complex receptor has been referred to as the "glycine" site, and its endogenous ligands plausibly may be the amino acids glycine, d-serine, and d-alanine (the latter 2 unusual d-forms present in the brain because of a racemizing enzyme).

A meta-analysis of short-term clinical trials found that treatment augmented with the agonists glycine and d-serine moderately reduced negative symptoms, while partial agonist d-cycloserine was less efficacious.35 These agents do not appear helpful for patients treated with clozapine, although glycine and d-serine may be effective for those being treated with olanzapine or risperidone.

High homocysteine levels have been found to interfere with NMDA receptors in animal studies. Neeman and coauthors46 reported finding lower plasma glycine levels and higher homocysteine levels in patients with schizophrenia compared with controls, and glycine levels correlated with increased negative symptoms. Findings of higher homocysteine levels in patients with schizophrenia may often involve folate-deficient dietary choices, obesity, or cigarette smoking, but one study found that these variables explained relatively little of the high homocysteine levels

Oxidative stress/free radical damage has been proposed as mediating pathology in various neuropsychiatric disorders, including schizophrenia. Small initial trials failed to shed adequate light on the value of ascorbic acid (vitamin C) in the treatment of schizophrenia,49,50 although a recent 8-week study reported significant improvement in Brief Psychiatric Rating Scale scores for those receiving an adjunctive 500 mg/d dosage of vitamin C.51 In addition, one study25 with positive findings used adjunctive omega-3 with vitamins C and E. Additional studies are needed to evaluate this approach.

Another putative adjunctive antioxidant strategy in schizophrenia involves the addition of EGb, a standardized Ginkgo biloba extract. Although several studies have shown fairly consistent preliminary results,52-54 larger and more definitive studies are still needed.

The higher rates of schizophrenia in those born in winter or spring, and the reported association between prenatal exposure to the 1945 famine of the "Dutch Hunger Winter" and later development of schizophrenia in offspring may be rationalized by the hypothesis that schizophrenia is more prevalent in those who have had vitamin D deficiency during the first year of life. The results of a 1966 study of a Finnish-birth cohort lend support to this theory.63 However, as there were very few children not given the then-recommended vitamin D supplement, and since not receiving the supplement may have been associated with other plausible risk factors, this single study provides only weak support for this interesting idea.

Treatment Resistance in Schizophrenia: The Role of Alternative Therapies

Каннабиноиды и аппетит

In addition, research published in the Proceedings of the National Academy of Sciences, and blogged about by Neuroskeptic, showed that CB1 cannabinoid receptors on the tongue selectively boost our pleasurable responses to sweet-tasting food. Conversely, drugs that block cannabinoid receptors have been actively pursued as appetite suppressants. One such drug, trade name rimonabant, was disallowed by the FDA on the grounds that it worked so well in the guise of anandamide’s opposite number that it frequently caused debilitating depression in users. But it did appear to reduce appetites.

Addiction Inbox

налтрексон

While naltrexone has yet to become the huge treatment breakthrough for alcoholism that addiction researchers hoped for it, naltrexone did, in the end, prove to be the first anti-craving medication widely available for alcoholics. Using an opiate antagonist as an aid to the prevention of alcoholic relapse would have been unthinkable without the underpinnings of a neurophysiological model of addiction. Various investigators have also speculated that naltrexone, the drug used as an adjunct of heroin withdrawal therapy, may find use against symptoms of marijuana withdrawal in people prone to marijuana dependence

Naltrexone has something of a mixed reputation, however, in part due to its use in the highly controversial practice of “rapid detox.” Naltrexone, like methadone and buprenorphine, blocks the heroin high in a relatively neutral manner. It does so by knocking the opiate molecule off its receptors and replacing it with “dead weight,” so to speak. Naltrexone would seem to be the perfect drug for heroin addicts—but it is not. It does little to reduce cravings. Like acamprosate for alcohol, another blocking approach, its record of accomplishment is mixed, and the dropout rate is high. There is not even a mild drug-like effect to provide cross-tolerance and dampen the effects of withdrawal, as with methadone. Recently, naltrexone for heroin addiction has been offered as a form of rapid detoxification.

Naltrexone combined with buprenorphine is marketed as Subutex, and represents another treatment modality for opiate addiction. In addition, a University of Minnesota study of kleptomania—the compulsion to steal—showed that naltrexone drastically reduced stealing among a group of 25 shoplifters.

Unfortunately, naltrexone is a potential problem for people with liver disease or hepatitis. At high doses, naltrexone has been implicated in liver damage. More common adverse effects include dizziness, lethargy, and headache.

Addiction Inbox

Антипсихотики второго поколения в сравнении с перфеназином в терапии депрессивного синдрома у больных шизофренией

Second-generation antipsychotics (SGAs), also known as aytypicals, are not superior to the first-generation antipsychotic perphenazine in treating depression in patients with chronic schizophrenia

Although a significant improvement in depressive symptoms was found in all treatment groups over time, subanalyses found that quetiapine was significantly more effective than risperidone in the patients having a major depressive episode (MDE)

No Evidence to Support Recommendation to Use Atypicals Over First-Generation Antipsychotic

закрывают больницы

закрывают больницы
Собираются закрывать Городской психоневрологический диспансер №7. Отбирают здания на Троицком, на Канонерской улице. Следующая на очереди - больница на Пряжке. Врачи, мед. персонал и родственники пациентов пытаются отстоять клиники. Под катом - письмо Президенту РФ, сегодня собрали подписи и отправили в администрацию. Для интересующихся развитием событий и неравнодушных ссылка на сообщество

http://www.democrator.ru/problem/3200
http://community.livejournal.com/ru_psychiatry/606925.html

Магнитносудорожная терапия vs ЭСТ

Enter magnetic seizure therapy (MST). As the name suggests, this is like ECT, except it uses powerful magnets, instead of electrical current, to cause the seizures. In fact though, the magnets work by creating electrical currents in the brain by electromagnetic induction, so it's not entirely different.

MST is thought to be more selective than ECT, in that it induces seizures in the surface of the brain - the cerebral cortex - but not the hippocampus, and other structures buried deeper in the brain, which are involved in memory.

After 12 sessions, MST and ECT both seemed to work, and they were equally effective on average. Some patients got much better, some only got a bit better.

What about side effects? MST was noticeably "gentler", in that it didn't cause headaches or muscle pain, and people recovered from the seizures much faster (2 minutes vs 8 minutes to reorientation) after MST. This may have been because the seizures (as assessed using EEG) were less intense.

In terms of the all-important memory and cognitive side effects, however, it's not clear what was going on. They used a whole bunch of neuropsychological tests. In some of them, people got worse over the course of the sessions. In others, they got better. But in several, the scores went up and down with no meaningful pattern. If anything the MST group seemed to do a bit better but to be honest it's impossible to tell because there's so much data and it's so messy.

Shock and Cure - With Magnets

Неотложные состояния при аффективных расстройствах

Pharmacological treatments for bipolar disorder can cause or compound patients' behavioral disturbances. Treatment with antipsychotics can increase the risk of agitation or aggression by causing akathisia, which can be associated with severe exacerbation of symptoms or even suicide attempts. The risk of akathisia is reduced but not eliminated by the use of atypical antipsychotics. Antidepressant agents can cause activation or mood destabilization, and some of these agents have been reported to cause akathisia.

Principles of treatment

A treatment strategy for impulsivity or aggression requires knowledge about possible interacting causes of the behavioral disturbance, its course, and its context. This information is helpful in formulating initial treatment and is even more helpful in developing a long-term strategy that will, if successful, reduce the patient's need for future emergency care.

Factors that influence treatment of pathological impulsivity and aggression include:

* Degree of premeditation versus degree of impulsiveness.
* Role of nonpsychiatric conditions (drug toxicity, drug withdrawal, delirium, dementia, infection, metabolic abnormality).
* Relationship to a DSM-IV Axis I psychiatric disorder.
* Relationship to a personality disorder.
* Course (acute/fluctuating versus chronic).
* Presence of prominent overstimulation.
* Environmental context (legal, relationship, and/or economic problems or changes).
* Personal context (personality characteristics, conflicts).

Candidate mechanisms of treatment for impulsive aggression or agitation include:

* Enhancing an inhibitory system, such as serotonin or GABA.
* Inhibiting an activating system, such as dopamine.
* Stabilizing fluctuations in inhibitory and/or excitatory systems.
* Protecting against overstimulation or normalizing arousal.

Psychiatric Emergencies in Bipolar and Related Disorders

Эффективность омеги-3 в предупреждении послеродовой депрессии

For this study, 2399 pregnant women at less than 21 weeks' gestation were enrolled between October 2005 and January 2008 at 1 of 5 Australian maternity hospitals. The women were then randomly assigned to receive either 800 mg daily of DHA-rich fish oil capsules (n = 1197) or matching vegetable oil capsules without DHA (placebo/control group, n = 1202) at baseline, continuing until they gave birth.

The mean age for both groups was 29.9 years, and the median gestational age at trial entry for both groups was 19.0 weeks.

Assessments for adverse gastrointestinal or bleeding events were conducted by telephone at 22, 28, and 36 weeks' gestation.

At 6 weeks and at 6 months postpartum, the mothers were assessed for depressive symptoms using the self-administered Edinburgh Postnatal Depression Scale. The study's primary maternal outcome was a high level of depressive symptoms, which was defined as "a score of more than 12."

Follow-ups were conducted with 694 of the children at the age of 18 months (DHA group, n = 333; placebo group, n = 361). The investigators used the Bayley Scales of Infant and Toddler Development, Third Edition, to evaluate both cognitive and language development.

Neurodevelopment was the study's primary childhood outcome. Secondary outcome measures included an evaluation scale of gross and fine motor functioning and parental report scales of social–emotional behavior and adaptive behavior.

Little to No Effect

Results showed that 96.7% of the enrolled women completed the study.

During the first 6 months postpartum, high levels of depressive symptoms in those taking the DHA capsules (9.67%) and those taking the placebo (11.19%) did not differ significantly (adjusted relative risk [RR], 0.85; 95% confidence interval [CI], 0.70 - 1.02; P = .09).

"Interestingly, our data did suggest a 3% to 4% reduction in depressive symptoms in the subgroup of women who had a previous history of depression," said Dr. Makrides. "It may be that these women [would] benefit from supplementation, but other studies are needed to confirm this."

However, "the percentage of women with a new medical diagnosis for depression during the trial or a diagnosis requiring treatment did not differ between groups," write the study authors.

There were also no significant differences in mean cognitive composite scores for the children of mothers in the DHA group vs those in the control group (adjusted mean difference, 0.01; 95% CI, −1.36 to 1.37; P = .99).

However, fewer infants in the DHA group had scores indicating delayed cognitive development than did those in the control group (2.71% vs 6.64%; P = .007).

Although there were no overall between-group differences in mean language composite scores (adjusted mean difference, −1.42; 95% CI, −3.07 to 0.22; P = .09), or between boys in both treatment groups, the girls in the DHA group had a lower mean language score (P < .001) and an increased risk for delayed language development (P = .03) than did the girls in the control group.

No overall between-group differences were found for motor development, social–emotional behavior, and adaptive behavior. However, the girls in the DHA group had poorer mean adaptive behavior scores than did those in the control group (P = .003).

The DHA-treated group had fewer preterm births of less than 34 weeks' gestation (1.09%) compared with those treated with placebo (2.25%; adjusted RR, 0.49; P = .03), but the DHA group had "more postterm births requiring obstetric intervention," including inductions or cesarean deliveries (17.59% vs 13.72%; adjusted RR, 1.28; P = .01).

"Clearly these trade-offs are important to consider, and it may be that DHA supplementation may be most useful to women at risk of having a preterm baby," noted Dr. Makrides.

Finally, at least 1 serious adverse event was reported for 36 of the DHA-group infants vs 54% of those in the control group (RR, 0.67; P = .06). Eructations were reported by more women in the DHA group than in the control group at both 28 weeks' (43.6% vs 25.6%) and 36 weeks' (41.5% vs 29.2%) gestation (P < .001 for both time points).

"This is the largest and most well-conducted study of its type, [and] we have a conclusive result about the fact that there is little or no effect of DHA supplementation during normal pregnancy on postpartum depression or early childhood neurodevelopment in the first 18 months of life," summarized Dr. Makrides.

No Benefit of DHA Fish Oil for Postpartum Depression, Child Neurodevelopment

механизм работы СИОЗС

In a recent publication in Science, a team of researchers showed a possible mechanism of action for Fluoxetine. According to these scientists, it works through a completely new inhibitory pathway, which can also explain the lengthy and for patients often very frustrating waiting time before SSRIs work clinically. They found that in mice chronically fed with Fluoxetine, the expression of the gene that encodes the blueprint of SERT is reduced, which means less SERT is available to remove serotonin from the synapse. This is a surprising finding in itself, still, the mechanism how Fluoxetine down-regulates the SERT expression is even more surprising.

How Prozac works

Депрессия и тревожные расстройства в пожилом возрасте

Anxiety and Depression in the Elderly

Психотропные средства при заболеваниях почек

Update on Psychotropic Medication Use in Renal Disease

Normally, after eating, your body uses carbohydrate as the main energy source. After a long time hungry, it switches to fat. Zyprexa made the body use fat all the time

SUMMARY: A class effect, to varying degrees; and eating less may not help.


1. Food intake was the same between controls and Zyprexaers. You get these effects even if you eat the same.

2. This effect is shared by other atypicals, in a predictable fashion:


In the fed state, Zyprexa and Clozaril do a massive conversion to fat utilization, Risperdal a medium, and sulpiride minimal covnersion.

In the fasting state:

Geodon has a lesser effect than Zyprexa, and appears to normalize; Abilify and Haldol seem close to normal.

3. These effects are consistent with Lilly's own studies that the majority of weight gain happens in the first month, and not suddenly after a year of use.

4. There is still a hunger component to weight gain that is separate from the metabolic effect. Some drugs will make you hungry, change your metabolism, or some mixture of the two. Hunger appears to be a H1 mediated process (Seroquel, Zyprexa, Clozaril, Remeron, Paxil>Prozac, etc.)

5. The immediate clinical consequence of this information is probably (paradoxically) to tell the patients to eat less sugar.

Unless you dramatically cut fat out of your diet, the body will still churn through what fat you do eat at the expense of carbohydrate. Better, and easier, to reduce the carb load that lingers in your body (and likely ultimately gets stored.)

Why Zyprexa (And Other Atypical Antipsychotics) Make You Fat

PHQ-9

Table 3. PHQ-9

1. Over the past 2 weeks, how often have you been bothered by any of the following problems?
	Not at all (0)	Several days (1)	More than half the days (2)	Nearly every day (3)
a. Little interest or pleasure in doing things
b. Feeling down, depressed, or hopeless
c. Trouble falling/staying asleep, sleeping too much
d. Feeling tired or having little energy
e. Poor appetite or overeating
f. Feeling bad about yourself -- or that you are a failure or have let yourself or your family down
g. Trouble concentrating on things, such as reading the newspaper or watching television
h. Moving or speaking so slowly that other people could have noticed. Or the opposite -- being so fidgety or restless that you have been moving around a lot more than usual
i. Thoughts that you would be better off dead or of hurting yourself in some way
2. If you checked off any problem on this questionnaire so far, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?
	Not difficult at all	Somewhat difficult	Very difficult	Extremely difficult

Table 4. Interpretation of PHQ-9 Results

Score/ Symptom Level	Treatment
0-4 No depression	Consider other diagnoses
5-9 Minimal	▪ Consider other diagnoses ▪ If diagnosis is depression, watchful waiting is appropriate initial management
10-14 Mild	▪ Consider watchful waiting ▪ If active treatment is needed, medication or psychotherapy is equally effective; consider function score in choosing treatment
15-19 Moderate	▪ Active treatment with medication or psychotherapy is recommended ▪ Medication or psychotherapy is equally effective
20-27 Severe	▪ Medication treatment is recommended ▪For many people, psychotherapy is useful as an additional treatment ▪ People with severe symptoms often benefit from consultation with a psychiatrist

Data from Kroenke K, Spitzer R. Psychiatr Ann. 2002;32:509-521.

A number of combinations have some benefit in selected patients, including:

• Lithium augmentation at stage 3 of STAR*D resulted in remissions in 15.9%.^[84] Lithium in combination with SSRIs and TCAs also has been effective in placebo-controlled studies, most involving small numbers of subjects. Such treatment requires monitoring of lithium levels, because there is a small difference between therapeutic and toxic levels.^[85]
• Thyroid hormone, and particularly triiodothyronine, has been studied for augmentation with the TCAs. In the STAR*D study, at step 3, augmentation with triiodothyronine led to a remission rate of 24.7%.^[84] Placebo-controlled studies have involved small numbers of subjects and have had mixed results.^[86]
• A heterocyclic-SSRI combination in 1 small study produced more rapid treatment onset and increased the likelihood of remission.^[87] In the study, a combination of fluoxetine and desipramine (a norepinephrine reuptake inhibitor) was more effective in achieving remission than either drug used as monotherapy: 53.8% for the combination, compared with 7.1% and 0%, respectively. However, such combinations can produce the serotonin syndrome, which is potentially life-threatening, and the dose of the heterocyclic must be adjusted using blood levels because SSRIs increase TCA levels through CYP-450 isoenzyme interactions (eg, fluoxetine increases the levels of desipramine 3- to 4-fold).^[88] Consequently, this augmentation strategy should rarely be considered in primary care.
• Mirtazapine has recently been evaluated in combination therapy with an SSRI (fluoxetine), an SNRI (venlafaxine), or bupropion.^[89] The investigators found that all 3 combinations were more effective than fluoxetine alone in achieving remission (52%, 58%, 46%, respectively, compared with 25%). In patients who responded, double-blind discontinuation resulted in relapse in about 40%. Of note, treatment was initiated with these combinations, rather than mirtazapine being used as an augmenting agent in those not initially responding.
• Methylfolate and folate have been used to augment SSRIs, resulting in increased rates of remission, particularly in women.^[90] The degree to which the response is due to folate deficiency, and whether methylfolate is of greater benefit due to its increased ability to cross the blood-brain barrier, are subject to further research.
• Antidepressants and hypnotics have been used together, with early improvement not only in sleep measures, but also in rates of depression remission.^[91]
• Stimulant drugs have been used as augmentation of heterocyclics or SSRIs.^[92] Of note, in individuals with comorbid medical illness, amphetamine stimulants should be used with caution, particularly if cardiac disease is potentially present.

Clinical and Pharmacologic Strategies to Achieve Remission in Depression

Карипразин

Forest Laboratories Inc. and Gedeon Richter announced in September the preliminary results from an eight-week phase 2 clinical trial of the antipsychotic agent cariprazine for the treatment of bipolar depression.

A total of 233 patients were randomized to enter one of two active (low dose or high dose) treatment arms or receive a placebo. The primary endpoint was the Montgomery-Asberg Depression Rating Scale (MADRS) score. Although the overall difference observed between the drugtreated and placebo-treated groups was not statistically significant, over the course of the trial there was evidence of a clinically relevant treatment effect in the high-dose arm of the study compared with placebo. Approximately 9 percent of patients discontinued the study early due to adverse events in the high-dose study arm compared with 3 percent in the placebo arm. The companies are considering conducting an additional phase 2 dose-response trial examining a wider range of doses.

Med Check

A large case-control study based on Danish birth and psychiatric records has added more evidence to back the theory that an association exists between mothers' infection with herpes simplex virus 2 (HSV-2) and the risk of schizophrenia in their children.
Data Show Reason for Concern if Mothers Carry Herpes Virus

Ботокс против головной боли

Botox Approved for Headache Prophylaxis in Chronic Migraine

Серотониновая система и шизофрения

Specifically, the study revealed that serotonin signals through the serotonin 2A receptor by recruiting a regulatory protein called β-arrestin2. The actions of serotonin at the receptor were found to be far different than those produced by hallucinogenic N-methyltryptamines, a class of naturally occurring substances found in several plants and in minute amounts in the human body.

These substances are also found in the abused drug DMT.

The N-methyltryptamines activate the serotonin 2A receptor independently of β-arrestin2, researchers said.

The serotonin and the N-methyltryptamines both produce what is known as a head twitch response in animal models. Researchers determined that any interruption in the exclusive serotonin pathway prevents that response to serotonin but has no effect on N-methyltryptamine-induced head twitches.

This difference in response points to a distinct divergence in the signaling pathways utilized by these two neurotransmitters.

“Despite the fact that they activate the same receptor, serotonin leads to the assembly of a number of proteins associated with the receptor that the metabolites of serotonin do not produce,” Bohn said. “But whether the lack of this complex formation is why compounds like DMT lead to hallucinations is not clear.”

Serotonin Discovery Points to New Therapies for Schizophrenia, Depression

пролонгированная форма рисперидона vs кветиапин

Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan–Meier estimate of time-to-relapse was significantly longer with RLAI (p < 0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

Relapse Prevention in Schizophrenia and Schizoaffective Disorder with Risperidone Long-Acting Injectable vs Quetiapine: Results of a Long-Term, Open-Label, Randomized Clinical Trial

Болезнь Хантингтона и каннабиноидная система

The biology of Huntington's is only partially understood. It's caused by mutations in the huntingtin gene, which lead to the build-up of damaging proteins in brain cells, especially in the striatum. But exactly how this produces symptoms is unclear.

The two new papers show that cannabinoids play an important role. First off, Van Laere et al used PET imaging to measure levels of CB1 receptors in the brain of patients in various stages of Huntington's. CB1 is the main cannabinoid receptor in the brain; it responds to natural endocannabinoid neurotransmitters, and also to THC, the active ingredient in marijuana.

They found serious reductions in all areas of the brain compared to healthy people, and interestingly, the loss of CB1 receptors occurred early in the course of the disease:

If so, drugs that activate CB1 - like THC - might be able to slow down the progression of the disease, and indeed it did: Huntington's mice given THC injections stayed healthier for longer, although they eventually succumbed to the disease. Further experiments showed that mutant huntingtin switches off expression of the CB1 receptor gene, explaining the loss of CB1.

Cannabinoids in Huntington's Disease

Поддерживающая терапия в комбинации с психосоциальным вмешательством

Xiaofeng Guo, M.D., and Jinguo Zhai, M.D., and colleagues evaluated this combination of therapies in 1,268 patients with early-stage schizophrenia treated from 2005 to 2007. A total of 633 were randomly assigned to receive schizophrenia drugs plus a psychosocial intervention involving 48 one-hour group sessions.

The psychosocial intervention included four evidence-based practices: psychoeducation (instruction for families and caregivers about mental illness), family intervention (teaching coping and socializing skills), skills training and cognitive behavioral therapy.

The other 635 patients received medication alone.

Rates of treatment discontinuation or change were 32.8 percent in the combined treatment group, compared with 46.8 percent in the medication-only group. The risk of relapse was lower among patients in the combination group, occurring in 14.6 percent of patients in that group and 22.5 percent of patients in the medication-only group.

The combined treatment group also exhibited greater improvements in insight, social functioning, activities of daily living and on four domains of quality of life, and a significantly higher proportion of them were employed or received education. There were no significant differences in either frequency or type of adverse events between the groups.

Early Meds, Counseling Aid Schizophrenia

Кетамин

Ketamine and the next generation of antidepressants with a rapid onset of action

Антидепрессивные свойства наркоза кетамином при ЭСТ

Background: Reports of the superiority of the antidepressant effect of ketamine during the conduct of electroconvulsive therapy (ECT) have been limited. We conducted an open-label trial of ketamine to determine whether ketamine as the anesthetic during ECT would provide a greater antidepressant effect than the antidepressant effect obtained with propofol.

Methods: Between April 2006 and April 2007, 31 inpatients with treatment-resistant depression gave written consent for ECT and to participate in this study. An anesthesiologist who was unaware of the mental symptoms of the subjects assigned them to receive propofol or ketamine anesthetic according to the preferences of the patients, and the patients underwent 8 ECT sessions for 4 weeks. The Hamilton Depression Rating Scale (HDRS) was valuated before ECT and after the completion of the second, fourth, sixth, and eighth ECT sessions.

Results: The HDRS scores improved earlier in the ketamine group, with decreases in HDRS scores that were significantly greater in the ketamine group.

Conclusions: The results suggested that it is possible to improve symptoms of depression earlier by using ketamine anesthesia.

Rapid Antidepressant Effect of Ketamine Anesthesia During Electroconvulsive Therapy of Treatment-Resistant Depression: Comparing Ketamine and Propofol Anesthesia

Индивидуальное дозирование антипсихотиков

Paralleling the preclinical evidence, are there clinical data to suggest antipsychotic tolerance with continuous treatment? Work with first-episode schizophrenia has confirmed three findings related to antipsychotic treatment: (a) response to lower doses; (b) sensitivity to side effects; and (c) comparatively high response rate.[2,21] In contrast, the more chronic stages of schizophrenia are associated with higher antipsychotic doses and diminished clinical response,[22,23] keeping in mind that the chronic population is more heterogeneous and includes a larger proportion of refractory patients who may be receiving higher doses. While antipsychotic tolerance has been raised to account for a progressive decline in response,[24] nonadherence and/or illness progression are routinely endorsed as more viable explanations. That as many as 25% of individuals on depot antipsychotic therapy relapse[25] tempers the nonadherence argument, but at the same time does not rule out alternative explanations, eg, a discrete breakthrough episode vs tolerance per se. In contrast, the preclinical description of behavioral dopamine supersensitivity closely parallels the notion of "supersensitivity psychosis" and withdrawal dyskinesias reported clinically, linked to D2 upregulation as a result of ongoing antipsychotic exposure and observed in the face of drug discontinuation.[26–28]

Antipsychotic Dosing: How Much but Also How Often?

илоперидон

Fanapt: Deconstructing A Promotional Slide Deck

Лоразепамовый тест

Case material and retrospective studies support the use of both lorazepam and ECT in treating catatonia, but few prospective investigations exist and none employ quantitative monitoring of response. In this study we test their efficacy in an open, prospective protocol, and define a "lorazepam test' with predictive value for treatment. Twenty-eight patients with catatonia were treated systematically with parenteral and/or oral lorazepam for up to 5 days, and with ECT if lorazepam failed. Outcome was monitored quantitatively during the treatment phase with the Bush-Francis Catatonia Rating Scale (BFCRS). In 16 of 21 patients (76%) who received a complete trial of lorazepam (11 with initial intravenous challenge), catatonic signs resolved. A positive response to an initial parenteral challenge predicted final lorazepam response, as did length of catatonic symptoms prior to treatment. Neither demographic variables nor severity of catatonia predicted response to lorazepam. Four patients failing lorazepam responded promptly to ECT. It is concluded that lorazepam and ECT are effective treatments for catatonia. The rating scale has predictive value and displays sensitivity to change in clinical status.

Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.

глутамат, допамин, шизофрения

The new findings unveil the fact that the high levels of dopamine found in people with psychotic symptoms actually occur as a result of changes in another brain chemical, glutamate.

Scientists discovered that brain cells that release glutamate in the hippocampus connect to the striatum and have a direct influence on the activity of dopamine-releasing cells.

Understanding Glutamate and Psychosis Offers Hope for Schizophrenia

шизовирус

TO THE EDITOR: The review article by Alan S. Brown, M.D., M.P.H., and Elena J. Derkits, B.A. (1), published in the March 2010 issue of the Journal, provided further evidence of a possible role of prenatal infection and maternal immune response in the etiology of schizophrenia. The authors also emphasized the importance of gene-environment interplay in neurodevelopmental disturbance leading to schizophrenia. However, the hypothesis of the single prenatal viral or immunological effect on the developing brain as a predisposing factor to schizophrenia cannot explain the variable long-term course of the illness.

A recent discovery of intracellular RNA-based gene inactivation machinery (short interfering RNA-induced silen cing complex) (2) suggested a mechanism of the natural defense against neurotropic viruses. RNA-induced silencing complex is the natural mechanism that prevents viruses from producing functional proteins. Such cellular defense can inhibit production of HIV and poliovirus (2–3). In some cases, the viral infection can be cleared; in other cases a virus can escape (4).

A hypothetical genetic variation in RNA-induced silencing complex may explain a variability of illness progression in schizophrenia: in some affected individuals, RNA-induced silencing complex controls an expression of schizovirus, while in others genetic polymorphism in RNA-induced silencing complex may lead to overstimulation of the cellular defense with temporary silencing of both schizoviral RNA and some host cell RNAs. Such dysregulation in the RNA-induced silencing complex response may increase dopamine production in affected neurons and lead to transient positive symptoms of schizophrenia, a clinical presentation consistent with "cycloid psychosis"(5). In some other patients, the underresponsive defense leads to a fast progression of neuronal damage and early development of deficit schizophrenia (6). In a majority of cases, overstimulation of RNA-induced silencing complex and eventual viral escape from the short interfering RNA inhibition is represented by often intermittent positive psychotic symptoms and progression of negative symptoms. Thus, suggested polymorphisms in the RNA-induced silencing complex genes may be related to genetic vulnerability to schizophrenia and a progression of the disease.

There is a lack of studies of RNA-induced silencing complex activity in humans. It is tempting, however, to suggest that a study of intracellular RNA defense may help to identify infectious agents, predisposing to schizophrenia, and that a development of short interfering RNA therapy may potentially cure some schizophrenia spectrum disorders.

Natural Antiviral Cellular Defense in Relation to Positive and Negative Symptoms of Schizophrenia?

Влияние гипертензии и индекса массы тела на когнитивные функции у больных шизофренией

Objective: In recent years there has been a greater appreciation of the elevated prevalence of cardiovascular risk factors in the schizophrenia population and the liability some treatments have for their development. These vascular risk factors are in turn important risk factors in the development of dementia and more subtle cognitive impairments. However, their impact on the cognitive functions of patients with schizophrenia remains underexplored. The authors investigated whether vascular risk factors influence the cognitive impairments of schizophrenia and whether their effects on cognition in schizophrenia are different from those observed in nonpsychiatric comparison subjects.

Method: The authors compared 100 patients with schizophrenia and 53 comparison subjects on cognitive test performance in 2x2 matrices composed of individual vascular risk factors and group (schizophrenia patients and comparison subjects).

Results: Hypertension exerted a significant negative effect on immediate delayed and recognition memory in both groups. Patients with schizophrenia and hypertension were adversely affected in recognition memory, whereas comparison subjects were not. A body mass index above 25 was associated with negative effects on delayed memory in both groups, although the association fell short of statistical significance.

Conclusions: Given that patients with schizophrenia have a higher prevalence of vascular risk factors than the general population and are undertreated for them, treatment of these risk factors may significantly improve cognitive outcome in schizophrenia.

The Effects of Hypertension and Body Mass Index on Cognition in Schizophrenia