Ранние предикторы последующей смены антипсихотика

Background

To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia.
Methods

This post-hoc analysis used data from a 1-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first 2 weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication.
Results

About one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the 1-year study. There were 6 variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first 2 weeks of antipsychotic therapy.
Conclusions

Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following 2 weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.

Predictors of switching antipsychotic medications in the treatment of schizophrenia

Клозапин

• Indian research: Focus on clozapine
• Relapse of tardive dyskinesia due to reduction in clozapine dose

Ошибочно диагностированная шизофрения у пациента с эпилепсией

One of the subjects that most concerns physicians is treatment-resistance. About 30%–60% of schizophrenia patients do not respond adequately to antipsychotic treatment and are known as refractory schizophrenia patients. Clozapine has been the drug of choice in such cases. However, approximately 30% of them do not respond to clozapine either. Here, we describe a patient with an initial diagnosis of refractory schizophrenia who had a history of dramatic aggressiveness. However, in this case, “refractoriness” was a wrong diagnosis. A case of psychosis secondary to epilepsy had been treated as schizophrenia for almost 20 years. Reports like this one are important because they remind us of how a thorough investigation can lead to the correct diagnosis and improve the patient's prognosis.

A False Case of Clozapine-Resistant Schizophrenia

CATIE

Когнитивно-поведенческая терапия психозов

Beyond Antipsychotics: Using Cognitive Behavioral Therapy for Psychosis

Пропранолол при ПТСР

The β-blocker propranolol may interrupt reconsolidation of traumatic memories through protein synthesis inhibition, presenting a promising treatment option for posttraumatic stress disorder (PTSD), 2 new studies suggests.
Propranolol blocks β-adrenergic receptors and, if administered after subjects have actively recalled their memory, may have a 6-hour window to interrupt memory reconsolidation.

Propranolol a Promising Treatment for PTSD

Once-Daily Gabapentin Effective for Postherpetic Neuralgia Pain and Sleep Disturbance

Нестандартные методы лечения аддикций

Virtual reality graded exposure
VRGET is a rapidly emerging technological intervention with a wide range of promising clinical applications for psychiatric disorders, including posttraumatic stress disorder, phobias, eating disorders, cognitive rehabilitation following stroke, and substance abuse and dependence. Most virtual reality tools are in the early stages of development and are not commercially available. VRGET protocols have been created with the goal of stimulating drug or alcohol craving in patients followed by response prevention and desensitization.

Nonconventional and Integrative Treatments of Alcohol and Substance Abuse

Таблицы влияния курения на концентрацию лекарственных средств

SMOKING AND DRUG INTERACTIONS

Подбор доз антипсихотиков второго поколения

Drug-drug interactions or genetic variability may require using doses different from those recommended for atypical antipsychotics. Dosage alterations of olanzapine and clozapine, dependent on cytochrome P450 1A2 (CYP1A2) for clearance, and quetiapine, dependent on cytochrome P450 3A (CYP3A), may be necessary when used with other drugs that inhibit or induce their metabolic enzymes. Smoking cessation can significantly increase clozapine, and perhaps olanzapine, levels. Ziprasidone pharmacokinetic drug-drug interactions are not likely to be important. Genetic variations of cytochrome P450 2D6 (CYP2D6) and drug-drug interactions causing inhibition (CYP2D6 and/or CYP3A) or induction (CYP3A) may be important for risperidone, and perhaps for aripiprazole, dosing. Adding inhibitors may cause side effects more easily in drugs with a narrow therapeutic window, such as clozapine or risperidone, than in those with a wide therapeutic window, such as olanzapine or aripiprazole. Adding inducers may be associated with a gradual development of lost efficacy.

The Dosing of Atypical Antipsychotics

Психические расстройства при злоупотреблении кофеином

Causes

* The means by which caffeine exerts its pharmacologic effects remains a subject of active research.
* A leading theory suggests that caffeine is an adenosine receptor antagonist that blocks 2 major types of adenosine receptors, A1AR and A2AAR.9
* Adenosine is an inhibitory neuromodulator affecting norepinephrine, dopamine, and serotonin activity.
* Caffeine's putative antagonism of adenosine would increase those neurotransmitters promoting psychostimulation.
* The same neurotransmitter systems are implicated in the pathophysiology of several psychiatric disorders.

Caffeine-Related Psychiatric Disorders

Курение и шизофрения

OBJECTIVE: Many case-control and cross-sectional studies have observed an association with cigarette smoking after the onset of schizophrenia, and there is evidence to suggest that smoking may improve symptoms in people with this disorder. Here, the authors investigated whether cigarette smoking alters the risk of subsequently developing schizophrenia. No longitudinal studies have previously examined this relationship. METHOD: A cohort of 50,087 Swedish conscripts (98% were ages 18–20) was followed up by record linkage to the National Register of Inpatient Care from 1970 to 1996 to determine hospital admission for schizophrenia. Cox regression was used to obtain hazard ratios and 95% confidence intervals (CIs) for schizophrenia, according to smoking status. RESULTS: Smoking cigarettes at ages 18–20 was associated with a lower rate of developing schizophrenia after adjustment for confounders. There was a linear relationship between the number of cigarettes smoked and a lower risk of schizophrenia (adjusted hazard ratio for linear trend across smoking categories, 0.8 [95% CI=0.7–0.9]), with an adjusted hazard ratio for heavy smokers of 0.5 (95% CI=0.3–0.9) compared to that of nonsmokers. This association persisted when analysis was restricted to subjects diagnosed after the first 5 years following conscription to reduce possible prodromal effects of schizophrenia on smoking. CONCLUSIONS: Cigarette smoking may be an independent protective factor for developing schizophrenia. These results are consistent with animal models showing both neuroprotective effects of nicotine and differential release of prefrontal dopamine in response to nicotine. The harmful effects of cigarette smoking vastly outweigh any possible benefits, but nevertheless, further investigation may lead to important insights regarding the etiology of schizophrenia at a molecular level.

Investigating the Association Between Cigarette Smoking and Schizophrenia in a Cohort Study

This higher ratio means that smokers need three to four times the caffeine "dosage" as nonsmokers on average to get the same plasma caffeine levels...
Thus smoking or caffeine intake should not influence the dosing of risperidone and aripiprazole (metabolized by CYP2D6 and CYP3A), quetiapine (mainly metabolized by CYP3A), and ziprasidone (mainly metabolized by an aldehyde oxidase and CYP3A). On the other hand, the metabolism of clozapine and olanzapine is mainly dependent on CYP1A2 and UGTs. Table 1 summarizes studies that describe smoking's effects on the dosing of clozapine and olanzapine. Because caffeine has the opposite effect of smoking and increases the levels of clozapine and olanzapine, studies of caffeine interactions are also reviewed in the table. The effects of caffeine on CYP1A2 are explained by competitive inhibition. The effects of inhibitors are seen sooner than those of inducers, which require CYP1A2 synthesis...
The width of the therapeutic window determines the clinical significance of the plasma level changes associated with smoking and caffeine intake. Compared with olanzapine, clozapine has a much narrower therapeutic window...
Table 1 provides an average smoking correction factor of 1.5 for clozapine. If a patient who is taking clozapine smokes, smoking cessation would probably cause an average patient's plasma clozapine level to increase by 1.5 two to four weeks later. Similarly, if a patient who is stabilized in a nonsmoking environment starts to smoke more than one pack a day, the clinician may need to consider increasing the clozapine dose by a factor of 1.5 over two to four weeks. Checking for side effects and measuring the clozapine level may then be prudent, because the 1.5 factor is a gross approximation.

Gender may also influence clozapine metabolism. The limited information available (3,4) suggests that an average female nonsmoker requires low clozapine dosages (around 300 mg per day) to reach therapeutic levels, whereas an average male heavy smoker requires high dosages (around 600 mg per day). The required dosages for male nonsmokers and female smokers fall in between these numbers. Obviously, these are average results and may not apply to specific individuals. In the future, it is hoped that a better understanding of genetics may help to individualize clozapine doses. A CYP1A2 genetic variation may influence how patients respond to smoking's inductive effects. However, in a recent study this variation did not have any effects on clozapine levels in the clinical environment (5).
Table 1 shows that the average caffeine correction factor is .6 for clozapine. Assuming other variables are stable, including no changes in smoking patterns, if a patient whose clozapine dose is stabilized in a caffeine-free environment begins to regularly consume high quantities of caffeine, it may be safest to decrease the clozapine dose—for example, from 400 to 250 mg a day (400 mg a day x .6=240 mg a day). Only high quantities of caffeine seem to have significant clinical interactions with clozapine.

In the United States, brewed coffee is estimated to contain 85 mg of caffeine per 5 oz cup; instant coffee, 65 mg per 5 oz cup; decaffeinated coffee, 3 mg per 5 oz cup; tea, 40 mg per 5 oz cup; and caffeinated sodas, including caffeinated colas, 40 mg per 12 oz can. In Europe, brewed coffee is estimated to contain more caffeine (100 mg per 150 cc cup). Obviously, caffeinated over-the-counter medicines in pill form may have much more caffeine than caffeinated beverages (up to 200 mg per pill). No data are available that show what level of caffeine intake is safe for patients who are taking clozapine. Steady caffeine dosages for a patient who is stabilized and is taking clozapine should not be of concern for clinicians. However, it may be important to warn the patient to avoid "dramatic" changes—either up or down —in caffeine intake. However, no published data define "dramatic" change in caffeine intake.
Psychopharmacology: Atypical Antipsychotic Dosing: The Effect of Smoking and Caffeine

Смертность пациентов с деменцией получающих антипсихотические препараты

They found that no antipsychotic was associated with greater long-term mortality, but that haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality during the first 30 days of prescribing.

Are Commonly Prescribed Antipsychotics Associated With Greater Mortality in Patients With Dementia?

Противосудорожные препараты и риск суицида

Suicide, Epilepsy-Drug Link Becomes a Little Clearer

Постинсультная депрессия

Box 2. Differential diagnosis of post-stroke depression.

Cognitive disorders following stroke Vascular dementia Frontal executive syndrome Memory deficit due to strategic infarctions Post-stroke attention deficit

Disorders of the perception of the self & the environment Anosognosia of hemiplegia Anosognosia of aphasia Affective dysprosodia

Post-stroke motivational syndromes Post-stroke apathy Loss of psychic autoactivation (athymhormia)

Disorders of emotional reactivity Blunted affect Involuntary emotional-expressive disorder Catastrophic reactions

Other post-stroke affective disorders Irritability and mania

Adaptative & post-traumatic disorders following stroke Coping disturbances following stroke Post-stroke personality changes Post-stroke fatigue Post-stroke sleeping disorders

Nevertheless, data from a recent Cochrane review concluded that there is no evidence for a significant effect of psychoactive treatment to prevent PSD, although the overall rate of depression was lower among patients treated with antidepressant drugs.[101]

Hackett et al. evaluated 14 randomized controlled trials that included more than 1500 patients. Data were available from ten pharmaceutical trials and four psychotherapy trials (psychotherapy against standard care or attention control) to prevent depression in patients with stroke. Heterogeneity and variability in evaluation methods, time of assessment, time from stroke onset to entry into the trial, treatment duration, chosen drugs and main outcomes were observed. Drugs assessed were fluoxetine, trazodone, piracetam, mianserin, nortriptyline, maprotiline, indeloxazine and methylphenidate. There was no clear effect of pharmacological therapy on the prevention of depression or other end points. The conclusion of this meta-analysis is that more evidence is required before recommendations can be made about the routine use of preventive treatments after stroke. In addition, authors recommend that antidepressants and psychostimulants should not be used to prevent PSD.[101]

Recently, a randomized controlled trial for the prevention of depression among 176 nondepressed patients was conducted within 3 months following an acute stroke. The authors assessed whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke would decrease the number of depression cases compared with placebo. The use of escitalopram resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo.[99] Nevertheless, this study caused several controversies, since some issues may limit the generalization of their results. Discrepancies were related to the low mean age of the sample, mainly in the escitalopram-treated group, the unusually high percentage of patients with bilateral white matter lesions (28% of the sample), and the degree of disability, which was low in this series.

Post-Stroke Depression: Can Prediction Help Prevention?: Differential Diagnosis

Транквилизаторы и риск преждевременной смерти

Use of sleeping pills and minor tranquilizers increases the risk of premature death by more than a third after controlling for a range of potentially confounding factors including depression, according to a study published in the September issue of the Canadian Journal of Psychiatry.

More Evidence Sedatives May Raise Risk of Premature Death

Сертралин

Sertraline Hydrochloride Tablet

Роль аппетита в прогнозе набора массы тела при терапии оланзапином

Early weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales.

The potential role of appetite in predicting weight changes during treatment with olanzapine

Психообразование в семьях больных шизофренией

Issues in Family Services for Persons With Schizophrenia

Акампросат

Acamprosate May Be Helpful to Treat Alcohol Dependence

Сердаксин

A new drug slated to undergo clinical study for major depressive disorder (MDD) shows promise for delivering the needed therapeutic effect to patients without triggering some of the more common side effects associated with anti-depressants.

Specifically, the drug provides a unique method of action that works as a dual enhancer of serotonin and dopamine in the brain.

Phase IIb Study of Serdaxin Underway for Treatment of Major Depressive Disorder

Луразидон

Lurasidone is simply another antipsychotic—no more, no less. The two major clinical trials (Pearl 1 and Pearl 2) have shown inconsistent efficacy results, high rates of side effects such as akathisia (restlessness), parkinsonism (tremor and stiffness), and sedation, and apparent inferiority to Zyprexa. Like several of the newer antipsychotics (such as Ability, Geodon, and Fanapt), Lurasidone causes little weight gain and few metabolic abnormalities. With no clear advantages over its many competitors, Lurasidone will succeed or fail based purely on the strength of its promotional campaign.

Stephen Stahl + Lurasidone: The Hired Guns Come to Town

LURASIDONE DEMONSTRATED EFFICACY IN TREATING PATIENTS WITH SCHIZOPHRENIA IN PIVOTAL PHASE 3 STUDY

Dainippon Sumitomo Pharma Announces Lurasidone Phase III Data In Patients With Schizophrenia

Профилактика депрессий при лечении гепатита C, неэффективность циталопрама

BACKGROUND: Approximately one-third of patients undergoing interferon-{alpha} (IFN-{alpha}) therapy for treatment of the hepatitis C virus (HCV) develop major depression, which decreases functioning and may lead to the reduction or discontinuation of treatment. OBJECTIVE: The authors examined the efficacy of citalopram in preventing IFN-{alpha}-induced depression in HCV patients. METHOD: This was a randomized, controlled trial comparing citalopram with placebo in 39 HCV patients. RESULTS: The rate of IFN-{alpha}-induced depression in the sample was 15.4% (6/39). Randomization to citalopram did not decrease the statistical likelihood of developing IFN-{alpha}-induced depression (10.5% for citalopram vs. 20.0% for placebo). CONCLUSION: Citalopram does not prevent depression onset; however, an empirically-supported treatment recommendation for IFN-{alpha}-induced depression includes monitoring depressive symptoms throughout antiviral therapy and initiating psychiatric treatment at the initial signs of depression.

Prophylactic Antidepressant Treatment in Patients With Hepatitis C on Antiviral Therapy: A Double-Blind, Placebo-Controlled Trial

Трансдермальный эстрадиол для лечения послеродовой депрессии

Transdermal estradiol for postpartum depression: A promising treatment option

Suicide Intent Scale

Objective Circumstances Related to Suicide Attempt
1. Isolation
1. Somebody present
2. Somebody nearby, or in visual or vocal contact
3. No one nearby or in visual or vocal contact

2. Timing
1. Intervention is probable
2. Intervention is not likely
3. Intervention is highly unlikely

3. Precautions against discovery/intervention
1. No precautions
2. Passive precautions (as avoiding other but doing nothing to prevent their intervention; alone in room with unlocked door)
3. Active precautions (as locked door)

4. Acting to get help during/after attempt
1. Notified potential helper regarding attempt
2. Contacted but did not specifically notify potential helper regarding attempt
3. Did not contact or notify potential helper

5. Final acts in anticipation of death (will, gifts, insurance)
1. None
2. Thought about or made some arrangements
3. Made definite plans or completed arrangements

6. Active preparation for attempt
1. None
2. Minimal to moderate
3. Extensive

7. Suicide Note
1. Absence of note
2. Note written, but torn up; note thought about
3. Presence of note

8. Overt communication of intent before the attempt
1. None
2. Equivocal communication
3. Unequivocal communication

Self Report
9. Alleged purpose of attempt
1. To manipulate environment, get attention, get revenge
2. Components of above and below
3. To escape, surcease, solve problems

10. Expectations of fatality
1. Thought that death was unlikely
2. Thought that death was possible but not probable
3. Thought that death was probable or certain

11. Conception of method's lethality
1. Did less to self than s/he thought would be lethal
2. Wasn't sure if what s/he did would be lethal
3. Equaled or exceeded what s/he thought would be lethal

12. Seriousness of attempt
1. Did no seriously attempt to end life
2. Uncertain about seriousness to end life
3. Seriously attempted to end life

13. Attitude toward living/dying
1. Did not want to die
2. Components of above and below
3. Wanted to die

14. Conception of medical rescuability
1. Thought that death would be unlikely if he received medical attention
2. Was uncertain whether death could be averted by medical attention
3. Was certain of death even if he received medical attention

15. Degree of premeditation
1. None; impulsive
2. Suicide contemplated for three hours of less prior to attempt
3. Suicide contemplated for more than three hours prior to attempt

Other Aspects (Not included in total score)
16. Reaction to attempt
1. Sorry it was made; feels foolish; ashamed
2. Accepts both attempt and failure
3. Regrets failure of attempt

17. Visualization of death
1. Life after death, reunion with descendants
2. Never-ending sleep, darkness, end of things
3. No conceptions of or thoughts about death

18. Number of previous attempts
1. None
2. One or two
3. Three or more

19. Relationship between alcohol intake and attempt
1. Some alcohol intake prior to but not related to attempt; reportedly not enough to impair judgment, reality testing
2. Enough alcohol intake to impair judgment; reality testing and diminish responsibility
3. Intentional intake of alcohol in order to facilitate implementation of attempt

20. Relationship between drug intake and attempt
1. Some drug intake prior to but not related to attempt; reportedly not enough to impair judgment, reality testing
2. Enough drug intake to impair judgment; reality testing and diminish responsibility
3. Intentional intake of drug in order to facilitate implementation of attempt


15-19 Low Intent
20-28 Medium Intent
29+ High Intent
There is also a greater risk of repeated attempts the higher the intent rating.

The Question of Intent in Suicide Attempts

Психиатрическая симптоматика при таламическом инфаркте

Persisting childish behavior after bilateral thalamic infarcts.
Thalamo-frontal psychosis.

Инверсия аффекта - дозозависимый эффект бупропиона

A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.

Mania with bupropion: a dose-related phenomenon?

Распространённость и факторы риска развития маниакальных и гипоманиакальных состояний при терапии антидепрессантами

Antidepressant-induced manias have been reported with all major antidepressant classes in a subgroup of about 20-40% of bipolar patients. Lithium may confer better protection against this outcome when compared with other standard mood stabilizers, although switch rates have been reported with comparable frequencies on or off mood stabilizers. Evidence across studies most consistently supports an elevated risk in patients with (i) previous antidepressant-induced manias, (ii) a bipolar family history, and (iii) exposure to multiple antidepressant trials.

ANTIDEPRESSANT-INDUCED MANIA: AN OVERVIEW OF CURRENT CONTROVERSIES

Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008).

Antidepressant-induced mania in bipolar patients: identification of risk factors.

Antidepressant-induced mania or hypomania was evident in 39.6% (21/53) of the study group. Patients who developed manic features soon after starting an antidepressant had more antidepressant trials per year than those who did not (p < .05). A history of substance abuse and/or dependence was associated with substantially increased risk for antidepressant-induced mania (odds ratio = 6.99, 95% CI = 1.57 to 32.28, p = .007). Concomitant mood stabilizers were not uniformly associated with protection against inductions of mania during antidepressant trials.

The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study

Аффективные расстройства лекарственного генеза

Causes

* Drugs with evidence of a link to depression or mania include the following:
o Flunarizine - Epidemiologic survey, adverse effect noted in several clinical trials
o Corticosteroids - Prospective cohort study, cross-sectional medicine patients
o Digoxin - Prospective cohort study, cross-sectional epidemiologic study
o Minor tranquilizers - Prospective cohort study
o Sedatives - Prospective cohort study
o Interferon beta-1b, peginterferon alfa-2b - Very significantly increased incidence in randomized controlled trials (RCTs), although trials were not designed to study this as an endpoint
o Amantadine - Increased incidence in RCTs, although trials were not designed to study this as an endpoint
o Isocarboxazid - Increased incidence in RCTs, although trials were not designed to study this as an endpoint
o Levetiracetam - Increased incidence in RCTs, although trials were not designed to study this as an endpoint

* Drugs with weak or conflicting evidence of a link to depression or mania include the following:
o ACE inhibitors - Prescription sequence symmetry analysis
o Propranolol and nadolol (ie, lipophilic beta-blockers) - Meta-analysis of antihypertensive clinical trials, record linkage studies
o Norplant - Series of case reports
o Leuprolide - Case series
o Isotretinoin - Case reports
o Antidepressants (ie, citalopram, bupropion, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, sertraline, venlafaxine) - Case reports

Differential Diagnoses

Adjustment Disorders
Alcoholism
Anxiety Disorders
Dysthymic Disorder
Hypothyroidism
Other Problems to Be Considered

Adrenal Insufficiency and Adrenal Crisis
Delirium, Dementia, and Amnesia

Substance-Induced Mood Disorders, Depression and Mania

Кетогенная диета и модифицированная диета Аткинса в лечении абсансной эпилепсии

Two high-fat diets — the classic ketogenic and a modified version of the Atkins — can be useful in difficult-to-treat absence epilepsy, report researchers.

Ketogenic and Atkins Diets Effective in Absence Epilepsy

Некоторые актуальные теоретические проблемы диагностики, классификации, нейробиологии и терапии шизофрении: сравнение зарубежного и отечественного подходов

Волосы как биомаркер стресса и сердечных заболеваний

Cortisol is considered to be a stress hormone. Its secretion is increased during times of stress.

Traditionally it’s been measured in serum, urine and saliva, but that only shows stress at the time of measurement, not over longer periods of time. Cortisol is also captured in the hair shaft.

Koren and Uum believe hair analysis can provide an accurate assessment of stress levels in the months prior to an acute event such as a heart attack.

“We know that on average, hair grows one centimetre (cm) a month, and so if we take a hair sample six cm long, we can determine stress levels for six months by measuring the cortisol level in the hair.”

Hair as Biomarker of Stress and Heart Disease

Ингибиторы ацетилхолинэстеразы при зрительных галлюцинациях

Background

Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition.
Methods

A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia.
Results

No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group.
Discussion

Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly.
Conclusions

We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: A review of the literature

Background

Visual hallucinations are commonly seen in various neurological and psychiatric disorders including schizophrenia. Current models of visual processing and studies in diseases including Parkinsons Disease and Lewy Body Dementia propose that Acetylcholine (Ach) plays a pivotal role in our ability to accurately interpret visual stimuli. Depletion of Ach is thought to be associated with visual hallucination generation. AchEI's have been used in the targeted treatment of visual hallucinations in dementia and Parkinson's Disease patients. In Schizophrenia, it is thought that a similar Ach depletion leads to visual hallucinations and may provide a target for drug treatment
Case presentation

We present a case of a patient with Schizophrenia presenting with treatment resistant and significantly distressing visual hallucinations. After optimising treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to treat her symptoms successfully.
Conclusions

This case is the first to illustrate this novel use of an AchEI in the targeted treatment of visual hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can be considered in challenging cases although more evidence is required in this field.

Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: A case report.

Риск шизофрении и уровень витамина D у младенцев

Both low and high concentrations of neonatal vitamin D are associated with increased risk of schizophrenia, and it is feasible that this exposure could contribute to a sizeable proportion of cases in Denmark. In light of the substantial public health implications of this finding, there is an urgent need to further explore the effect of vitamin D status on brain development and later mental health.

Neonatal Vitamin D Status and Risk of Schizophrenia

Монотерапия антипсихотиками vs комбинация с психосоциальным вмешательством

Compared with those receiving medication only, patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change, a lower risk of relapse, and improved insight, quality of life, and social functioning.

Effect of Antipsychotic Medication Alone vs Combined With Psychosocial Intervention on Outcomes of Early-Stage Schizophrenia

Плавная vs резкая отмена антидепрессантов

Rapid discontinuation was associated with a significantly shorter time to relapse than gradual discontinuation (median, 3.6 vs. 8.4 months). The authors estimated that time to relapse after rapid discontinuation was only 25% of the average time to earlier relapses in the same patients. The findings were most evident for bipolar I and panic disorders. After rapid discontinuation, the intervals preceding relapse were similar among different drug types, but after gradual discontinuation, time to relapse was substantially longer with tricyclics than with modern antidepressants. Relapse risk was the least pronounced for medications with prolonged half-lives and was not associated with antidepressant dose, duration of illness or treatment, or concurrent treatment.

Rapid vs. Gradual Discontinuation of Antidepressants

Psychological Science: Schizophrenia

Mycobacterium vaccae

Согласно результатам исследования, представленным на прошедшем в мае 2010 г. 110 съезде Американского общества по микробиологии (Сан-Диего, Калифорния), контакт с определёнными видами бактерий, присутствующими в окружающей среде, может приводить к улучшению настроения и повышению способности к обучению.

Группа исследователей под руководством D. Matthews занималась изучением Mycobacterium vaccae — микобактерии, которая в естественных условиях обитает в почве и может попадать в организм человека через пищеварительный тракт или дыхательные пути при нахождении на природе.

Могут ли бактерии сделать нас умнее?

Генотипы CYP450 и эффекты антипсихотиков

Metabolism of most antipsychotics depends on the CYP450 enzyme system, which is expressed predominantly in the liver (Table 1). CYP2D6 is one of these enzymes and may be responsible for metabolizing approximately 20% to 50% of all medications, including a number of antipsychotics.2 Genetic variations of CYP2D6 are common and the frequencies of these variants differ among racial groups.3

The half-life and other pharmacokinetic parameters of an antipsychotic metabolized by CYP2D6 may differ based on whether someone is a poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM), or ultrarapid metabolizer (UM).4 Regarding CYP2D6 metabolism among Whites, 3% to 5% are UMs, 70% to 80% are EMs, 10% to 17% are IMs, and 5% to 10% are PMs.5 By contrast, the percentage of PMs and UMs in the Asian population is low—about 1% for each phenotype; the IM phenotype is more common (65% to 70% in the Chinese population).5,6 The percentage of PMs in African Americans is roughly 2% to 6%.2

Cytochrome P450 (CYP) metabolism of commonly used antipsychotics*

Drug	CYP1A2	CYP2C9	CYP2C19	CYP2D6	CYP3A4/5
Aripiprazole				X	X
Asenapine	X			X	X
Chlorpromazine	X			X	X
Clozapine	X	X	X	X	X
Fluphenazine				X
Haloperidol	X			X	X
Iloperidone				X	X
Olanzapine	X			X
Paliperidone				X†	X†
Perphenazine	X	X	X	X	X
Quetiapine				X	X
Risperidone				X	X
Thioridazine			X	X
Ziprasidone	X				X
*Information obtained from the most recent prescribing information available from each drug’s manufacturer †According to paliperidone’s prescribing information, in vitro studies identify that CYP2D6 and CYP3A4 may be involved in paliperidone metabolism, but in vivo studies indicate that their role in eliminating paliperidone is minimal

Figure: Effects of CYP2D6 poor metabolizer status on the half-life of risperidone, aripiprazole, and iloperidone

EM: extensive metabolizer; PM: poor metabolizer
Source: References 7-9

It is not known if obtaining genotype information will provide better outcomes than a ‘trial and error’ approach

Should you order genetic testing to identify how patients metabolize antipsychotics?

Биомаркеры злоупотребления алкоголем

‘I’m sober, Doctor, really’: Best biomarkers for underreported alcohol use

Нелекарственные методы лечения инсомнии

Stimulus control therapy. Bootzin et al5 first evaluated stimulus control therapy for conditioned insomnia (subsequently identified as primary insomnia). This therapy’s goal is to interrupt the conditioned activation that occurs at bedtime. Patients are instructed to:

*

go to bed when sleepy
*

remain in bed for no more than 10 minutes (20 minutes if elderly) without sleeping
*

if unable to sleep, get up, do something boring, and return to bed only when sleepy
*

repeat getting up and returning as frequently as necessary until sleep onset.

For the first 2 weeks of stimulus control therapy, patients are required to self-monitor their sleep behaviors using a sleep diary. Stimulus control therapy is beneficial for primary insomnia and insomnia related to anxious preoccupation. About 70% of patients with conditioned insomnia will improve using stimulus control therapy,4 but it is not clear whether the primary effective intervention is:

*

patients dissociating conditioned responses at bedtime, or
*

the inevitable sleep restriction caused by getting out of bed.

Relaxation training. Progressive muscle relaxation is a common behavioral treatment of insomnia. Patients learn to tense and then relax individual muscles, beginning at the feet or head and working their way up or down the body. Patients are taught the difference between tension and relaxation to facilitate a relaxation response at bedtime. Another method is the body scanning technique, in which the patient “talks” to each body part, telling it to “relax… relax… relax.”

Relaxation training is predicated on the belief that insomnia is caused by somatized tension and psychophysiologic arousal. The greatest challenge to effective relaxation training is that patients need extensive daytime practice before they can bring the method to the bedroom.

Remind patients that “practice makes perfect.” Therapists often instruct patients to start practicing their relaxation method during the day while self-monitoring by sleep diary and restricting time in bed at night.2

CBTi is the most extensively investigated nonpharmacologic therapy for insomnia.6 It has been used to effectively manage comorbid insomnia in patients with psychiatric disorders,7,8 such as depression,9 generalized anxiety,10 and alcohol dependence,11 as well as those with breast cancer,12 traumatic brain injury,13 and fibromyalgia.14 Age does not appear to be a limitation; research trials show the technique is effective in elderly patients.15

CBTi incorporates cognitive strategies and behavioral interventions to improve sleep quality. Patient self-monitoring with sleep diaries and worksheets is essential.

CBTi commonly is provided in 5 to 8 sessions over 8 to 12 weeks, although studies have described abbreviated practices that used 2 sessions16 and CBTi delivered over the Internet.17 Highly trained clinical psychologists are at the forefront of therapy, but counselors and nurses in primary care settings have administered CBTi.18 For primary insomnia, CBTi is superior in efficacy to pharmacotherapy:

*

as initial treatment19
*

for long-term management4
*

in assisting discontinuation of hypnotic medication.20

Put your patients to sleep: Useful nondrug strategies for chronic insomnia

Вакцина от кокаиновой зависимости

Cocaine is a very simple molecule, but you can attach a simple molecule to a complex molecule and still trigger the immune system. You can use this method to develop antibodies to cocaine. When an individual uses cocaine, the antibodies will bind to the cocaine in the blood stream and the drug never reaches the brain because the molecule is now too large to pass the blood-brain barrier.

Pharmacotherapy for cocaine dependence: Most evidence is weak

Study	Design	Results
Disulfiram
Pani et al, 20108	Meta-analysis of 7 studies with 492 cocaine-dependent patients	Researchers found ‘low evidence’ supporting disulfiram for treating cocaine dependence
Modafinil
Dackis et al, 20059	62 cocaine-dependent patients randomized to modafinil, 400 mg/d, or placebo for 8 weeks	Patients receiving modafinil provided significantly more BE-negative urine samples and were significantly more likely to achieve ≥3 weeks of cocaine abstinence
Anderson et al, 200910	210 cocaine-dependent patients randomized to modafinil, 200 mg/d or 400 mg/d, or placebo for 12 weeks	Modafinil significantly reduced cocaine craving but did not significantly improve the average weekly percentage of cocaine non-use days
Tiagabine
Winhusen et al, 200711	141 cocaine-dependent patients randomized to tiagabine, 20 mg/d, or placebo for 12 weeks	No significant changes in cocaine use vs placebo as measured by self-report and urine BE
Baclofen
Kahn et al, 200912	Cocaine-dependent patients randomized to baclofen, 60 mg/d, or placebo for 8 weeks	No significant difference between groups in cocaine use as measured by urine BE
Ondansetron
Johnson et al, 200613	63 cocaine-dependent patients randomized to ondansetron, 0.25 mg, 1 mg, or 4 mg twice daily, or placebo for 10 weeks	The odansetron 4 mg group had a significantly greater rate of improvement in percentage of patients with a cocaine-free week compared with the placebo group
BE: benzoylecgonine

Vaccine for cocaine addiction: A promising new immunotherapy

Рекомендации по лечению инсомнии и других расстройств сна

Recommendations for Diagnosis and Treatment

Specific evidence-based recommendations for diagnosis and treatment of insomnia and other sleep disorders, and their accompanying level of evidence rating, are as follows:

* The diagnosis of insomnia is primarily based on complaints provided in the clinical interview by the patient, family, and/or caregiver, ideally corroborated by a patient diary (level of evidence, A).
* Referral to a specialist sleep center may be indicated for other tests in some cases, such as actigraphy for differential diagnosis of circadian rhythm disorder (level of evidence, A), polysomnography for suspected parasomnia or other primary sleep disorder (level of evidence, A), or in the case of treatment failure (level of evidence, D).
* Insomnia should be treated because it impairs quality of life and many areas of functioning and is associated with an increased risk for depression, anxiety, and possibly cardiovascular disorders (level of evidence, A). Treatment goals are to reduce distress and to improve daytime function. Choice of treatment modality is based on the particular pattern of problem, such as sleep-onset insomnia or sleep maintenance, as well as on the evidence supporting use of specific treatments.
* For chronic insomnia, cognitive behavioral therapy (CBT)-based treatment packages are effective and should be offered to patients as a first-line treatment (level of evidence, A). CBT, which may include sleep restriction and stimulus control, should be made available in more settings.
* When prescribing hypnotic drug treatment, clinicians need to consider efficacy, safety, and duration of action (level of evidence, A). Other issues to consider may include previous efficacy or adverse effects of the drug and history of substance abuse or dependence (level of evidence, D).
* Recommendations for long-term hypnotic drug treatment are to use it as clinically indicated (level of evidence, A). To discontinue long-term hypnotic drug therapy, intermittent use should first be attempted if feasible. Depending on ongoing life circumstances and patient consent, discontinuation should be attempted every 3 to 6 months or at regular intervals (level of evidence, D). During taper of long-term hypnotic drug treatment, CBT improves outcome (level of evidence, A).
* When using antidepressants, clinicians should apply their knowledge of pharmacology (level of evidence, A). When there is a comorbid mood disorder, antidepressants should be used at therapeutic doses (level of evidence, A). However, clinicians should beware that overdose of tricyclic antidepressants can be toxic even when low-unit doses are prescribed (level of evidence, A).
* Because of frequent adverse effects of antipsychotic drugs, as well as a few reports of abuse, there is no indication for use as first-line treatment of insomnia or other sleep disorders (level of evidence, D).
* Antihistamines have a limited role in psychiatric and primary care practice for the management of insomnia (level of evidence, D).

New Guidelines Issued for Insomnia and Other Sleep Disorders

Шизофрения у пожилых

Lowering the anticholinergic load is a key component of treating older schizophrenia patients

Schizophrenia in older adults

Исследование SAM-e при депресии

A total of 73 adults were enrolled in this six-week study and randomly assigned to the placebo control group or the SAM-e treatment group.

SAM-e, in combination with standard depression treatment, was more effective than antidepressant treatment alone in improving measures of depression and remission rates of patients with significant clinical depression. SAM-e-treated subjects had a greater response and remission rate to treatment than the placebo-treated group. SAM-e was well-tolerated with no reported adverse reactions.

Dietary Supplement SAM-e Aids Treatment of Depression

Механизм антидепрессивного действия кетамина

The Mechanism Behind Fast-Acting Antidepressant Ketamine

Самоповреждения, эмоции, brain imaging

Why Self-Harm Feels Good in the Brain

Эффективность антидепрессантов в лечении негативной симптоматики при шизофрении

Background

Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.

Aims

To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.

Method

Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.

Results

There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (–0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.

Conclusions

Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

Семейная история тревожных и депрессивных расстройств и утренний уровень кортизола

Background

It is unclear whether altered hypothalamic–pituitary–adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state factor.

Aims

To examine whether HPA axis dysregulation represents a biological vulnerability for these disorders, we compared cortisol levels in unaffected people with and without a parental history of depressive or anxiety disorders. We additionally examined whether possible HPA axis dysregulations resemble those observed in participants with depression or anxiety disorders.

Method

Data were from the Netherlands Study of Depression and Anxiety. Within the participants without a lifetime diagnoses of depression or anxiety disorders, three groups were distinguished: 180 people without parental history, 114 with self-reported parental history and 74 with CIDI-diagnosed parental history. These groups were additionally compared with people with major depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary cortisol samples were obtained upon awakening, and 30, 45 and 60 min later.

Results

As compared with unaffected participants without parental history, unaffected individuals with diagnosed parental history of depression or anxiety showed a significantly higher cortisol awakening curve (effect size (d) = 0.50), which was similar to that observed in the participants with depression or anxiety disorders. Unaffected people with self-reported parental history did not differ in awakening cortisol levels from unaffected people without parental history.

Conclusions

Unaffected individuals with parental history of depression or anxiety showed a higher cortisol awakening curve, similar to that of the participants with depression or anxiety disorders. This suggests that a higher cortisol awakening curve reflects a trait marker, indicating an underlying biological vulnerability for the development of depressive and anxiety disorders.
Parental history of depression or anxiety and the cortisol awakening response

Пернициозная анемия в форме кататонии без признаков анемии и макроцитоза

Pernicious anaemia can present with psychiatric symptoms before haematological or neurological manifestations appear. We describe a young woman who presented with insidious onset catatonia without evidence of psychosis or depression. Blood count and mean cell volume were normal and neurological findings were equivocal. Low B12 levels and intrinsic factor antibodies were found only by chance when they were included in a battery of further investigations. B12 replacement was followed by prompt improvement. This case provides an argument for wider screening for B12 deficiency in certain individuals with psychiatric disorders.

Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis

Болезнь Паркинсона, иммунная система, воспаление

The team confirmed that a gene in the human leukocyte antigen (HLA) region was strongly linked with Parkinson’s disease; this region contains a large number of genes related to immune system function...
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are protective against Parkinson’s disease, according to the study.

However, not everyone benefits from them to the same degree. The amount of risk reduction conferred by NSAIDs may vary widely depending on genetic differences, say the researchers.

Investigating the connection between Parkinson’s disease and inflammation, especially in the context of the variable genetic makeups of individuals, likely would lead to better, more selective medicines for treatment.

Parkinson’s May Be Linked to Immune System