Тиреоидная функция до и после лечения психотического эпизода

Background
Endocrine function in psychiatric patients may be affected by mental disorder itself as well as by antipsychotic medications.
The aim of this naturalistic observational study was to determine if treatment of acute psychotic episode with antipsychotic medication affects thyroid axis hormone concentrations and if such changes are associated with symptomatic improvement.
Methods
Eighty six adult acute psychotic patients, consecutively admitted to a mental hospital, were recruited for the study. All patients were physically healthy and without thyroid disease. During the hospitalization period all study patients received treatment with antipsychotic medication according to clinical need. Severity of the psychotic episode was evaluated using the Brief Psychiatric Rating Scale (BPRS) and venous blood samples were drawn for analysis of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations on the day of admission and on the day of discharge from the hospital.
Results
Antipsychotic drug treatment was associated with decrease of mean FT3 (p < 0.001) and FT4 (p = 0.002) concentrations; and with increase of mean TSH (p = 0.016) concentrations. Changes in thyroid hormone concentrations were mostly predicted by baseline hormone concentrations. Individual changes were not limited to decrease in high hormone concentrations; in patients who had low FT3 or FT4 concentrations, treatment resulted in increase in concentrations. Such an increase was established in one-quarter of patients for FT3 concentrations and in one-third of patients for FT4 concentrations. Fall in FT4 concentrations negatively correlated with the improvement in the BPRS score (r = −0.235, p = 0.023).
Conclusions
The study indicates that antipsychotic treatment resulted in a decrease in mean FT3 concentrations and in an increase in mean TSH concentrations after recovery from acute psychosis. Symptomatic improvement was less evident in patients who experienced a decrease in FT4 concentrations.

 Thyroid axis function after in-patient treatment of acute psychosis with antipsychotics: a naturalistic study

Антипсихотические свойства варфарина

Warfarin has been linked to a decrease in and even long-term remission of psychotic symptoms in patients with schizophrenia, preliminary research suggests.
A study examining adults at an anticoagulation clinic for deep venous thrombosis (DVT) showed that 5 patients who also had schizophrenia and who received long-term treatment with warfarin for recurrent DVT achieved full psychosis remission. In addition, these patients remained free of any psychotropic medication for 2 to 11 years.
The investigators note that the underlying mechanism could be tissue-plasminogen activator (tPA), a protein that not only promotes the dissolution of blood clots but also plays a role in neurogenesis after severe stress.

Warfarin for Long-term Psychosis Remission?

Механизм неврологических побочных эффектов сульфаниламидов

The team drew from previous research showing that blocking the activity of a certain enzyme (sepiapterin reductase) affects the levels of an important molecule called tetrahydrobiopterin (BH4) in cells. BH4 is critical for the production of neurotransmitters like serotonin and dopamine, and BH4 deficiency causes similar neurological problems to those associated with sulfonamide side effects. 

The EPFL scientists showed for the first time that sulfonamides actually bind to the part of the enzyme that makes BH4. Using a high-throughput drug screening system, the researchers identified ten sulfonamides that strongly inhibit the enzyme. Taking advantage of the expertise of Florence Pojer at EPFL's Global Health Institute, the scientists were able to solve the enzyme's molecular structure and determine how sulfonamides bind to it.

 New Understanding Of The Neurological Side Effects Of Sulfonamide Antibiotics

Взаимодействие рецепторов серотонина и глутамата как возможный механизм психоза

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

A Psychedelic Tale of Two Neurotransmitters

Случаи психиатрической манифестации рассеянного склероза

Psychiatric disturbances, such as psychosis, have been often described during the course of multiple sclerosis (MS),1 but rarely at onset of the disease.2 In our work, we present two patients with psychotic disorders at onset of relapsing-remitting MS.

The first patient, a 26-year-old woman, was diagnosed with schizoaffective disorder after the acute appearance of auditory hallucinations and confusion; she was treated with antipsychotic drugs, without significant results. One year later, the patient developed weakness in the left leg and widespread paraesthesia. MR images showed demyelinating lesions in the white matter of the left temporal horn and in the dorsal spine. We made a diagnosis of MS,3 and she started glatiramer acetate treatment to prevent further relapses. To date, after 12 months from the beginning of treatment, the patient shows no relevant neurological and psychiatric alterations.

The second patient, a 30-year-old man, presented (2 years before our observation) with an episode characterized by psychomotor agitation with identity disturbances diagnosed as borderline personality disorder, and he started treatment with olanzapine without results. After a few months, he was referred to our department because of the development of lower-limb weakness and urge-incontinence. An MRI showed several lesions in the subcortical white matter and in the periventricular regions. All findings supported the diagnosis of MS, and the patient started beta-interferon treatment, with progressive clinical improvement, both in neurological and then in psychiatric alterations.

The exact percentage of psychiatric onset of MS is still unknown, but the number of MS patients with psychiatric onset may exceed 1%: in our experience, 2 among a cohort of 148 MS subjects had a psychiatric onset, about 1.3%. In our two cases, only the presence of abnormalities at the neurological examination induced clinicians to consider MS as cause of psychiatric disturbance.

Several reports highlight the association of psychotic symptoms with the presence of demyelinating lesions in the left temporal lobe. In our patients, one had temporal lesions, and the other had periventricular plaques, without significant relationship with the temporal lobe. In our opinion, it is not possible to establish a direct relationship between the sites of cerebral lesions and the psychiatric manifestations observed in MS.

After the psychiatric episode, both patients started long-term treatment with glatiramer acetate or beta-interferon. As reported in literature, glatiramer acetate also results in relief of affective disorders,4 whereas beta-interferon increases anxiety and depression.5 Nevertheless, in our patient, the administration of beta-interferon probably contributed to stabilizing the clinical picture.

Although studies on the prevalence of psychiatric onset of MS are few, we conclude that it may occur in more than 1% (in our experience, about 1.3%) and that, in previously healthy people with acute psychotic disorders, even the presence of the slightest neurological abnormality justifies a cranial MRI examination. Further studies are necessary to evaluate the factors that influence the development of psychiatric disorders in MS and the relationship between disease-modifying drugs and psychiatric disorders.

Psychiatric Onset Of Multiple Sclerosis: Description Of Two Cases

Мета-анализ: каннабиноиды и риск психоза

Context A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness.

Objective To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis.

Data Sources Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non–substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science.

Study Selection Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non–substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria.

Data Extraction Information on study design, study population, and effect size were extracted independently by 2 of us.

Data Synthesis Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = –0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = –0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness.

Conclusions The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.

Cannabis Use and Earlier Onset of Psychosis

Болезнь Фабри и шизофреноформный психоз

A 21-year-old female with Fabry’s disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.

Fabry’s Disease and Psychosis: Causality or Coincidence?

Омега-3 ПНЖК в предупреждении развития психоза

Eighty-one putatively prodromal patients (16.4 years, 33.3% male) were included in this 12-month, randomized, double-blind, placebo-controlled trial comparing 1.2 g omega-3 PUFA (700 mg eicosapentaenoic acid [EPA] and 420 mg docosahexaenoic acid [DHEA]h) with placebo over 12 weeks with a follow-up of 40 weeks off medication/placebo. Randomization was stratified with regard to depressive symptoms (cut-off score on the Montgomery-Asberg Depression Rating Scale [MADRS]). Operationally defined conversion rates served as the outcome measure, with psychopathology ratings as secondary measures. Overall, this study had a very high 12-month completion rate (93.8%); adherence rates based on pill count and self-rating were as high as 81% and 75% in the active and placebo groups. The main result was that patients treated for 3 months with omega-3 PUFAs had significantly lower conversion rates to psychosis, at the end of the acute 3-month treatment phase and also after an additional 9 months off omega-3 PUFA (12-month conversion rate: 4.9% vs 27.5%). The number needed to treat (NNT) to prevent 1 additional patient with conversion to psychosis at 1 year was only 5. In addition, positive, negative, and general symptoms measured by the Positive and Negative Syndrome Scale (PANSS) were significantly more reduced in the active treatment group, whereas adverse events did not differ. Finally, the ratio of putatively beneficial omega-3 to omega-6 fatty acids increased significantly, linking the clinical effects to a proposed biological mechanism.

The Year in Psychosis and Bipolar Disorder: Omega-3s and Psychosis Prevention

Шизофреноподобный психоз при болезни Альцгеймера с ранним началом

Our patient was a 65-year-old right-handed woman. In August 2003, her family noticed her mild memory disturbance, and she developed delusions that someone intruded into her house, always watched her, and stole her bankbook. In March 2005, she developed auditory hallucinations that someone told her bad things. She also insisted that someone let snakes loose in her house and that someone hid himself under the stool and watched her. She was first diagnosed with schizophrenia and prescribed risperidone. At the next visit, the Mini-Mental Status Examination was administered and she scored 21/30. MRI showed mild diffuse brain atrophy, and SPECT showed right-dominant decreased rCBF in the temporoparietal lobe. Considering these results, her diagnosis was changed to early-onset Alzheimer’s disease. Donepezil was prescribed, and her psychoses were improved.

Schizophrenia-Like Psychosis and Dysfunction of the Right-Dominant Temporoparietal Lobe in Early-Onset Alzheimer’s Disease

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

Когнитивно-поведенческая терапия психозов

Beyond Antipsychotics: Using Cognitive Behavioral Therapy for Psychosis

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

Психиатрическая симптоматика при таламическом инфаркте

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

Риск обострения при отмене лекарств в зависимости от количества приступов шизофрении

This looks at the relapse risk over 5 years. These are remitted patients who go off medicines, and we're following them over time to see if their symptoms come back. Relapse was defined as rehospitalization, a very stringent criteria for relapse. And by 5 years, almost all patients had relapsed.

If you look at the group of patients who had had a first relapse and were followed out over time, 60 were at risk. Almost all had a second relapse, and then a third relapse was inevitable, happening more quickly. So relapse risk is very high, not necessarily in the first weeks after medication discontinuation or even in the first months, but over this time period symptoms will come back.

Enhancing Outcomes by Addressing Critical Challenges in the Treatment of Schizophrenia

Побочные эффекты при смене антипсихотиков

Психозы (феномены) «гиперчувствительности»
Клинически психозы гиперчувствительности проявляются обострением либо утяжелением симптомов психоза при назначении или смене антипсихотика. Первые клинические описания относятся к началу 60–х годов прошлого века, когда в начале нейролептической терапии на этапе титрации дозы у некоторых больных, преимущественно с органически неполноценной почвой и пожилых, отмечалось резкое усиление психоза. При этом в последующем, при увеличении дозы состояние, как правило, достаточно быстро стабилизировалось. В основе данного феномена – артефактное усиление дофаминовой трансмиссии вследствие ги­пер­чувствительности постсинаптических D2–рецеп­то­ров и увеличения их плотности. В последние годы данный клинический феномен регистрировался также при переводе с обычного антипсихотика (антагониста D2–рецепторов) на частичные агонисты дофамина. В данном случае механизм феномена гиперчувствительности несколько иной: высокий аффинитет к данному типу рецепторов и несколько иной профиль активности обусловливает вовлечение новых, ранее не задействованных рецепторов и частичное усиление синаптической трансмиссии в начале терапии.
Конечно, не каждое усиление психотических симптомов после перевода на новый препарат является феноменом гиперчувствительности. Четкая дифференциация с обострением психоза, безусловно, необходима. Одним из опорных признаков может быть тот факт, что риск обострения у стабильных больных низкий в первые 2–3 недели после отмены/перевода и повышается в последующие месяцы. Согласно данным многочисленных обсервационных исследований к факторам риска обострения следует отнести: мужской пол, молодой возраст, наличие органической почвы, зависимостей. Также выше риск обострения у стационарных и недавно стабилизированных пациентов, при резком обрыве терапии, предшествующей терапии высокими дозами АП и клозапином.
Терапевтическая тактика при психозах гиперчувствительности заключается в усилении антипсихотической терапии с быстрым повышением дозы. В то время как при переводе с D2–антагониста на частичный агонист тактика должна быть принципиально иной, с более медленной сменой антипсихотика.
«Ранняя активация» пациента при смене антипсихотика
«Ранняя активация» (РА) – достаточно часто используемое в последнее время определение в литературе. Следует отметить, наряду с «непривычностью» термина для психиатров, также отсутствие четкой клинической дефиниции. В целом под РА понимается развитие у пациента в начале новой антипсихотической терапии избытка энергии, повышенной активности, инсомнии. Традиционно данная симптоматитка рассматривалась как стимулирующий эффект нового препарата, что справедливо воспринимается, как нежелательное явление у психотических больных либо как признаки утяжеления психоза. Вместе с тем клинический феномен РА связан с отменой предшествующего антипсихотика и рассматривается исключительно как эффект отмены. Он связан с прекращением блокады гистаминовых ре­цепторов 1 типа (H1) и развивается при резкой отмене препаратов, фармакологический профиль которых характеризуется высокой активностью к данному типу рецепторов. К таким препаратам относятся большинство седативных (низкопотентных) антипсихотиков (хлорпромазин, левомепромазин и др.), а также оланзапин и клозапин. Безусловно, в каждом конкретном случае необходим дифференциальный диагноз РА с акатизией, возбуждением и собственно редукцией седативного эффекта.
Терапевтическая тактика заключается в более медленной смене терапии, назначении бензодиазепинов, в том числе в целях профилактики.

Оптимизация тактики смены антипсихотической терапии на модели кветиапина

ДСМ5: Синдром малой психотической симптоматики

Attenuated Psychotic Symptoms Syndrome

Ведение пациентов с первым приступом психоза

ВЕДЕНИЕ ПАЦИЕНТОВ С ПЕРВЫМ ПРИСТУПОМ ПСИХОЗА

продром, длительность нелеченного психоза, первый психотический эпизод

Most patients presenting to health services with an 'at risk mental state' will not develop psychosis. In the original Yung and McGorry study, transition rates were 40% over 12 months, but more recent studies found rates more in the vicinity of 15-30%. This still represents a level of risk increased a thousand-fold over the general population...
These early trials raise the possibility of primary or at least secondary prevention of psychotic disorders, although many questions remain. There are ethical issues in treating a group of people of whom 80% will not in any case progress to psychosis in the short term. Also, the base-rates, specificity and sensitivity of these at risk mental states in predicting psychosis may still mean this approach is of limited value at a population level...
Recovery rates from the first episode are high, with 85% achieving remission over a mean time of 3 months. Individuals in the first episode are sensitive both to the therapeutic effects and the adverse effects of antipsychotic drugs. This means they are more likely to respond to lower doses than in later episodes, but also are more susceptible to motor side effects. Most expert opinion advocates second generation antipsychotics as first line treatment (e.g. initially 0.5-2 mg risperidone or 2.5-7.5 mg olanzapine per day). Benzodiazepines are often used as adjuncts for agitation or catatonic symptoms. Poor adherence with treatment is if anything more problematic than at later stages of illness, since placebo controlled trials show a greater benefit of antipsychotics in first episode treatment and first relapse prevention yet up to 50% of individuals will be non-adherent in the first year. Cognitive behaviour therapy in addition to drug treatment is indicated.

Early Detection of Schizophrenia: Post-Detection: Early Treatments in the First Episode

Психозы гиперчувствительности, психозы "отдачи", поздние психозы

* Антиаритмические препараты могут провоцировать аритмии, антибиотики могут способствовоать развитию новых видов инфекций, а антипсихотические препараты могут вызывать психоз.
* Как мы можем отличить поздний психоз от шизофрении?
* Не является ли иногда резистентная шизофрения на самом деле поздним психозом?
* Снижает ли применение некоторых новых антипсихотиков вероятность развития позднего психоза?

АНТИПСИХОТИЧЕСКИЙ ПСИХОЗ

Сравнительная эффективность типичных и атипичных антипсихотиков в терапии первого психотического эпизода

Background

There is an ongoing debate about the use of atypical antipsychotics as a first-line treatment for first-episode psychosis.

Aims

To examine the evidence base for this recommendation.

Method

Meta-analyses of randomised controlled trials in the early phase of psychosis, looking at long-term discontinuation rates, short-term symptom changes, weight gain and extrapyramidal side-effects. Trials were identified using a combination of electronic (Cochrane Central, EMBASE, MEDLINE and PsycINFO) and manual searches.

Results

Fifteen randomised controlled trials with a total of 2522 participants were included. No significant differences between atypical and typical drugs were found for discontinuation rates (odds ratio (OR) = 0.7, 95% CI 0.4 to 1.2) or effect on symptoms (standardised mean difference (SMD) = –0.1, 95% CI –0.2 to 0.02). Participants on atypical antipsychotics gained 2.1 kg (95% CI 0.1 to 4.1) more weight than those on typicals, whereas those on typicals experienced more extrapyramidal side-effects (SMD = –0.4, 95% CI –0.5 to –0.2).

Conclusions

There was no evidence for differences in efficacy between atypical and typical antipsychotics, but there was a clear difference in the side-effect profile.

Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis