Амисульприд-индуцированная акатизия как маркер нарушения взаимоотношений серотонина и дофамина при ОКР

We report about a clinical observation in a well-characterized group of patients with obsessive–compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D2/3 antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive–compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine–serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction. We further speculate about the neuropathology possibly underlying this clinical observation and outline a testable hypothesis for future molecular imaging studies.

 Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine–serotonin interactions?

Предупреждение нежелательных эффектов лекарственных препаратов в психиатрии

How to prevent adverse drug events

Акатизия при отмене габапентина

OBJECTIVE: To report a case of akathisia in a patient with type 2 diabetes after abrupt discontinuation of gabapentin.

CASE SUMMARY: A 76-year-old female with type 2 diabetes was admitted for change in mental status, agitation, and restless limb movements. She had been taking gabapentin 3600 mg daily for approximately 1 month for diabetic neuropathy. Her other home medications were glyburide 10 mg twice daily, oxycodone/acetaminophen 5 mg/325 mg every 6 hours as needed for leg pain, and zolpidem 5 mg at bedtime. She had taken none of these drugs for 4 days prior to admission because she was unable to have the prescriptions refilled. Subsequently, the patient exhibited repeated arm and leg motions in response to an inner restlessness. Upon admission to the emergency department, she was agitated and restless; all vital signs and results of laboratory studies were within normal limits. Gabapentin was restarted at the original dosage and the symptoms resolved within 8 hours. Because the patient developed lethargy, the gabapentin dosage was reduced and titrated to the original level over 2 days. After 3 days, the patient was well oriented and experienced no further symptoms. She was discharged on the original dosage of gabapentin.

DISCUSSION: To our knowledge, this is the first reported cases of akathisia induced by gabapentin withdrawal. Available case reports suggest that gabapentin withdrawal can occur at doses ranging from 400-8000 mg/day. Patients experienced symptoms similar to those that develop with benzodiazepine withdrawal and were taking gabapentin for as little as 3 weeks to as long as 5 years. This is the first case report to describe akathisia induced by gabapentin withdrawal. The Naranjo probability scale revealed a probable relationship between akathisia and gabapentin withdrawal.

CONCLUSIONS: If gabapentin discontinuation is desired, it is prudent to gradually taper the dose to avoid withdrawal symptoms, which may occur after as little as 1 month of treatment. Should the patient experience withdrawal symptoms, the optimal treatment is to restart gabapentin.

Akathisia Induced by Gabapentin Withdrawal

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

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

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

Акатизия и атипичные антипсихотики

Akathisia and Second-Generation Antipsychotic Drugs

коррекция акатизии вызванной нейролептиками при помощи пиридоксина

his study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design.

The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037).
Vitamin B6 Treatment in Acute Neuroleptic-Induced Akathisia: A Randomized, Double-Blind, Placebo-Controlled Study.

Миртазапин в качестве корректора акатизии вызванной антипсихотиками

OBJECTIVE: To evaluate the role of mirtazapine in the treatment of antipsychotic-induced akathisia. DATA SOURCES: MEDLINE (1966-February 2008) and PsycINFO (1967-February 2008) were searched using the terms akathisia and mirtazapine. A bibliographic search was conducted as well. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the search were evaluated. All primary literature was included in the review. DATA SYNTHESIS: Antipsychotic-induced akathisia can be difficult to manage and may respond to mirtazapine based on its antagonist activity at the serotonin 5-HT(2A)/5-HT(2C) receptors. Three case reports (N = 9 pts.), 1 placebo-controlled trial (N = 26), and 1 placebo- and propranolol-controlled study (N = 90) that evaluated mirtazapine for antipsychotic-induced akathisia have been published. Mirtazapine demonstrated a response rate of 53.8% compared with a 7.7% response rate for placebo, based on at least a 2-point reduction on the Barnes Akathisia Scale (global subscale; p = 0.004). Using the same criterion, mirtazapine and propranolol demonstrated efficacy based on response rates of 43.3% and 30.0% compared with placebo (6.7%; p = 0.0051). Mirtazapine was better tolerated than propranolol. In both studies, drowsiness was the most common adverse event associated with mirtazapine. CONCLUSIONS: Mirtazapine may be considered a treatment option for antipsychotic-induced akathisia. It may be especially useful for patients with contraindications or intolerability to beta-blockers and for those with comorbid depression or negative symptoms. Additional studies should be conducted to provide further evidence of mirtazapine's effectiveness in treating akathisia.

pubmed

Абилифай и акатизия

Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder: A Second Multicenter, Randomized, Double-Blind, Placebo-Controlled Study



Adverse events (AEs) that occurred in >= 10% of patients with adjunctive placebo or adjunctive aripiprazole were akathisia (4.5% vs. 23.1%), headache (10.8% vs. 6.0%), and restlessness (3.4% vs. 14.3%).

The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study