Межлекарственные взаимодействия психотропных препаратов

1. СРИ на тему: «Межлекарственные взаимодействия психотропных препаратов»

ГОСУДАРСТВЕННЫЙ МЕДИЦИНСКИЙ УНИВЕРСИТЕТ Г. СЕМЕЙ
КАФЕДРА НЕВРОЛОГИИ, ПСИХИАТРИИ И НАРКОЛОГИИ
ДИСЦИПЛИНА: ПСИХИАТРИЯ
Выполнил: Керемханұлы Нұрлыбек,
603 интерн-терапевт
Проверила: Сарсембина Ж. Д.

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4. Вялотекущая шизофрения в общемедицинской практике

А.Б.Смулевич
НЦПЗ РАМН, Москва
На первом этапе комбинированной психофармакотерапии используются
антидепрессанты второго и последующих поколений (серотонинергические
препараты, включая флуоксетин-прозак, циталопрам-ципрамил, тианептинкоаксил и атидепрессанты "двойного" действия: миртазапин-ремерон,
милнаципран-иксел) в сочетании с атипичными нейролептиками и
транквилизаторами. При выявлении признаков резистентности переходят к
второму этапу терапии, предусматривающему введение трициклических
антидепрессантов (ТЦА) в комбинации с традиционными антипсихотиками.
Лечение наиболее устойчивых к терапии ипохондрических состояний,
требующих применения интенсивных методик (третий этап), проводится в
специализированных условиях и предполагает внутривенное капельное введение
ТЦА в сочетании с нейролептиками (галоперидол, сульпирид) или
транквилизаторами (диазепам)ранквилизаторами (диазепам)

5. Кардиологические аспекты проблемы переносимости и безопасности нейролептика М.Ю.Дробижев Клиника кардиологии ММА им. И.М.

М.Ю.Дробижев
Клиника кардиологии ММА им. И.М. Сеченова, НЦПЗ РАМН, Москва
Опасность развития желудочковых нарушений ритма резко возрастает при одновременном применении двух
нейролептиков (в частности, тиоридазина и других фенотиазинов, тиоридазина и пимозида, пимозида и других
фенотиазинов, а также прометазина и других антипсихотиков). Сочетание прометазина с сульпиридом или
левомепромазином может приводить к желудочковой тахикардии и пируэтной тахикардии.
Некоторые нейролептики, в частности трифлуоперазин, могут усиливать позднюю кардиотоксичность
цитостатика доксорубицина. При этом возможно развитие токсического миокардита.
Наконец, некоторые результаты интеракции нейролептиков с другими препаратами отличаются по своим
проявлениям от описанных побочных эффектов антипсихотиков в отношении сердечно-сосудистой системы. В
частности, галоперидол и хлорпромазин, особенно при их назначении в высоких дозах, могут
противодействовать гипотензивному эффекту b-адреноблокаторов. Сочетание производных фенотиазина с
симпатомиметиками сопровождается противодействием вазопрессорному действию этих кардиотропных
препаратов. Совместное назначение кветиапина и варфарина может усиливать антигоагулянтное действие
последнего.
Комбинированная терапия нейролептиками и вступающими с ними во взаимодействие медикаментозными
средствами требует (если вообще допустима) тщательного наблюдения за концентрациями препаратов в
плазме крови и побочными эффектами. Очевидно, что выполнение этого требования сопряжено со
значительными временными и материальными затратами. Соответственно в обычной лечебной практике
следует избегать перечисленных сочетаний.

6. Комбинированное использование антидепрессантов и нейролептиков при аффективных расстройствах и шизофрении: показания к

М.П.Андрусенко, М.А.Морозова
Лаборатория психофармакологии НЦПЗ РАМН, Москва
Назначение комбинированной терапии АД и НЛ в большинстве случаев отражает
симптоматический подход: наличие в клинической картине депрессивных и психотических
симптомов рассматривается как достаточное показание к ее использованию. Этот подход, как
правило, является наиболее характерным в повседневной врачебной практике. Однако
результаты целенаправленных иссследований с контрольными группами показывают
чрезмерную упрощенность такого подхода. Судя по данным исследований, наиболее важную
роль играет не собственно наличие депрессивных и психотических симптомов в клинической
картине, а характер их взаимоотношений внутри синдрома. Так, при развитии депрессивнобредовых состояний в рамках аффективного расстройства комбинированное лечение АД и НЛ
является высокоэффективным. Напротив, при лечении острых состояний, определяющихся
психотическими расстройствами с элементами депрессивных нарушений, развивающихся в
рамках шизофрении и шизоаффективного расстройства, эффективной является монотерапия
НЛ, а добавление АД может вести к ухудшению состояния больных. Тем не менее и в рамках
шизофрении, возможно, существуют состояния, при которых АД показаны. На это указывают
некоторые данные об эффективности добавления АД к НЛ при постпсихотических депрессиях.
Уточнение показаний к комбинированному назначению АД и НЛ требует дальнейших
клинических и клинико-фармакологических исследований.

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8. Drug interactions of psychotropic drugs Sawada Y, Satoh H. Laboratory of Drug Informatics, Graduate School of Pharmaceutical

Sawada Y,Satoh H.
Laboratory ofDrugInformatics, Graduate School of Pharmaceutical Sciences, The University of
Tokyo.
For the appropriate use of psychotropic drugs, such as hypnotics, antidepressants and
antipsychotics, knowledge of the pharmacokinetic characteristics and the interactions of
these drugs are required. The mechanisms of drug interaction can be subdivided into
pharmacokinetic interactions and pharmacodynamic interactions. Among the
former, interactions involving inhibition or induction of cytochrome P450 (CYP)
enzymes are clinically very important. If such interactions cause an increase of systemic
exposure to psychotropic drugs, adverse effects are likely, while a decrease exposure
may lead to treatment failure. In this article, we review drug interactions of
psychotropic drugs from the viewpoints of clinical evidence, mechanism, and
management.

9. Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis Gillies D, Beck A, McCloud A, Rathbone J

Gillies D, Beck A, McCloud A, Rathbone J
In this review we estimated the effects of benzodiazepines (e.g. diazepam, lorazapam, midazolam,
clonazepam), for controlling acutely disturbed behaviour and psychotic symptoms when
compared with placebo, antipsychotic drugs such as haloperidol, or a combination of both
antipsychotics and benzodiazepines. We concluded from this review that there is little difference
between benzodiazepines and antipsychotics for the management of acute psychotic behaviour,
and that the few small trials we found were often poorly reported. The lower incidence of
distressing acute movement disorder in people receiving benzodiazepines may encourage use of
benzodiazepines in preference to the older antipsychotics (administered without additional antimovement-disorder medication), but these adverse effects can be prevented with the use of
alternative drugs such as procyclidine and promethazine. However, all the studies included in this
review were underpowered and failed to identify potentially serious adverse effects of
benzodiazepines such as respiratory depression. This review highlights the need for further more
comprehensive studies in this area.

10. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia Cipriani A, Boso M, Barbui C

Cipriani A, Boso M, Barbui C
When people on clozapine plus risperidone were compared to those on clozapine plus sulpiride,
more people taking risperidone showed an improvement generally. However, when specific
symptoms of schizophrenia were studied, there was change for the better in all groups but no
second antipsychotic was significantly better than the one it was compared to. When looking at
adverse effects, people taking sulpiride were slightly more likely to suffer from hypersalivation
and weight gain than those taking risperidone.

11. Trifluoperazine, an Antipsychotic Agent, Inhibits Cancer Stem Cell Growth and Overcomes Drug Resistance of Lung Cancer Yeh

Yeh CT,Wu AT,Chang PM,Chen KY,Yang CN,Yang SC,Ho CC,Chen CC,Kuo YL,Lee PY,Liu YW,Yen CC,Hsiao
M,Lu PJ,Lai JM,Wang LS,Wu CH,Chiou JF,Yang PC,Huang CY.
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
Using in silico drug screening via Connectivity Map followed by empirical validations, we
repurposed an existing phenothiazine-like anti-psychotic drug, trifluoperazine, as a potential
anti-CSC agent that could overcome EGFR-TKI and chemotherapy resistance.

12. Double-blind placebo-controlled randomized efficacy and safety trial of add-on treatment of dimebon plus risperidone in

Morozova MA,Beniashvili AG,Lepilkina TA,Rupchev GE.
Laboratory of psychopharmacology, Mental Health Research Center of Russian Academy of Medical Sciences, Kashirskoe Shosse
34, 115522 Moscow, Russia. [email protected]
56 male subjects with paranoid schizophrenia were included in the study. All the patients
demonstrated therapeutic response to risperidone as treatment of the acute psychotic episode. After
4 weeks of stability patients were randomized into two groups with placebo or dimebon add-on
treatment in a 1 to 1 ratio for 8 weeks. PANSS, CGI-S, CSDS and NSA-16 were used as clinical
measures of symptom severity. Different aspects of memory, psycho-motor coordination and
executive functioning were assessed with a battery of cognitive tests. Clinical and cognitive
assessment was performed twice: after a patient was randomized and 2 months later.

13. Combination treatment of depression Høiseth G, Solberg DK, Refsum H. Senter for psykofarmakologi, Diakonhjemmet Sykehus,

Høiseth G, Solberg DK, Refsum H.
Senter for psykofarmakologi, Diakonhjemmet Sykehus, Norway.
[email protected]
Severe depression is a common diagnosis and a number of studies have demonstrated the
superiority of antidepressants to placebos. More than half of the patients remain depressed despite
initial treatment. If reasons like incorrect diagnosis and non-optimal choice of drug or doses are
excluded,combination therapy may be considered. Augmentation of antidepressants with lithium or
the thyroid hormone T3 has documented effectiveness, mainly with tricyclic antidepressants, but is
not frequently used. Less documentation exists for a combination of two antidepressant drugs, but
their use is relatively common.

14.

15. Multiple Versus Single Antipsychotic Agents for Hospitalized Psychiatric Patients: Case-Control Study of Risks Versus Benefits

Franca Centorrino, M.D.; Jessica L. Goren, Pharm.D.; John Hennen,
Ph.D.; Paola Salvatore, M.D.; James P. Kelleher, M.D.; Ross J.
Baldessarini, M.D.
Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex,
diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global
Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent
daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical
ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge.Initial doses were
closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for
those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5
days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were
similar (within 11%) for both treatments.

16. Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series

Lerner V, Chudakova B, Kravets S, Polyakova I.
Division of Psychiatry, Ministry of Health Mental Health Center, Faculty of Health Sciences, BenGurion University of the Negev, Beer-Sheva, Israel.
Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended.
However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of
antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been
published about the successful use of clozapine and risperidone in combination for the treatment of
patients with resistant schizophrenic and schizoaffective disorders. However, safety of this
drug combination is open to discussion. This report presents the results of a preliminary study of five
patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The
results suggest that this combinationmay be useful. In the future, the efficacy of risperidoneolanzapine combination should be confirmed in larger study populations before its clinical application is
considered.

17. Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A

Ren-Rong Wu; Jing-Ping Zhao; Xiao-Feng Guo; Yi-Qun He; Mao-Sheng Fang;
Wen-Bin Guo; Jin-Dong Chen; Le-Hua Li
Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15
mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This
investigation was conducted in a double-blind fashion. Planned assessments included body weight, body
mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance
index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the
Assessment of Negative Symptoms (SANS). Results: Of the 40 patients who were randomly assigned, 37
(92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio
levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group
during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus
placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance
index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in
the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased
their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There
was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no
between-group differences. Metformin was tolerated well by all patients.

18. Randomized, Double-Blind, Placebo-Controlled Study of Paliperidone Extended-Release and Quetiapine in Inpatients With Recently

Carla M. Canuso; Bryan Dirks; Jennifer Carothers; Colette Kosik-Gonzalez;
Cynthia A. Bossie; Young Zhu; C. V. Damaraju; Amir H. Kalali; Ramy Mahmoud
In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly
assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week
monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper
end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800
mg/day. The primary endpoint was the difference in mean total change score on the Positive and
Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2week monotherapy phase endpoint. Six-week completion rates were 77.5% (124/160) with paliperidone
extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean
PANSS total change score was greater with paliperidone extended-release than with quetiapine from
day 5 (–11.4 versus –8.2) through the monotherapy phase endpoint (–23.4 versus –17.1). Only
paliperidone extended-release showed significantly greater PANSS improvement compared with
placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with
paliperidone extended-release compared with quetiapine despite similar use of additive therapy
(predominantly other antipsychotics). Common adverse events with paliperidone extended-release,
quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%,
1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse eventrelated discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extendedrelease, quetiapine, and placebo groups.