Заключение и список литературы


Несмотря на значительный прогресс в понимании механизмов действия антипсихотических средств и появления новых поколений препаратов, необходимо признать, что разработанные в 50-60-е годы прошлого века подходы к терапии шизофрении принципиально не изменились и существенного повышения эффективности лечения этого тяжелого контингента больных не произошло. Во-первых, все известные антипсихотические средства разделяют общий механизм действия, блокируя в той или иной степени второй тип дофаминовых рецепторов; с особенностями воздействия на другие нейрорецепторы в основном связана способность препаратов вызывать те или иные побочные эффекты, а также в большей или меньшей степени воздействовать на различные симптомы заболевания. Во-вторых, не было обнаружено явного преимущества отдельных препаратов как по глобальной эффективности (за исключением клозапина у терапевтически резистентных больных), так и в отношении отдельных групп симптомов (галлюцинаторно-бредовых, кататонических, негативных, когнитивных и др.), противорецидивного эффекта, социальных исходов (Lieberman et al., 2005; Jones et al., 2006; Keefe et al., 2007; Swartz et al., 2007; Leucht et al., 2009; Tandon et al., 2010) или в отношении отдельных групп больных, например, у пациентов с первым психотическим эпизодом (Kahn et al., 2008; Sikich et al., 2008; Davidson et al., 2009). Некоторое преимущество АВП при негативной симптоматике и при когнитивных нарушениях отчасти может быть объяснено влиянием ЭПС, которые часто развиваются при применении АПП. Убедительных данных по воздействию антипсихотиков на первичную негативную (дефицитарную) симптоматику не получено (Kirkpatrick et al., 2006). В-третьих, все антипсихотики значительно различаются между собой по переносимости и спектру вызываемых побочных эффектов. При этом АВП вызывают значительно меньше ЭПС, но чаще приводят к метаболическим нарушениям.

Таким образом, все современные антипсихотические препараты имеют больше сходств, чем различий, примерно одинаково эффективны при глобальной оценке и различаются в основном по вызываемым побочным эффектам. Все антипсихотики имеют существенные ограничения как по эффективности, так и по побочным эффектам (около 70% больных в течение года прекращают прием терапии, после чего у большинства больных следует обострение состояния). АВП отличаются прежде всего лучшей неврологической переносимостью и большей эффективностью в отношении негативной симптоматики (преимущественно вторичной) и когнитивных нарушений, обеспечивая в целом несколько более высокий уровень социальной адаптации. Все новые препараты различаются между собой по соотношению эффективности и переносимости и не являются идеальными. В настоящее время не существует никаких доказательных предпосылок для антипсихотической полипрагмазии, которая в отдельных случаях может быть более эффективной, но представляет собой скорее творческую задачу для врача. Дифференцированный (индивидуализированный) подход к терапии по-прежнему является определяющим в достижении оптимального терапевтического результата; при этом важнейшими критериями остаются клиническая картина, подбор адекватной дозы и тщательный мониторинг состояния больного; а необоснованная смена препарата у стабильного больного увеличивает риск развития обострения.

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Актуальные дискуссионные вопросы диагностики, классификации, нейропатологии, патогенеза и терапии шизофрении

Мосолов С.Н.

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