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Ãåíåðàëèçîâàííîå òðåâîæíîå ðàññòðîéñòâî âåñü-ìà ðàñïðîñòðàíåíî è õàðàêòåðèçóåòñÿ ÷ðåçìåðíû-ìè, ïåðñèñòèðóþùèìè, íåêîíòðîëèðóåìûìè îïàñå-íèÿìè, íåðâîçíîñòüþ èëè òðåâîãîé, ñîïðîâîæäàþ-ùèìèñÿ ñèìïòîìàòèêîé, êîòîðàÿ ìîæåò âêëþ÷àòüñëàáîñòü, ðàçäðàæåííîñòü, âíóòðåííåå íàïðÿæåíèå,áåññîííèöó, ñóõîñòü âî ðòó, ãèïåðãèäðîç è êîãíè-òèâíûå íàðóøåíèÿ (7). Ãåíåðàëèçîâàííîå òðåâîæ-íîå ðàññòðîéñòâî ÷àñòî òàêæå ñî÷åòàåòñÿ ñ äðóãè-ìè ïñèõèàòðè÷åñêèìè äèàãíîçàìè, îñîáåííî äåï-ðåññèåé (20, 29), ïîýòîìó ñåëåêòèâíûå èíãèáèòîðûîáðàòíîãî çàõâàòà ñåðîòîíèíà (ÑÈÎÇÑ) ÿâëÿþòñÿïðåïàðàòàìè âûáîðà (16).

Ýñöèòàëîïðàì ÿâëÿåòñÿ åäèíè÷íûì èçîìåðîìöèòàëîïðàìà è â ïåðâóþ î÷åðåäü îòâå÷àåò çà ôóíê-öèþ èíãèáèðîâàíèÿ îáðàòíîãî çàõâàòà ñåðîòîíèíà(15). Èñõîäÿ èç ñðàâíèòåëüíîãî àíàëèçà èíãèáèðî-âàíèÿ çàõâàòà â ìîíîàìèíåðãè÷åñêèõ ïåðåíîñ÷èêàõ,ýñöèòàëîïðàì ÿâëÿåòñÿ íàèáîëåå ñåëåêòèâíûì èçèìåþùèõñÿ ÑÈÎÇÑ (21). Íåñêîëüêèìè ïëàöåáîêîíòðîëèðóåìûìè èññëåäîâàíèÿìè áûëî ïîêàçàíî,÷òî ýñöèòàëîïðàì ÿâëÿåòñÿ ýôôåêòèâíûì è õîðîøîïåðåíîñèìûì ïðåïàðàòîì ïðè ëå÷åíèè äåïðåññèèâ äîçå 10 ìã/ñóò (3, 28).  ýòîé äîçèðîâêå ýñöèòà-ëîïðàì ïî êðàéíåé ìåðå òàê æå ýôôåêòèâåí, êàêöèòàëîïðàì 40 ìã/ñóò (3). Ýñöèòàëîïðàì îêàçûâà-åò áûñòðûé ýôôåêò ïðè ëå÷åíèè ñèìïòîìîâ òðåâî-ãè â ñòðóêòóðå äåïðåññèè (4), à òàêæå àêòèâåí âðÿäå ñìîäåëèðîâàííûõ íà æèâîòíûõ òðåâîæíûõñîñòîÿíèÿõ (19, 26, 27).

Ïðîãðàììà êëèíè÷åñêîãî èçó÷åíèÿ ýôôåêòèâíî-ñòè è áåçîïàñíîñòè ýñöèòàëîïðàìà â ëå÷åíèè ãåíå-ðàëèçîâàííîãî òðåâîæíîãî ðàññòðîéñòâà âêëþ÷àëàâ ñåáÿ òðè ðàíäîìèçèðîâàííûõ, äâîéíûõ ñëåïûõ,ïëàöåáî-êîíòðîëèðóåìûõ èññëåäîâàíèÿ ñ îäèíàêî-âûì äèçàéíîì, âñå èç êîòîðûõ áûëè ïîçèòèâíûìè(6).  ýòîì îò÷åòå ìû ïðåäñòàâëÿåì îáîáùåííûåäàííûå òðåõ èññëåäîâàíèé ïî ýôôåêòèâíîñòè è áå-

ÓÄÊ 616.89–085

ËÅ×ÅÍÈÅ ÃÅÍÅÐÀËÈÇÎÂÀÍÍÎÃÎ ÒÐÅÂÎÆÍÎÃÎÐÀÑÑÒÐÎÉÑÒÂÀ ÝÑÖÈÒÀËÎÏÐÀÌÎÌ:

ÎÁÎÁÙÅÍÍÛÅ ÐÅÇÓËÜÒÀÒÛ ÄÂÎÉÍÛÕ ÑËÅÏÛÕ,ÏËÀÖÅÁÎ-ÊÎÍÒÐÎËÈÐÓÅÌÛÕ ÈÑÑËÅÄÎÂÀÍÈÉ1

Â. Ê. Ãóäìàí, À. Áîóç, Ê. Âàíã

ÑØÀ

çîïàñíîñòè íà÷àëüíîé äîçû (10ìã/ñóò) è îáùåé ïå-ðåíîñèìîñòè ýñöèòàëîïðàìà ïðè èíòåíñèâíîì ëå-÷åíèè ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàññòðîéñòâà.

Áåçîïàñíîñòü è ýôôåêòèâíîñòü ýñöèòàëîïðàìàïðè ëå÷åíèè ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàñ-ñòðîéñòâà îöåíèâàëàñü òðåìÿ ðàíäîìèçèðîâàííû-ìè, äâîéíûìè ñëåïûìè, ïëàöåáî-êîíòðîëèðóåìû-ìè, ìóëüòèöåíòðîâûìè èññëåäîâàíèÿìè äëèòåëüíî-ñòüþ â 8 íåäåëü. Äèçàéí ýòèõ òðåõ èññëåäîâàíèéîòëè÷àëñÿ òîëüêî ìåòîäèêàìè ñëåïîé òèòðàöèè. Âñåòðè èññëåäîâàíèÿ ïðîâîäèëèñü â ÑØÀ â ïåðèîäìåæäó èþëåì 2000 ãîäà è ôåâðàëåì 2002 ãîäà.

 èññëåäîâàíèå âêëþ÷àëèñü àìáóëàòîðíûå ïàöè-åíòû, ìóæ÷èíû è æåíùèíû â âîçðàñòå îò 18 äî 80ëåò ñ äèàãíîçîì ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàñ-ñòðîéñòâà ïî êðèòåðèÿì DSM-IV è ñóììîé áàëëîâïî øêàëå òðåâîãè Ãàìèëüòîíà (HAMA) (12) ðàâíîéèëè áîëåå 18, ñ ìèíèìàëüíûì çíà÷åíèåì êîìïîíåí-òîâ íàïðÿæåííîñòè è òðåâîãè 2.

Êðèòåðèÿìè èñêëþ÷åíèÿ ÿâëÿëèñü ñóììà áàëëîâáîëüøå 17 ïî øêàëå äåïðåññèè Ãàìèëüòîíà(HAMD) (13) èëè ìåíüøàÿ ñóììà áàëëîâ ïî øêàëåòðåâîãè Covi (18), ÷åì ïî øêàëå äåïðåññèè Ðàñêè-íà (23). Òàêæå èñêëþ÷àëèñü ïàöèåíòû ñ âåäóùèìäèàãíîçîì ïåðâîé îñè, êðîìå ãåíåðàëèçîâàííîãîòðåâîæíîãî ðàññòðîéñòâà, âêëþ÷àÿ áîëüøóþ äåïðåñ-ñèþ, èëè òå, êòî ïîäõîäèëè ïî êðèòåðèÿì DSM-IV,ïðèìåíÿåìûì ê áèïîëÿðíîìó ðàññòðîéñòâó, øèçîô-ðåíèè èëè ëþáîìó ïñèõîòè÷åñêîìó ñîñòîÿíèþ,ÎÊÐ, çàäåðæêå ïñèõè÷åñêîãî ðàçâèòèÿ, èëè ïàöèåí-òû ñ ëþáûì ðàñïðîñòðàíåííûì äèçîíòîãåíåòè÷åñ-êèì ðàññòðîéñòâîì èëè êîãíèòèâíûì ðàññòðîé-ñòâîì. Äàííûå î ïñèõîòè÷åñêîì õàðàêòåðå òå÷åíèÿáîëåçíè èëè î ïñèõîòè÷åñêîì ðàññòðîéñòâå â ïðî-øëîì, çëîóïîòðåáëåíèè èëè çàâèñèìîñòè îò ïñèõî-àêòèâíûõ âåùåñòâ çà ïîñëåäíèå 6 ìåñÿöåâ òàêæåÿâëÿëèñü îñíîâàíèåì äëÿ èñêëþ÷åíèÿ.

Óïîòðåáëåíèå ñëåäóþùèõ ïñèõîòðîïíûõ ïðåïà-ðàòîâ ïîçâîëÿëî ó÷àñòâîâàòü â èññëåäîâàíèè: ïðî-ëîíãèðîâàííûõ íåéðîëåïòèêîâ â òå÷åíèå 6 ìåñÿöåâ;ëþáûõ íåéðîëåïòèêîâ, àíòèäåïðåññàíòîâ èëè àíê-

1 Ðàñøèðåííûé ðåôåðàò ñòàòüè, îïóáëèêîâàííîé â The Journalof Affective Disorders. – 2005. – Vol. 87. – P. 161–167, ïðåäîñ-òàâëåí êîìïàíèåé Ëóíäáåê.

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ñèîëèòèêîâ â òå÷åíèå äâóõ íåäåëü (5 íåäåëü äëÿôëóîêñåòèíà); åæåäíåâíàÿ òåðàïèÿ áåíçîäèàçåïèíà-ìè â òå÷åíèå 1 ìåñÿöà. Ñîïóòñòâóþùàÿ òåðàïèÿëþáûì ïñèõîòðîïíûì ïðåïàðàòîì áûëà çàïðåùå-íà (çà èñêëþ÷åíèåì çîëïèäåìà â êà÷åñòâå ñíîòâîð-íîãî).

 òå÷åíèå íåäåëüíîãî ñëåïîãî ïëàöåáî ïåðèîäàïàöèåíòû, ïðîäîëæàþùèå ïîäõîäèòü ïî êðèòåðè-ÿì âêëþ÷åíèÿ, áûëè ðàíäîìèçèðîâàíû íà 8-ìè íå-äåëüíîå äâîéíîå ñëåïîå ëå÷åíèå ýñöèòàëîïðàìîìèëè ïëàöåáî.  òå÷åíèå ïåðâûõ 4-õ íåäåëü ïàöèåí-òû, ðàíäîìèçèðîâàííûå íà ëå÷åíèå àêòèâíûì ïðå-ïàðàòîì, ïîëó÷àëè ôèêñèðîâàííóþ äîçèðîâêó ýñöè-òàëîïðàìà 10 ìã/ñóò. Åñëè, ïî ìíåíèþ èññëåäîâà-òåëÿ, òåðàïåâòè÷åñêèé îòâåò áûë íåäîñòàòî÷åí ê4-îé íåäåëå èëè ê 6-ìó âèçèòó, äîçèðîâêà ìîãëàáûòü óäâîåíà äî 20 ìã/ñóò. Ïàöèåíòû, íå ñïîñîá-íûå ïåðåíîñèòü òàêóþ äîçó, ìîãëè áûòü âîçâðàùå-íû ê ïðèåìó ñòàðòîâîé äîçû íà îñòàâøååñÿ âðåìÿèññëåäîâàíèÿ. Ïàöèåíòû, íå ïåðåíîñÿùèå 10 ìã/ñóò,áûëè èñêëþ÷åíû èç èññëåäîâàíèÿ.

Îöåíêà ýôôåêòèâíîñòè è áåçîïàñíîñòè ïðîâîäè-ëàñü âî âðåìÿ ñêðèíèíãà, íà ìîìåíò íà÷àëà èññëå-äîâàíèÿ è ïîñëå 1-îé, 2-îé, 4-îé, 6-îé è 8-îé íåäå-ëè äâîéíîé ñëåïîé òåðàïèè èëè íà ìîìåíò îêîí÷à-íèÿ èññëåäîâàíèÿ äëÿ âûáûâøèõ ðàíåå ñðîêà.Îñíîâíûì îöåíèâàåìûì ïîêàçàòåëåì áûëî èçìåíå-íèå ñóììû áàëëîâ ïî øêàëå òðåâîãè Ãàìèëüòîíà(HAMA) ñ ìîìåíòà âêëþ÷åíèÿ äî çàâåðøåíèÿ èñ-ïûòàíèé (8 íåäåëü). Äîïîëíèòåëüíûìè îöåíî÷íû-ìè ïîêàçàòåëÿìè ÿâëÿëèñü øêàëà îáùåãî êëèíè÷åñ-êîãî âïå÷àòëåíèÿ òÿæåñòè (CGI-S) è óëó÷øåíèÿ(CGI-I) (11), ïîäøêàëà ïñèõè÷åñêîé òðåâîãè HAMAè ïîäøêàëà òðåâîãè HAMD, ãîñïèòàëüíàÿ øêàëàòðåâîãè è äåïðåññèè (30) è îïðîñíèê êà÷åñòâà æèç-íè (9).  äîïîëíåíèå ê âûøåîïèñàííîìó, ýôôåêòèâ-íîñòü îöåíèâàëàñü ïðè ïîìîùè ïîäøêàëû ñîìàòè-çèðîâàííîé òðåâîãè HAMA è ïðîïîðöèè ïàöèåíòîâ,ïîäõîäÿùèõ ïî êðèòåðèÿì îòâåòà – 50% óëó÷øåíèåïî ñóììå áàëëîâ øêàëû òðåâîãè Ãàìèëüòîíà èëèñóììà áàëëîâ øêàëû CGI-I 1 èëè 2 (çíà÷èòåëüíîåèëè î÷åíü çíà÷èòåëüíîå óëó÷øåíèå) è ðåìèññèÿ(HAMA≤7).

Îöåíêà áåçîïàñíîñòè âêëþ÷àëà â ñåáÿ ñîìàòè÷åñ-êîå îáñëåäîâàíèå, ëàáîðàòîðíûå àíàëèçû, ÝÊà â12-òè îòâåäåíèÿõ è ìîíèòîðèíã âèòàëüíûõ ïîêàçà-òåëåé. Íåáëàãîïðèÿòíûå ýôôåêòû, ñîîáùåííûåïàöèåíòàìè èëè íàáëþäàåìûå èññëåäîâàòåëÿìè,îòìå÷àëèñü â êàæäîì âèçèòå.

Áåçîïàñíîñòü îöåíèâàëàñü íà âñåé ïîïóëÿöèèïàöèåíòîâ, ïîëó÷èâøèõ õîòÿ áû îäíó äîçó ïðåïà-ðàòà â õîäå äâîéíîãî ñëåïîãî èññëåäîâàíèÿ. Àíà-ëèç ýôôåêòèâíîñòè îñíîâûâàëñÿ íà âñåé ðàíäîìè-çèðîâàííîé ïîïóëÿöèè, âêëþ÷àÿ âñåõ ïàöèåíòîâ,ïîëó÷èâøèõ õîòÿ áû îäíó äîçó ïðåïàðàòà â äâîé-íîì ñëåïîì èññëåäîâàíèè è ïðîøåäøèõ õîòÿ áûîäíó ïðîöåäóðó îöåíêè ïî øêàëå òðåâîãè Ãàìèëü-òîíà (HAMA) ïîñëå èñõîäíîé. Âñå ðàñ÷åòû ýôôåê-òèâíîñòè ïðîâîäèëèñü ïðè ïîìîùè LOCF ìåòîäà,ïîçâîëÿþùåãî ó÷èòûâàòü íåäîñòàþùèå äàííûå.

Äàííûå êàæäîãî îòäåëüíîãî èññëåäîâàíèÿ îáðàáà-òûâàëèñü ïðè ïîìîùè àíàëèçà ìîäåëè êîâàðèàòèâ-íîñòè (ANCOVA) ñ òåðàïèåé è èññëåäîâàòåëüñêèìöåíòðîì â êà÷åñòâå ôàêòîðîâ, à èñõîäíûìè äàííû-ìè – â êà÷åñòâå êîâàðèàíòû. Òàêàÿ æå ANCOVAìîäåëü áûëà ïðèìåíåíà ê îáîáùåííûì äàííûìâñåõ òðåõ èññëåäîâàíèé, ãäå òåðàïèÿ, ïðîòîêîë è èñ-ñëåäîâàòåëüñêèé öåíòð â ðàìêàõ ïðîòîêîëà âûñòó-ïàëè â êà÷åñòâå ôàêòîðîâ, à èñõîäíûå äàííûå êàêêîâàðèàíòû.

Îáå ãðóïïû áûëè êëèíè÷åñêè è äåìîãðàôè÷åñ-êè ñîïîñòàâèìûìè. Êîëè÷åñòâî ìóæ÷èí è æåíùèíáûëî ïðàêòè÷åñêè îäèíàêîâûì, ñðåäíèé âîçðàñò ñî-ñòàâèë 39 ëåò. Èñõîäíûå çíà÷åíèÿ îñíîâíûõ ïàðà-ìåòðîâ óêàçûâàëè íà óìåðåííóþ èëè òÿæåëóþ ñèì-ïòîìàòèêó ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàññòðîé-ñòâà â âûáîðêå. Âûáîðêà, ïî êîòîðîé îöåíèâàëàñüáåçîïàñíîñòü, ñîñòîÿëà èç 427 ïàöèåíòîâ, ïîëó÷àâ-øèõ ïëàöåáî, è 429 ïàöèåíòîâ, ïîëó÷àâøèõ ýñöè-òàëîïðàì. Âûáîðêà äëÿ îöåíêè ýôôåêòèâíîñòè ñî-ñòîÿëà èç 419 ïàöèåíòîâ, ïîëó÷àâøèõ ïëàöåáî, è421 – ýñöèòàëîïðàì.  äâóõ ãðóïïàõ äâîéíóþ ñëå-ïóþ òåðàïèþ â òå÷åíèå 8-ìè íåäåëü ïîëó÷èëè 78%ïàöèåíòîâ. Íàèáîëåå ðàñïðîñòðàíåííîé ïðè÷èíîéïðåæäåâðåìåííîãî âûõîäà èç èññëåäîâàíèÿ áûëàíåâîçìîæíîñòü îòñëåæèâàòü õîä òåðàïèè (6,2%), íå-æåëàòåëüíûå ýôôåêòû (6,0%), îòêàç îò ëå÷åíèÿ(5,3%) è íåäîñòàòî÷íûé òåðàïåâòè÷åñêèé îòâåò(2,5%); äëÿ êàæäîé èç óêàçàííûõ ïðè÷èí ñîîòíîøå-íèÿ áûëè íåñêîëüêî âûøå â ñòîðîíó ãðóïïû ïëà-öåáî, çà èñêëþ÷åíèåì íåæåëàòåëüíûõ ýôôåêòîâ.Ïîêàçàòåëè çàâåðøåííîñòè áûëè ñõîæèìè ó âñåõòðåõ èññëåäîâàíèé.

 êàæäîì èç òðåõ îòäåëüíûõ èññëåäîâàíèé, ïîñðàâíåíèþ ñ ïëàöåáî, ýñöèòàëîïðàì çíà÷èòåëüíîóëó÷øèë ñðåäíèå ïîêàçàòåëè øêàëû HAMA. Êîãäàáûëè îáîáùåíû ðåçóëüòàòû òðåõ èññëåäîâàíèé, òîñðåäíèå èçìåíåíèÿ (LOCF) îò èñõîäíîãî óðîâíÿ ê8-îé íåäåëå ïî øêàëå HAMA ñîñòàâèëè 10,1±0,3äëÿ ýñöèòàëîïðàìà è 7,6±0,3 äëÿ ïëàöåáî (p<0,001;ðèñ. 1). Ýñöèòàëîïðàì ïðèâåë ê ñòàòèñòè÷åñêèçíà÷èìûì óëó÷øåíèÿì ïî ñðàâíåíèþ ñ ïëàöåáî èâ îáåèõ ïîäøêàëàõ HAMA: ïñèõè÷åñêàÿ òðåâîãà(–5,8±0,2 ïðîòèâ –3,9±0,2; p<0,001; ðèñ. 2) è ñîìà-òèçèðîâàííàÿ òðåâîãà (–4,3±0,2 ïðîòèâ –3,7±0,2;ð=0,02). Ê ìîìåíòó îêîí÷àíèÿ èñïûòàíèé ðåñïîí-äåðàìè îêàçàëèñü 47,5% ïàöèåíòîâ, ïîëó÷àâøèõýñöèòàëîïðàì, è 28,6% ïàöèåíòîâ, ïîëó÷àâøèõïëàöåáî, à äàâøèìè ðåìèññèè – 26,4% ïàöèåíòîâ,ïîëó÷àâøèõ ýñöèòàëîïðàì, è 14,1% ïàöèåíòîâ,ïîëó÷àâøèõ ïëàöåáî (ð<0,001). Ïî øêàëå CGI-I êêîíöó èññëåäîâàíèÿ ñîîòíîøåíèå ðåñïîíäåðîâ(LOCF), ïîëó÷àâøèõ ýñöèòàëîïðàì, ñîñòàâèëî 52%,à ïëàöåáî – 37% (p<0,001).

Òåðàïèÿ ýñöèòàëîïðàìîì â äîçå 10 ìã/ñóò áûëàôèêñèðîâàííîé â òå÷åíèå ïåðâûõ 4-õ íåäåëü, ÷òîïîçâîëèëî ñîïîñòàâèòü ôèêñèðîâàííóþ äîçèðîâêóñ ïëàöåáî. Çíà÷èòåëüíîå óëó÷øåíèå ïî øêàëåHAMA (ðèñ. 1) è ïî ïîäøêàëå ïñèõè÷åñêîé òðåâî-ãè HAMA (ðèñ. 2) îòìå÷àëîñü óæå ïîñëå ïåðâîé

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íåäåëè òåðàïèè è ñîõðàíÿëîñü â òå÷åíèå ïîñëåäó-þùèõ âèçèòîâ. Ïî øêàëå CGI-S (ðèñ. 3) ðåçóëüòà-òû ëå÷åíèÿ ýñöèòàëîïðàìîì çíà÷èòåëüíî ïðåâîñõî-äèëè ïîêàçàòåëè ïëàöåáî, íà÷èíàÿ ñî 2-îé íåäåëèè â ïîñëåäóþùèå âèçèòû. Êàê âèäíî íà ðèñóíêàõ1–3, óëó÷øåíèå ó ïàöèåíòîâ, ïðèíèìàâøèõ ýñöèòà-ëîïðàì, ïðîäîëæàëî çíà÷èòåëüíî íàðàñòàòü è â ïå-ðèîä ñâîáîäíîé òèòðàöèè ïðåïàðàòà.

Äëÿ òîãî, ÷òîáû âûÿñíèòü ýôôåêòèâíîñòü ýñöè-òàëîïðàìà â äîçå 10 ìã/ñóò, áûëè ïðîàíàëèçèðîâà-íû êîíå÷íûå äàííûå øêàëû HAMA äëÿ ïàöèåíòîâ,êîòîðûå ïîëó÷àëè îäíó è òó æå äîçèðîâêó â òå÷å-íèå 8 íåäåëü. Äëÿ ýòîé ïîäãðóïïû ñðåäíèå âåëè÷è-íû èçìåíåíèé ê 8-îé íåäåëå (LOCF) ñîñòàâèëè–10,7±8,1 äëÿ ýñöèòàëîïðàìà (N=144) è –8,5±6,9äëÿ ïëàöåáî (N=119; p=0,03).

Ýñöèòàëîïðàì õîðîøî ïåðåíîñèëñÿ. Ñëó÷àè èñ-êëþ÷åíèÿ èç èññëåäîâàíèÿ ïî ïðè÷èíå ïîáî÷íûõýôôåêòîâ áûëè íèçêèìè (8% äëÿ ýñöèòàëîïðàìà è4% äëÿ ïëàöåáî). Òîëüêî 6 âèäîâ ïîáî÷íûõ äåé-ñòâèé íàáëþäàëèñü ñ ÷àñòîòîé âûøå 5% è, êàê ìè-íèìóì, âäâîå ìåíüøå äëÿ ïëàöåáî: òîøíîòà, ðàñ-ñòðîéñòâî ýéÿêóëÿöèè, áåññîííèöà, óòîìëÿåìîñòü,ñíèæåíèå ëèáèäî è àíîðãàçìèÿ.

Èíãèáèòîðû îáðàòíîãî çàõâàòà ñåðîòîíèíà ÷àñ-òî ïðèìåíÿþòñÿ äëÿ ëå÷åíèÿ ãåíåðàëèçîâàííîãîòðåâîæíîãî ðàññòðîéñòâà (1, 16). Ðàçðåøåííûìèïðåïàðàòàìè äëÿ ëå÷åíèÿ ãåíåðàëèçîâàííîãî òðå-âîæíîãî ðàññòðîéñòâà ÿâëÿþòñÿ âåíëàôàêñèí, ïàðî-êñåòèí è ýñöèòàëîïðàì. Òàêæå ÷àñòî èñïîëüçóþò-ñÿ áåíçîäèàçåïèíû; îäíîé èç ðàñïðîñòðàíåííûõñõåì ÿâëÿåòñÿ ïîäêëþ÷åíèå áåíçîäèàçåïèíîâ íàðàííèõ ýòàïàõ, òàê êàê íà÷àëî äåéñòâèÿ ÑÈÎÇÑ èëèáóñïèðîíà îáû÷íî ïðîèñõîäèò íåñêîëüêèìè íåäå-ëÿìè ïîçæå (24, 27). Îäíàêî, áåíçîäèàçåïèíû ñâÿ-çàíû ñ òàêèìè íåæåëàòåëüíûìè ýôôåêòàìè, êàêñåäàöèÿ è íàðóøåíèÿ ìîòîðíîé ôóíêöèè (24, 27) èíå ýôôåêòèâíû â îòíîøåíèè ïñèõè÷åñêèõ ñèìïòî-ìîâ òðåâîãè (4, 14).

Ýñöèòàëîïðàì â äîçå 10 ìã/ñóò îêàçàëñÿ ýôôåê-òèâíûì ïðè ëå÷åíèè äåïðåññèè (28, 3). Áûëè

îáîáùåíû äàííûå äîñòóïíûõ ïëàöåáî-êîíòðîëè-ðóåìûõ èñïûòàíèé â îòíîøåíèè òåðàïèè ýñöèòà-ëîïðàìîì ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàñ-ñòðîéñòâà è ïðîâåäåíà îöåíêà ýôôåêòèâíîñòèäîçû 10 ìã/ñóò. Ýñöèòàëîïðàì ïðèâîäèë ê ñòàòèñ-òè÷åñêè çíà÷èìîìó óëó÷øåíèþ ïî ñðàâíåíèþ ñïëàöåáî â îòíîøåíèè ñèìïòîìàòèêè ãåíåðàëèçî-âàííîãî òðåâîæíîãî ðàññòðîéñòâà íà÷èíàÿ ñ ïåð-âîé íåäåëè ïðèìåíåíèÿ, è ïîëîæèòåëüíûé ýôôåêòïðîäîëæàë íàðàñòàòü íà ïðîòÿæåíèè âñåãî èññëå-äîâàíèÿ. Ïîñêîëüêó äëÿ ïåðâûõ ÷åòûðåõ íåäåëüèññëåäîâàíèÿ äîçèðîâêà ïðåïàðàòà áûëà ôèêñèðî-âàííîé íà óðîâíå 10 ìã/ñóò, ýòè ðåçóëüòàòû ïîä-òâåðæäàþò ýôôåêòèâíîñòü äàííîé äîçèðîâêè äëÿëå÷åíèÿ ãåíåðàëèçîâàííîãî òðåâîæíîãî ðàññòðîé-ñòâà. Ïðè ýòîì, ïðîäîëæàâøååñÿ óëó÷øåíèå ó ïà-öèåíòîâ, êîòîðûì äîçà ýñöèòàëîïðàìà òèòðîâà-ëàñü, ïîêàçûâàåò, ÷òî íåêîòîðûå ïàöèåíòû ìîãóòâûèãðàòü îò ïîâûøåíèÿ äîçû äî 20 ìã/ñóò.

Êðîìå òîãî, ýñöèòàëîïðàì õîðîøî ïåðåíîñèëñÿ.Ïîáî÷íûå äåéñòâèÿ, íàèáîëåå ÷àñòî íàáëþäàåìûå

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Ðèñ. 1. Îáùèé áàëë ïî øêàëå òðåâîãè Ãàìèëüòîíà: ñðåäíèåèçìåíåíèÿ ïî ñðàâíåíèþ ñ èñõîäíûìè çíà÷åíèÿìè ó ïàöèåíòîâñ ãåíåðàëèçîâàííûì òðåâîæíûì ðàññòðîéñòâîì, ëå÷åííûõýñöèòàëîïðàìîì èëè ïëàöåáî

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Ðèñ. 2. Áàëëû ïî ñóáøêàëå ïñèõè÷åñêîé òðåâîãè øêàëû òðå-âîãè Ãàìèëüòîíà: ñðåäíèå èçìåíåíèÿ ïî ñðàâíåíèþ ñ èñõîä-íûìè çíà÷åíèÿìè ó ïàöèåíòîâ ñ ãåíåðàëèçîâàííûì òðåâîæ-íûì ðàññòðîéñòâîì, ëå÷åííûõ ýñöèòàëîïðàìîì èëè ïëàöåáî

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Ðèñ. 3. Áàëëû ïî CGI-S: ñðåäíèå çíà÷åíèÿ ó ïàöèåíòîâ ñ ãå-íåðàëèçîâàííûì òðåâîæíûì ðàññòðîéñòâîì, ëå÷åííûõ ýñöè-òàëîïðàìîì èëè ïëàöåáî. Øêàëà CGI-S èìååò çíà÷åíèÿ îò1 äî 7 (1 ñîîòâåòñòâóåò íîðìå, 7 – íàèáîëüøåé âûðàæåííî-ñòè áîëåçíåííîãî ñîñòîÿíèÿ)

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ó ïàöèåíòîâ ñ ãåíåðàëèçîâàííûì òðåâîæíûì ðàñ-ñòðîéñòâîì, ïîëó÷àâøèõ ýñöèòàëîïðàì, áëèçêè êíàáëþäàâøèìñÿ ó ïàöèåíòîâ ñ áîëüøîé äåïðåññè-åé ïðè ëå÷åíèè ýñöèòàëîïðàìîì (17). Êîëè÷åñòâîâûáûâøèõ èç èññëåäîâàíèÿ âñëåäñòâèå ïîáî÷íûõäåéñòâèé áûëî íåáîëüøèì, êàê è óðîâåíü âñòðå÷à-åìîñòè ïîëîâîé äèñôóíêöèè, ÷òî âèäíî èç ñðàâíå-íèÿ ñ äðóãèìè ÑÈÎÇÑ, ïðèìåíÿåìûìè äëÿ ëå÷åíèÿãåíåðàëèçîâàííîãî òðåâîæíîãî ðàññòðîéñòâà (8, 22). ïðÿìûõ èñïûòàíèÿõ íà ïàöèåíòàõ ñ ãåíåðàëèçî-

âàííûì òðåâîæíûì ðàññòðîéñòâîì ýñöèòàëîïðàì âäîçå 10–20 ìã/ñóò âûèãðûâàåò ó ïàðîêñåòèíà â äîçå20–50 ìã/ñóò (2).

Ýòè äàííûå ãîâîðÿò î âîçìîæíîñòè ïðèìåíåíèÿýñöèòàëîïðàìà äëÿ ëå÷åíèÿ ãåíåðàëèçîâàííîãî òðå-âîæíîãî ðàññòðîéñòâà. Ýñöèòàëîïðàì ïîêàçàë ñåáÿýôôåêòèâíûì âî âñåõ òðåõ ïëàöåáî-êîíòðîëèðóå-ìûõ èñïûòàíèÿõ è äîëæåí áûòü ïðåïàðàòîì ïåðâîéëèíèè äëÿ ëå÷åíèÿ ãåíåðàëèçîâàííîãî òðåâîæíîãîðàññòðîéñòâà.

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TREATMENT OF GENERALIZED ANXIETY DISORDER WITH ESCITALOPRAM: POOLED RESULTSFROM DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

W. K. Goodman, A. Bose, Q. Wang

Background: Escitalopram 10 mg/day is an effective and well-toleratedantidepressant. Three randomized controlled trials recently evaluated thesafety and efficacy of escitalopram in the treatment of generalized anxietydisorder (GAD).

Methods: The trial designs were virtually identical, allowing data tobe pooled across studies. Male and female outpatients, ages 18–80 years,with DSM-IV-defined GAD were randomized to double-blind treatmentwith escitalopram or placebo for 8 weeks. Escitalopram dose was fixedat 10 mg/day for the first 4 weeks, after which increases to 20 mg/daywere permitted. The primary efficacy variable was the mean change frombaseline in total Hamilton Anxiety Scale (HAMA) score.

Results: Approximately 850 patients were randomized to double-blindtreatment. In each individual study, escitalopram was significantly superior to

placebo (p<0.05) as measured by change from baseline in HAMA score. By-visit analyses of data pooled across studies revealed significantly greaterimprovement (p<0.05) in the escitalopram group beginning at week 1 or 2 andcontinuing through week 8 for all primary and secondary efficacy variables.The mean change in HAMA total score from baseline to endpoint also wassignificantly greater for patients maintained at escitalopram 10 mg/day thanfor those receiving placebo. Escitalopram was generally well tolerated.

Limitations: The studies included in this analysis were of short-termduration and excluded patients with significant medical and psychiatriccomorbidities, such as major depressive disorder.

Conclusion: Results from the individual trials and the pooled analysisdemonstrate that escitalopram is effective and well tolerated for thetreatment of GAD.