焦慮和焦慮障礙:B族維生素、藏紅花提取物、益生菌
目 錄
一、概述
二、引言
三、焦慮癥類型
四、危險(xiǎn)因素及相關(guān)條件
五、診斷
六、傳統(tǒng)治療
七、新興的和新穎的治療方法
八、飲食和生活方式干預(yù)
九、中西醫(yī)結(jié)合干預(yù)
十、參考文獻(xiàn)
一、概述
摘要和概述
焦慮癥影響約18%的美國成年人。近29%的成年人在一生中會經(jīng)歷焦慮癥。
焦慮癥是一種多方面的障礙,因此必須加以解決,以實(shí)現(xiàn)癥狀緩解。
L-茶氨酸、藏紅花提取物、檸檬香脂、omega-3多不飽和脂肪酸和鎂等營養(yǎng)素,結(jié)合健康的飲食習(xí)慣和壓力管理技術(shù),可以支持身體的壓力反應(yīng)機(jī)制。
什么是焦慮癥?
焦慮是對壓力的一種正常反應(yīng),它可以起到一個(gè)有用的作用:幫助我們避免出現(xiàn)威脅我們安全感的情況。另一方面,當(dāng)所經(jīng)歷的焦慮程度與特定環(huán)境所造成的威脅不成比例時(shí),焦慮癥就會出現(xiàn)。
焦慮癥有不同的類型,包括廣泛性焦慮癥、恐慌癥、強(qiáng)迫癥、恐怖癥和社交焦慮癥。
焦慮癥是由大腦、身體應(yīng)激反應(yīng)網(wǎng)絡(luò)甚至腸道微生物群之間的復(fù)雜相互作用引起的。
一些自然干預(yù)措施,如L-茶氨酸、某些益生菌、藏紅花提取物和omega-3脂肪酸,可能有助于支持健康的應(yīng)激反應(yīng),并減輕與刺激不相稱的焦慮反應(yīng)。
焦慮癥的危險(xiǎn)因素是什么?
焦慮癥或其他精神疾病的個(gè)人或家族病史
性別——女性患焦慮癥的可能性幾乎是男性的兩倍
慢性壓力
年齡-盡管老年人可能會經(jīng)歷獨(dú)特的焦慮,但大多數(shù)焦慮癥都是在年輕時(shí)發(fā)展起來的
經(jīng)歷創(chuàng)傷或壓力事件
生活方式因素,包括吸煙和飲酒
注意:患有焦慮癥的人有更高的風(fēng)險(xiǎn)出現(xiàn)各種各樣的精神和身體健康問題,包括抑郁或雙相情感障礙、心血管疾病和糖尿病。
焦慮癥的癥狀和體征是什么?
注意力難以集中
易怒
肌肉緊張
睡眠障礙
克服憂慮的困難
不同類型焦慮癥的癥狀可能不同,可能包括驚恐發(fā)作、強(qiáng)迫行為、對社交活動(dòng)的恐懼以及再次經(jīng)歷創(chuàng)傷事件。
焦慮癥的傳統(tǒng)治療方法是什么?
認(rèn)知行為療法:
藥物療法:
o一線抗抑郁藥,包括選擇性5-羥色胺再攝取抑制劑(SSRIs)(如氟西汀[Prozac]和舍曲林[Zoloft])和5-羥色胺-去甲腎上腺素再攝取抑制劑(SNRIs)(如度洛西汀[Cymbalta]和文拉法辛[Effexor])
o二線抗抑郁藥,包括三環(huán)抗抑郁藥(TCAs)(如阿米替林[Elavil]和氯丙咪嗪[Anafranil])和單胺氧化酶抑制劑(MAOIs)(如曲尼環(huán)丙咪嗪[Parnate]和苯乙嗪[Nardil])
o其他抗抑郁藥,包括米氮平(Remeron)、曲扎酮(Desyrel)、維拉唑酮(Viibryd)和沃噻西?。═rintellix)
o苯二氮卓類藥物,如安定、阿普唑侖和氯硝西泮
o丁螺環(huán)酮(BuSpar)
o羥嗪(維他利,阿他雷)
o普瑞巴林(Lyrica),一種抗驚厥藥物,對治療焦慮也很有效
o喹硫平,一種抗精神病藥,對減輕焦慮癥狀也很有效
焦慮癥有哪些新的治療方法?
氯胺酮,一種對焦慮癥也有效的全身麻醉劑
o鼻內(nèi)給藥的氯胺酮衍生物,已被批準(zhǔn)用于難治性抑郁癥
阿戈美拉汀,一種人工合成的褪黑素
催產(chǎn)素
艾提伏辛(Stresam)
神經(jīng)刺激技術(shù)
o重復(fù)經(jīng)顱磁刺激
o迷走神經(jīng)刺激
o經(jīng)顱磁刺激
o腦深部刺激
什么樣的飲食和生活方式改變可能對焦慮癥有益?
足夠睡眠
定期鍛煉
適量攝入咖啡因
放松技巧,包括冥想和基于正念的認(rèn)知療法
吃健康均衡的飲食-地中海飲食已被證明可以減少情緒障礙
什么樣的自然干預(yù)措施有助于焦慮癥?
B族維生素。維生素B是合成神經(jīng)遞質(zhì)的輔助因子。B族維生素水平下降會導(dǎo)致同型半胱氨酸水平升高,而焦慮癥的補(bǔ)充可能有助于降低同型半胱氨酸水平和緩解焦慮。
L-茶氨酸。茶氨酸,綠茶和紅茶中的一種氨基酸,已經(jīng)被證明可以改善壓力引起的焦慮、抑郁、睡眠問題,提高認(rèn)知能力。
鎂。鎂缺乏與焦慮癥有關(guān)。補(bǔ)充營養(yǎng)可能有助于減少焦慮。
Omega-3脂肪酸。omega-3脂肪酸對健康有多種益處;它們已被證明能改善情緒和焦慮癥狀。
檸檬香膏。檸檬香膏可以抑制應(yīng)激激素水平,促進(jìn)神經(jīng)發(fā)生。檸檬香膏和纈草的組合被證明能改善焦慮癥狀。
藏紅花。藏紅花提取物已在多項(xiàng)試驗(yàn)中證明,以減少焦慮,抑郁癥狀,改善心理健康。
益生菌。某些益生菌已被證明能改善與焦慮、壓力和抑郁相關(guān)的行為和癥狀。
其他自然干預(yù)如褪黑素、γ-氨基丁酸(GABA)和N-乙酰半胱氨酸可能有助于改善焦慮癥狀。
二、引言
焦慮是一種正常和必要的情緒,它預(yù)示著潛在的傷害,幫助我們避免出現(xiàn)威脅我們安全的情況。焦慮癥不同于正?;蚣膊∠嚓P(guān)的焦慮,因?yàn)榍榫w反應(yīng)與威脅無關(guān),或與威脅不成比例。1焦慮癥是持久性的;焦慮癥是干擾正常功能的能力;可以表現(xiàn)為廣泛的認(rèn)知、情緒、身體和/或行為癥狀,如恐懼,記憶力減退、心率加快、潮熱、煩躁不安、睡眠障礙等。2,3
北美是世界上焦慮癥患病率最高的地區(qū)。據(jù)估計(jì),18%的美國人患有焦慮癥,近29%的人在一生中的某個(gè)時(shí)候會患有焦慮癥。4不幸的是,焦慮癥常常被醫(yī)生忽視或誤診為身體疾病,6據(jù)估計(jì),大約40%的焦慮癥和類似的疾病得不到治療。7
有幾種類型的焦慮癥。其中包括廣泛性焦慮癥、恐慌癥、恐怖癥、社交焦慮癥、分離焦慮癥和其他不太常見的病癥。3在某些情況下,焦慮是由藥物、酒精或其他物質(zhì)的使用或停用引起或加重的。8
焦慮癥與環(huán)境、遺傳和表觀遺傳因素之間的復(fù)雜相互作用有關(guān)。神經(jīng)信號的某些模式和特定的大腦結(jié)構(gòu)已經(jīng)被確認(rèn)在焦慮反應(yīng)中起作用。據(jù)估計(jì),遺傳變異占焦慮風(fēng)險(xiǎn)的30%到67%,而其余的風(fēng)險(xiǎn)歸因于環(huán)境因素,如創(chuàng)傷性生活事件。1焦慮與壓力密切相關(guān),早期生活壓力和應(yīng)激性生活事件可誘發(fā)焦慮癥的發(fā)展,女性患焦慮癥的可能性大約是男性的兩倍。4,11
患有焦慮癥的人患抑郁癥和藥物濫用的風(fēng)險(xiǎn)增加。1,11事實(shí)上,焦慮和抑郁同時(shí)發(fā)生的頻率非常高,一些專家認(rèn)為焦慮和抑郁混合是一種明顯的障礙。6,12焦慮癥還與一系列其他慢性病相關(guān)聯(lián),包括心血管疾病以及神經(jīng)系統(tǒng)、代謝、內(nèi)分泌、胃腸道、肌肉骨骼系統(tǒng)、自身免疫和呼吸系統(tǒng)疾病。3,13,14由于這些疾病可能導(dǎo)致與焦慮癥狀重疊的癥狀,因此準(zhǔn)確診斷和適當(dāng)治療可能具有挑戰(zhàn)性。6
社會支持、健康的應(yīng)對技能和體力活動(dòng)似乎對焦慮癥有保護(hù)作用,而吸煙、酗酒和吸食大麻、對生活事件的負(fù)面看法以及某些與工作有關(guān)的因素則與風(fēng)險(xiǎn)增加有關(guān),健康的飲食模式和放松練習(xí)有助于減少焦慮。16-18
焦慮癥通常通過藥物治療、心理治療或兩者的結(jié)合來治療。在心理治療方式中,認(rèn)知行為療法最能證明療效。1,6盡管藥物治療在許多情況下是有效的,但它們對大約三分之一的患者是不成功的。這可能是由于無法忍受的副作用或缺乏療效造成的。19也許更令人不安的是,該領(lǐng)域的專家們?nèi)栽跔幷?,普通處方藥是否?yōu)于安慰劑。20對于廣泛性焦慮癥和驚恐障礙,研究發(fā)現(xiàn),藥物在較溫和的情況下效果較差。21幸運(yùn)的是,許多中西醫(yī)結(jié)合干預(yù)措施已被發(fā)現(xiàn)可減少焦慮和改善情緒,包括omega-3脂肪酸、B族維生素、益生菌和L-茶氨酸,以及薰衣草、西番蓮、卡瓦、藏紅花和檸檬香脂等草藥制劑。22,23
在這個(gè)方案中,你將了解焦慮的根本原因,焦慮如何影響身體,以及壓力、抑郁和焦慮之間的聯(lián)系。您還將學(xué)習(xí)如何診斷特定的焦慮癥,以及跨越常規(guī)、調(diào)查和綜合療法的治療方法。
三、焦慮癥的類型
自17世紀(jì)末現(xiàn)代精神病學(xué)誕生以來,人們就對焦慮現(xiàn)象進(jìn)行了描述。24今天,美國精神病學(xué)協(xié)會出版的《精神障礙診斷與統(tǒng)計(jì)手冊》(DSM-5)第5版對焦慮障礙進(jìn)行了定義。包括廣泛性焦慮癥、驚恐癥、廣場恐怖癥和其他恐怖癥,以及社交焦慮癥,以及主要影響兒童的分離焦慮癥和選擇性緘默癥。雖然這些是不同的疾病,但它們有重疊的癥狀,經(jīng)常同時(shí)發(fā)生。1
社交焦慮癥
社交焦慮癥(也稱為社交恐懼癥)的特征是在社交場合中由于害怕被審視、尷尬或拒絕而持續(xù)和過度的恐懼或焦慮。1,25,26除了過度的恐懼或焦慮外,社交焦慮的癥狀還可能包括臉紅、手顫抖、惡心或尿急。1焦慮與實(shí)際情況不相符,會導(dǎo)致嚴(yán)重的困擾和長期的功能障礙,從而影響生活領(lǐng)域,如人際關(guān)系,工作和學(xué)校。25社會焦慮癥通常在青春期出現(xiàn),并且可以持續(xù)到成年而無需治療。 它是最常見的焦慮癥類型,一生中某個(gè)時(shí)候會影響多達(dá)15%的人。25,26據(jù)估計(jì),多達(dá)90%的社交焦慮癥患者會出現(xiàn)其他心理健康問題,例如重癥 抑郁癥,飲酒障礙和其他焦慮癥。 社交焦慮癥患者中存在其他精神疾病與更嚴(yán)重的癥狀,更低的治療反應(yīng)可能性,更多的功能障礙和更高的自殺風(fēng)險(xiǎn)相關(guān),這使得識別和治療這種疾病變得更加重要。25
恐懼癥
恐懼癥的定義是由特定的物體或情況引發(fā)的強(qiáng)烈恐懼或焦慮。1據(jù)估計(jì),7.4%的人在一生中經(jīng)歷過恐怖癥障礙。27恐怖癥患者所經(jīng)歷的恐懼或焦慮與恐怖癥所造成的威脅不成比例,導(dǎo)致慢性痛苦和功能受損。27,28恐懼癥的例子包括27:
昆蟲、蜘蛛或蛇等動(dòng)物
自然情況,如高空或雷雨
血液、針頭或醫(yī)療程序
其他情況,如飛機(jī)、電梯或封閉空間
廣泛性焦慮癥
據(jù)估計(jì),美國成年人中有5.7%會在一生中的某個(gè)時(shí)候患上廣泛性焦慮癥,但它往往得不到診斷和治療。29,30患有廣泛性焦慮癥的人會對日常生活產(chǎn)生過度的憂慮或擔(dān)憂。雖然很多人會時(shí)不時(shí)地體驗(yàn)到廣泛性焦慮,但當(dāng)這種焦慮出現(xiàn)在超過六個(gè)月的時(shí)間里,難以控制,導(dǎo)致痛苦和功能困難,并伴有煩躁、疲勞等癥狀時(shí),就會被診斷為廣泛性焦慮癥,注意力不集中,肌肉緊張,睡眠障礙。5,31
驚恐障礙
驚恐障礙的特點(diǎn)是反復(fù)出現(xiàn)意外的驚恐發(fā)作。驚恐發(fā)作是指突然出現(xiàn)的劇烈恐懼或不適,沒有明確的觸發(fā)因素,持續(xù)數(shù)分鐘或更長時(shí)間。5,28身體癥狀,如心悸、出汗、顫抖、呼吸短促、胸痛、惡心、頭暈、窒息、發(fā)冷、麻木或刺痛,驚恐發(fā)作時(shí)伴隨著恐懼感。32心理癥狀,包括自我超脫感、發(fā)瘋恐懼和死亡恐懼也會出現(xiàn)。1,5
分離焦慮與選擇性緘默癥
分離焦慮和選擇性緘默癥是主要影響兒童的焦慮障礙,但也可能發(fā)生在或持續(xù)到成年期。1,33,34分離焦慮癥患者由于無法控制的恐懼或擔(dān)心分離時(shí)會遭遇逆境,對與所依附的人分離產(chǎn)生持續(xù)強(qiáng)烈的焦慮。選擇性緘默癥是一種罕見的焦慮癥,盡管有正常的語言技能,但在某些情況下仍不能說話。選擇性緘默癥通常發(fā)生在5歲前,常與其他焦慮癥有關(guān)。28
其他焦慮癥
還有其他特定和未指定類型的焦慮癥不屬于上述類別。其中包括:
廣場恐懼癥。廣場恐懼癥是一種恐懼癥,表現(xiàn)為明顯的恐懼和回避的情況或者是某個(gè)人在一個(gè)地方可能會陷入困境,無法逃脫,或是在這個(gè)地方無法得到幫助,或者感到尷尬。它通常發(fā)生在另一種類型的焦慮癥的人身上,特別是恐慌癥的人。廣場恐怖癥患者可能會避免使用公共交通工具,避免在開放空間、封閉空間或人群中,避免排隊(duì)或獨(dú)自離家。在嚴(yán)重的情況下,廣場恐懼癥患者會被困在家里。3,28
疾病焦慮癥。疾病焦慮癥于2013年首次被定義為涵蓋一部分先前被診斷為疑病的患者。它的特點(diǎn)是過分擔(dān)心患上或發(fā)展成一種嚴(yán)重的疾病,盡管體檢和實(shí)驗(yàn)室檢查結(jié)果正常,但這種疾病并沒有得到緩解。對疾病的恐懼是持久和慢性的,表現(xiàn)為過度關(guān)注正常的身體感覺,或者頻繁尋求保健或避免保健,并造成極度痛苦和損害日常生活。35
老年人的焦慮
焦慮癥在晚年很常見,但往往得不到承認(rèn)和治療。它們經(jīng)常與抑郁癥、睡眠障礙和藥物使用障礙一起發(fā)生,并可能加速老年人認(rèn)知能力的下降,增加老年癡呆癥、疾病和死亡的風(fēng)險(xiǎn)。最常見的晚年焦慮癥是廣泛性焦慮癥,約占老年人的7%,而廣場恐怖癥估計(jì)約占老年人的5%。大約4%的老年人患有驚恐障礙。36,37
據(jù)報(bào)道,21%到85%的老年人害怕跌倒,這是這個(gè)年齡組特有的一種恐懼癥。跌倒的風(fēng)險(xiǎn)隨著年齡的增長而增加,某種程度的擔(dān)憂是意料之中的;然而,那些對跌倒有恐懼的人有一種強(qiáng)烈的、消耗性的恐懼,這種恐懼與風(fēng)險(xiǎn)不成比例,干擾了日常生活。雖然過去跌倒被認(rèn)為是一個(gè)危險(xiǎn)因素,但對跌倒的恐懼在從未跌倒的人中也很普遍,可能是認(rèn)知功能下降的標(biāo)志。8,38一項(xiàng)試驗(yàn)的結(jié)果表明,采用心理療法、運(yùn)動(dòng)療法和家庭安全評估的治療干預(yù)有助于減少受跌倒恐懼影響的老年人的恐懼和回避行為。39
老年人常見的各種疾病可能被誤認(rèn)為是焦慮癥。這些包括神經(jīng)、心血管、胃腸、內(nèi)分泌或代謝紊亂,以及維生素B缺乏狀態(tài)。重要的是,在診斷出焦慮癥之前要排除這些因素。對于可能引起焦慮的藥物也是如此,必須有一個(gè)完整的用藥史。盡管治療決定會因許多因素而有所不同,但一個(gè)有用的經(jīng)驗(yàn)法則是首選非藥理學(xué)方法作為第一種方法。這些可以包括改變生活方式、行為和認(rèn)知療法、正念練習(xí)和其他類型的基于活動(dòng)的干預(yù)。使用藥物時(shí),選擇性5-羥色胺再攝取抑制劑(SSRIs)通常是一線治療,而苯二氮卓類藥物則是避免使用或短期使用,因?yàn)樗鼈內(nèi)菀自诶夏耆巳褐幸鸩涣挤磻?yīng)。37,40
四、危險(xiǎn)因素和其他相關(guān)條件
焦慮癥的風(fēng)險(xiǎn)與遺傳和環(huán)境因素有關(guān)。45焦慮癥家族史是一個(gè)重要的決定因素,因?yàn)榻箲]癥父母的子女患焦慮癥的可能性顯著增加。42女性患焦慮癥的可能性幾乎是男性的兩倍。4,7此外,兒童時(shí)期的羞怯、早期或成年期的不利或壓力事件、焦慮癥或其他精神疾病的家族史都與風(fēng)險(xiǎn)增加有關(guān)。28某些人格特征也與焦慮癥風(fēng)險(xiǎn)有關(guān)。具體來說,那些容易對壓力反應(yīng)不佳、將普通情況解釋為具有威脅性、將小挫折理解為壓倒性的特質(zhì)與焦慮有關(guān)。1,47
盡管老年人經(jīng)歷了獨(dú)特類型的焦慮,但大多數(shù)焦慮障礙始于兒童期、青少年期和青年期。2分離焦慮和恐懼癥通常出現(xiàn)在兒童期,社交焦慮更常出現(xiàn)在青少年期或青年期;對于恐慌癥和廣泛性焦慮癥,發(fā)病年齡通常在21歲到35歲之間。44
某些生活方式因素已被證明影響焦慮癥的風(fēng)險(xiǎn)。吸煙尤其與焦慮癥風(fēng)險(xiǎn)的增加密切相關(guān)。據(jù)報(bào)道,飲酒也與易患焦慮癥有關(guān)。另一方面,強(qiáng)大的社會關(guān)系、積極的應(yīng)對技能和體育活動(dòng)似乎可以預(yù)防焦慮癥。15
壓力
早期生活應(yīng)激、慢性應(yīng)激、免疫激活和創(chuàng)傷性腦損傷都與下丘腦-垂體-腎上腺(HPA)軸的失調(diào)有關(guān),并且在以后的生活中易患應(yīng)激相關(guān)疾病。45 HPA軸和被稱為杏仁核的大腦區(qū)域之間的交流起著主要作用,表現(xiàn)出焦慮作為一種精神障礙對壓力的反應(yīng)。46杏仁核參與情緒處理和解釋與情緒相關(guān)的刺激。應(yīng)激可改變杏仁核的結(jié)構(gòu)和功能,46-48杏仁核神經(jīng)元信號過活躍是主要焦慮癥的一個(gè)一致特征。47
多種神經(jīng)遞質(zhì)和激素,包括幾個(gè)“神經(jīng)激素”,履行這兩個(gè)角色,涉及到壓力,焦慮和杏仁核之間的相互作用。這些藥物包括去甲腎上腺素、促腎上腺皮質(zhì)激素釋放因子、5-羥色胺、多巴胺、γ-氨基丁酸(GABA)、糖皮質(zhì)激素等。應(yīng)激反應(yīng)迅速激活HPA軸,部分是通過釋放這些神經(jīng)激素,然后激活杏仁核和促進(jìn)焦慮。46,49-51
炎癥的作用
慢性低水平炎癥可能是焦慮癥的驅(qū)動(dòng)因素。在一些焦慮癥患者的研究中,已經(jīng)報(bào)道過炎癥蛋白(如C反應(yīng)蛋白和一些細(xì)胞因子)水平過高,炎癥可能有助于維持焦慮相關(guān)癥狀。58-60
研究表明,炎性細(xì)胞因子影響與恐懼和焦慮相關(guān)的大腦結(jié)構(gòu)(如杏仁核)的信號傳導(dǎo)。58,59,61有人認(rèn)為,炎癥在機(jī)體對感染和損傷等急性攻擊的反應(yīng)中的作用也可能延伸到心理應(yīng)激源,因此,壓力可能會促進(jìn)炎癥反應(yīng)。59應(yīng)激經(jīng)歷和創(chuàng)傷,包括引發(fā)恐懼和焦慮的事件,會增加HPA軸的反應(yīng)性,并促進(jìn)促炎細(xì)胞因子的釋放。52當(dāng)這些應(yīng)激源變?yōu)槁詴r(shí),HPA軸和免疫系統(tǒng)可能會失調(diào)。這是炎癥、慢性疾?。ㄈ缧难芎痛x疾?。┮约扒榫w和焦慮障礙之間聯(lián)系的一種可能機(jī)制。59
焦慮與腸道微生物群
腸道微生物越來越被認(rèn)為是調(diào)節(jié)社會行為、情緒和疼痛敏感性的重要角色,可能通過影響杏仁核功能來實(shí)現(xiàn)。62,63來自臨床前和臨床研究的證據(jù)表明,腸道細(xì)菌產(chǎn)生神經(jīng)遞質(zhì)、激素,以及其他影響大腦功能的炎癥調(diào)節(jié)化合物,有助于應(yīng)激反應(yīng)以及精神和認(rèn)知障礙的風(fēng)險(xiǎn)。64,65腸道微生物組與大腦之間的相互作用可能是慢性胃腸道疾病與焦慮和抑郁癥狀之間聯(lián)系的基礎(chǔ)。64,66因?yàn)樵诰窠】捣矫?,使用飲食、益生菌和益生元補(bǔ)充劑來支持腸道內(nèi)健康的微生物平衡對焦慮癥患者可能有好處。67,68
女性荷爾蒙與焦慮
焦慮癥對女性的影響大約是男性的兩倍。69女性在青春期、經(jīng)期前、懷孕和接近絕經(jīng)期時(shí)等激素劇烈變化的時(shí)期更容易出現(xiàn)焦慮癥或癥狀惡化。此外,如果婦女接受了摘除卵巢的手術(shù),她們會有更高的長期焦慮風(fēng)險(xiǎn)。70,71雌激素具有神經(jīng)保護(hù)作用,如降低大腦氧化應(yīng)激和炎癥,調(diào)節(jié)神經(jīng)元的過度興奮性,影響神經(jīng)生長因子的產(chǎn)生。72
激素療法已被發(fā)現(xiàn)可以降低接近絕經(jīng)期婦女的焦慮和抑郁癥狀。一項(xiàng)研究發(fā)現(xiàn),與未接受激素治療的接近絕經(jīng)期婦女相比,因摘除卵巢手術(shù)而提前絕經(jīng)的婦女在接受激素治療一個(gè)月后抑郁癥狀較少,在接受激素治療三個(gè)月后焦慮癥狀較少。67另一項(xiàng)試驗(yàn)發(fā)現(xiàn)一種合成類雌激素藥物和生物等效物雌二醇在改善自然絕經(jīng)婦女的焦慮和抑郁方面同樣有效。68其他研究報(bào)道,激素治療對接近絕經(jīng)期婦女情緒的積極作用通過與卡瓦提取物的草藥治療相結(jié)合而增強(qiáng)。75,76
有關(guān)更多信息,請參閱雌性激素恢復(fù)方案。
與焦慮相關(guān)的其他情況
焦慮與一系列心理和身體健康問題相關(guān)。疾病不僅常常導(dǎo)致焦慮,焦慮癥患者更容易出現(xiàn)一系列精神和身體健康問題。14,77其中包括:
精神疾病。任何焦慮癥患者隨著時(shí)間的推移都有發(fā)展為另一種焦慮癥的高風(fēng)險(xiǎn)。1焦慮癥患者也經(jīng)常有抑郁障礙或雙相情感障礙。72與普通人群相比,焦慮癥患者自殺更為常見。79
上癮。研究發(fā)現(xiàn),與沒有這些癥狀的人相比,有物質(zhì)使用障礙、病理性賭博和網(wǎng)絡(luò)成癮的人焦慮更為普遍。4
心血管疾病。焦慮癥狀和障礙經(jīng)常發(fā)生在心臟病患者身上,并被發(fā)現(xiàn)與心血管疾病、中風(fēng)和心臟病發(fā)作風(fēng)險(xiǎn)以及心血管疾病相關(guān)死亡的顯著增加有關(guān)。18-25%的中風(fēng)幸存者出現(xiàn)焦慮癥。4,80-82
癌癥。有癌癥病史的人焦慮的患病率在15%到23%之間,晚期癌癥患者的焦慮患病率更高。4
呼吸系統(tǒng)疾病。焦慮在慢性阻塞性肺疾?。–OPD)患者中比在無COPD患者中更常見,并且與不良預(yù)后相關(guān)。83急性呼吸窘迫綜合征(ARDS)的幸存者焦慮的患病率也增加(見側(cè)欄標(biāo)題為“急性呼吸窘迫綜合征后的焦慮”的方案)。4
糖尿病。糖尿病患者比非糖尿病患者更容易受到焦慮癥的影響。4,77
認(rèn)知功能障礙和神經(jīng)系統(tǒng)疾病。焦慮經(jīng)常發(fā)生在認(rèn)知障礙的老年人以及他們的照顧者中,4并且似乎增加了癡呆癥的風(fēng)險(xiǎn)。84焦慮障礙在帕金森病患者中也更為常見。71
自身免疫性疾病。焦慮癥在類風(fēng)濕性關(guān)節(jié)炎、系統(tǒng)性紅斑狼瘡(SLE)和多發(fā)性硬化癥患者中更為常見。77,85,86
消化疾病。“焦慮的胃”——與壓力或焦慮有關(guān)的消化系統(tǒng)不適是一個(gè)眾所周知的現(xiàn)象。同樣,焦慮癥常與慢性功能性胃腸道疾病相關(guān),如胃食管反流?。℅ERD)、消化不良和腸易激綜合征。87-89研究人員指出,這種關(guān)系可能是雙向的,消化和焦慮障礙相互促進(jìn)。這可能反映了腸道和大腦之間的密切聯(lián)系,主要由腸道微生物組介導(dǎo)。63,87,90腸道和大腦之間的這種密切聯(lián)系被稱為“腸道-大腦軸”,腸道微生物組和腸道相關(guān)神經(jīng)元被稱為“第二大腦”。85
急性呼吸窘迫綜合征后的焦慮
急性呼吸窘迫綜合征(ARDS)是一種以嚴(yán)重的肺損傷、炎癥和低血氧水平為特征的危及生命的疾病。ARDS的幸存者可能會有持久的肺損傷和肺功能下降,整體健康狀況下降,生活質(zhì)量下降。86此外,許多人會經(jīng)歷長期的認(rèn)知和情緒后果,包括焦慮,這進(jìn)一步導(dǎo)致生活質(zhì)量下降。92,93一項(xiàng)針對ARDS幸存者的研究表明,38-44%的人在出院兩年后有焦慮癥,26-33%的人有抑郁癥,許多人在出院五年后仍然受到影響。經(jīng)過一年的隨訪,焦慮和抑郁的發(fā)生率高達(dá)66%,92,94許多ARDS幸存者同時(shí)經(jīng)歷焦慮、抑郁和創(chuàng)傷后應(yīng)激障礙(與焦慮有關(guān)的一種情況)。92,94,95
雖然ARDS與存活者精神問題之間的關(guān)系尚不完全清楚,但長期低氧、應(yīng)激反應(yīng)的激活、炎性細(xì)胞因子的暴露以及鎮(zhèn)靜劑和其他藥物的使用是可能的因素。既往抑郁史被認(rèn)為易患ARDS后精神疾病。87在重癥監(jiān)護(hù)室、使用機(jī)械呼吸機(jī)和鎮(zhèn)靜劑的時(shí)間較長均與持續(xù)性心理影響的風(fēng)險(xiǎn)增加有關(guān)。96,97年齡較小、為女性和疾病嚴(yán)重程度也與更大的可能性有關(guān)ARDS后出現(xiàn)精神健康問題的風(fēng)險(xiǎn)。94,98有趣的是,長期使用皮質(zhì)類固醇治療可降低持續(xù)性精神癥狀的風(fēng)險(xiǎn)。98
2003年,一種被稱為突發(fā)性急性呼吸綜合征(SARS)的致命病毒性呼吸道疾病蔓延到29個(gè)國家,在7個(gè)月內(nèi)影響了8000多人。99急性呼吸窘迫綜合征(ARDS)是SARS的并發(fā)癥之一,也是其致命性的常見原因。在SARS幸存者中,令人震驚的是,64%的人在一年后仍報(bào)告有嚴(yán)重的心理問題。99 17年后,一種類似的病毒出現(xiàn)并導(dǎo)致了COVID-19大流行,伴隨著ARDS病例和死亡人數(shù)的急劇上升。研究人員分析了從全世界40000多個(gè)病例收集到的數(shù)據(jù),報(bào)告說焦慮是COVID-19疾病最常見的精神表現(xiàn),影響了4.6%的患者在患病期間。100焦慮和其他精神健康障礙在患病后可能會持續(xù)存在,特別是在那些存活下來的與COVID-19相關(guān)的患者中并將加重心理健康問題所造成的負(fù)擔(dān),廣泛而無情的心理困擾關(guān)系到社會大流行的威脅和現(xiàn)實(shí)。101,102
五、診斷
診斷焦慮癥包括通過仔細(xì)的病史篩選,排除焦慮癥狀的其他原因,以及使用診斷調(diào)查。
篩選
盡管許多人不時(shí)地報(bào)告說他們在焦慮中掙扎,但那些焦慮癥患者有慢性、過度、不可控制的癥狀,與刺激物不成比例,并因焦慮而經(jīng)歷某種程度的殘疾,4 DSM-5建議醫(yī)生使用以下篩選問題來確定焦慮癥的可能性7:
在過去的兩周里,以下問題對你的困擾有多大?
o感到緊張、焦慮、害怕、擔(dān)心或緊張
o感到恐慌或害怕
o避免讓你焦慮的情況
其他的問題(見表1)已經(jīng)被研究出來,以幫助確定具體的焦慮癥。對于表現(xiàn)出輕微或更嚴(yán)重焦慮癥狀的患者,應(yīng)評估其癥狀的原因和影響,并考慮使用診斷工具。
表1:特定焦慮障礙的篩選問題7
驚恐性障礙你是否有突發(fā)的或出乎意料的強(qiáng)烈恐懼發(fā)作/咒語/攻擊?
(如果是,請繼續(xù))
你有過不止一次這樣的襲擊嗎?
這些攻擊中最嚴(yán)重的部分通常在幾分鐘內(nèi)達(dá)到頂峰嗎?
你有沒有經(jīng)歷過這樣的襲擊,并在接下來的一個(gè)月或更長的時(shí)間里生活在害怕再次襲擊或擔(dān)心襲擊的后果中?
社交焦慮障礙害怕尷尬會讓你避免做事或和別人說話嗎?
你是否避免以自己為關(guān)注焦點(diǎn)的活動(dòng)?
你最害怕的是尷尬還是愚蠢?
廣泛性焦慮癥在過去的四個(gè)星期里,你是否經(jīng)常感到擔(dān)心、緊張或焦慮?
你經(jīng)常緊張,易怒,睡眠困難嗎?
排除其他原因
焦慮是常見的癥狀,可能由多種疾病引起,例如心臟,肺,神經(jīng)系統(tǒng)和精神疾病。 甲狀腺功能亢進(jìn)癥也可能引起焦慮。2,7,13患者的病史,體格檢查和基本的實(shí)驗(yàn)室檢查可以幫助排除引起癥狀的其他醫(yī)學(xué)疾病。 在某些情況下,如果癥狀不正?;蛐枰獙Σ∈罚瑱z查和實(shí)驗(yàn)室的異常結(jié)果進(jìn)行隨訪,則可能需要進(jìn)行更復(fù)雜的診斷測試,包括額外的實(shí)驗(yàn)室工作,腦成像等。3
焦慮也可以由服用或停止某些藥物和物質(zhì)引起。其中包括:
咖啡98
酒精104
可可堿105
安非他明105
非處方減充血?jiǎng)?01
一些抗抑郁藥102
一些心臟病藥物103
類固醇104
支氣管擴(kuò)張劑(用于治療哮喘)110
帕金森病藥物106
左旋甲狀腺素(合成甲狀腺激素,用于治療甲狀腺功能減退癥)107
苯二氮卓113
阿片類止痛藥109
作為對焦慮癥評估的一部分,應(yīng)對使用和停用焦慮誘導(dǎo)藥物和物質(zhì)的完整歷史進(jìn)行回顧。7
診斷調(diào)查
漢密爾頓焦慮量表(HAM-A)是醫(yī)生在確定患者癥狀是否符合焦慮癥診斷標(biāo)準(zhǔn)時(shí)最常用的問卷。貝克焦慮量表(BAI)被廣泛用于焦慮癥狀的自我評估。其他焦慮評定量表已被開發(fā)并驗(yàn)證其檢測焦慮癥的能力。115針對兒童、青少年和老年人的工具也可用。8,116
六、傳統(tǒng)治療
焦慮癥通常通過心理治療、藥物治療或兩者的結(jié)合來治療。28這些方法的療效已在多個(gè)試驗(yàn)中得到證明,并通過薈萃分析得到證實(shí)。117-120此外,心理治療和藥理學(xué)方法都顯示出在治療結(jié)束后長期存在的益處。一項(xiàng)對93項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析發(fā)現(xiàn),接受心理治療的焦慮癥患者在停止治療后經(jīng)歷了長達(dá)兩年的改善。接受藥物治療的患者在治療后兩年內(nèi)表現(xiàn)出相似的持久性。盡管完成認(rèn)知行為治療后情緒改善傾向于增加,但停藥后情緒改善傾向于下降,但差異無統(tǒng)計(jì)學(xué)意義。121然而,藥物治療存在不良副作用的風(fēng)險(xiǎn),在某些情況下可能包括嚴(yán)重的戒斷癥狀。122,123治療的選擇取決于焦慮癥的類型和嚴(yán)重程度,以及患者的特征,如年齡、相關(guān)條件和治療偏好。28
認(rèn)知行為療法
認(rèn)知行為療法是一種心理治療方法,患者通過發(fā)展認(rèn)知和行為策略來改變思維和行為的功能障礙模式。大量臨床試驗(yàn)和薈萃分析表明,認(rèn)知行為療法可以改善廣泛性焦慮癥、恐慌癥、社交焦慮癥以及創(chuàng)傷后應(yīng)激障礙和強(qiáng)迫癥患者的癥狀,所有這些都屬于焦慮相關(guān)障礙的范疇。120認(rèn)知行為療法被廣泛用于治療兒童和青少年的焦慮,并在許多嚴(yán)格的臨床試驗(yàn)中被發(fā)現(xiàn)有效。124-127
一項(xiàng)薈萃分析發(fā)現(xiàn),認(rèn)知行為療法導(dǎo)致51%的焦慮和相關(guān)障礙患者病情緩解。128使用正念(專注意識,無判斷,目前)可能會為一些個(gè)體帶來更大的治療成功。129-131最近的研究發(fā)現(xiàn),認(rèn)知行為治療策略的數(shù)字化交付可能有助于作為對個(gè)體治療的補(bǔ)充。130 2017年的一項(xiàng)薈萃分析發(fā)現(xiàn),在認(rèn)知行為治療的基礎(chǔ)上增加藥物治療幾乎沒有什么附加作用益處。有一些證據(jù)表明,藥物治療對那些對認(rèn)知行為療法沒有反應(yīng)的人更有幫助。132總的來說,心理療法和藥物療法對焦慮癥的療效大致相同,認(rèn)知行為療法在團(tuán)體和個(gè)人環(huán)境中都是有效的。7
抗抑郁藥
抗抑郁藥被廣泛用作治療大多數(shù)焦慮癥的一線藥物,通常被認(rèn)為與心理治療一樣有效。1,2,7然而,一些作者認(rèn)為抗抑郁藥治療焦慮癥的證據(jù)仍然模棱兩可。例如,在廣泛性焦慮癥和驚恐障礙中,那些癥狀輕微的患者從抗抑郁治療中獲益甚微,潛在的危害可能大于益處。21對抗抑郁藥治療驚恐障礙的隨機(jī)對照試驗(yàn)的詳盡回顧得出結(jié)論,抗抑郁藥可能比安慰劑更有效,但證據(jù)不足以堅(jiān)定地建議在臨床實(shí)踐中使用這些藥物。117一些作者發(fā)現(xiàn),與安慰劑、心理治療或鍛煉相比,藥物抗抑郁治療幾乎沒有優(yōu)勢,所有這些治療的不良反應(yīng)風(fēng)險(xiǎn)更低。133,134
一線抗抑郁藥。選擇性5-羥色胺再攝取抑制劑(SSRIs)和5-羥色胺-去甲腎上腺素再攝取抑制劑(SNRIs)是兩類抗抑郁藥,是治療成人焦慮癥的一線藥物。135,136它們的部分作用是通過增加大腦特定區(qū)域的5-羥色胺和去甲腎上腺素(也稱為去甲腎上腺素)的可用性。117度洛西汀(Cymbalta)、文拉法辛(Effexor)、艾司西酞普蘭(Cipralex、Lexapro)、舍曲林(Zoloft)和帕羅西?。≒axil)是這類藥物的例子,推薦用于廣泛性焦慮、恐慌和社交焦慮障礙患者。然而,這些藥物通常需要4-6周才能達(dá)到最佳療效,并且會引起一些人無法忍受的副作用,如體重增加和性功能障礙,以及頭痛、消化不良、失眠或鎮(zhèn)靜。
為了在患者、藥物和劑量之間尋求合適的藥物“匹配”,一個(gè)艱苦的嘗試和錯(cuò)誤的過程并不少見。132此外,停止這些類別的藥物治療通常會導(dǎo)致長期和嚴(yán)重的戒斷綜合征。122最近關(guān)于停止SSRIs和SNRIs相關(guān)的嚴(yán)重和持久性戒斷綜合征的報(bào)告,提出了關(guān)于這些藥物在治療焦慮方面優(yōu)于苯二氮卓類藥物(見下文)的假設(shè)問題。123
二線抗抑郁藥。三環(huán)類抗抑郁藥 (TCAs),如阿米替林(Elavil)、氯丙咪嗪(Anafranil)和多塞平(Silenor),是一類較老的藥物,可以增加突觸中去甲腎上腺素和5-羥色胺的水平(即神經(jīng)遞質(zhì)通過的通訊神經(jīng)元之間的間隙)。TCAs會引起一系列不愉快的副作用,如口干、便秘、視力模糊、鎮(zhèn)靜和體重增加。它們還可引起心律失常,使SSRIs和SNRIs成為治療焦慮和抑郁的首選一線藥物。136,137然而,TCAs可能在治療對其他藥物無反應(yīng)的焦慮癥患者方面發(fā)揮作用。136
單胺氧化酶抑制劑(MAOIs)的使用增加了多巴胺、血清素和去甲腎上腺素的腦突觸水平。MAOIs也是一種較老的藥物,在實(shí)踐中已被具有更好安全性的藥物所取代。然而,在對其他藥物無反應(yīng)的難治性病例中,有時(shí)仍建議使用MAOIs。136,137例如,曲尼環(huán)丙咪嗪(Parnate)和苯乙嗪(Nardil),MAOIs可引起與其他藥物和某些食物的危險(xiǎn)相互作用,并可引起副作用,如疲勞、低血壓、口干,頭痛、失眠、消化系統(tǒng)癥狀、體重增加和性功能障礙。137,138
二線抗焦慮藥物
苯二氮卓類。苯二氮卓類是鎮(zhèn)靜催眠藥,通過增加神經(jīng)遞質(zhì)GABA受體的激活而起作用。這類藥物包括安定、勞拉西泮、阿普唑侖和氯硝西泮。136苯二氮卓類藥物起效快,通常用于短期使用。苯二氮卓類藥物治療焦慮癥的受歡迎程度在過去幾年中有所下降,因?yàn)樗鼈冇锌赡鼙粸E用和上癮。然而,苯二氮卓類藥物或抗抑郁藥物是否應(yīng)該被普遍宣布為治療廣泛性焦慮癥的首選藥物仍然存在爭議,140確定每個(gè)病人的最佳藥物方案需要個(gè)體化的方法。苯二氮卓類藥物可能有助于控制抗抑郁藥開始使用后的前幾周內(nèi)的焦慮,因?yàn)榭挂钟羲幮枰獢?shù)周才能完全發(fā)揮作用。隨著抗抑郁藥開始生效,苯二氮卓類藥物可以逐漸減少。140苯二氮卓類藥物的常見副作用包括嗜睡、疲勞、頭暈、出汗、口干、便秘和躁動(dòng)。136,141
丁螺環(huán)酮。丁螺環(huán)酮(Buspar)是一種抗焦慮藥物,主要用于治療廣泛性焦慮癥。它似乎通過增加5-羥色胺受體的激活而起作用,但也會降低多巴胺的活性。136,142使用丁螺環(huán)酮的患者可能會出現(xiàn)不良副作用,如頭暈、惡心、腹瀉、頭痛、神經(jīng)緊張、失眠、視力模糊、意識模糊、虛弱、震顫、肌肉疼痛、麻木、胸痛和皮疹。此外,丁螺環(huán)酮與停藥后可能持續(xù)的運(yùn)動(dòng)障礙有關(guān)。137
羥嗪。羥嗪(Vistaril,Atarax)是一種抗組胺藥,幾十年來一直被用于治療焦慮相關(guān)疾病。盡管被認(rèn)為對廣泛性焦慮癥比安慰劑更有效,但現(xiàn)有研究的低質(zhì)量不允許將羥嗪作為一線治療。136,143,144羥嗪可引起嗜睡、口干、頭暈和頭痛。144
其他藥物
米氮平(Remeron)、曲唑酮(Desyrel)、維拉唑酮(Viibryd)和伏硫西?。═rintellix)是具有復(fù)雜作用機(jī)制的抗抑郁藥。這些抗抑郁藥沒有足夠的證據(jù)支持其療效,也沒有被美國食品和藥物管理局(FDA)批準(zhǔn)用于治療焦慮癥,因此不是一線療法。一般來說,它們的副作用與SSRIs和SNRIs相似。米氮平(Remeron)和曲氮酮(Desyrel)被認(rèn)為具有鎮(zhèn)靜作用。維拉唑酮(Viibryd)和伏硫西汀(Trintellix)已被批準(zhǔn)用于治療重度抑郁癥,但沒有大量證據(jù)支持其用于焦慮癥。136,137
普瑞巴林(Lyrica)用于治療焦慮癥,主要是廣泛性焦慮癥,并且在結(jié)構(gòu)上與GABA相關(guān)。140在廣泛性焦慮癥患者中,發(fā)現(xiàn)普瑞巴林比SNRI文拉法辛更快地減輕癥狀,并且與苯二氮卓類藥物一樣有效。136,146然而,普瑞巴林的副作用包括體重增加、頭暈、嗜睡、頭痛、口干和視力扭曲。重要的是,普瑞巴林可引起依賴性,并與致命的過量用藥有關(guān),尤其是與其他藥物一起使用時(shí)。136
奎硫平(Seroquel)是一種非典型抗精神病藥物,主要用于治療雙相情感障礙和精神分裂癥等精神疾病。小劑量奎硫平對廣泛性焦慮癥患者的焦慮癥狀有明顯的緩解作用。喹硫平與體重增加和代謝性疾病有關(guān),盡管這些問題在高劑量時(shí)更受關(guān)注??蚱?jīng)]有被FDA批準(zhǔn)用于治療焦慮癥,盡管這種非標(biāo)簽藥物被認(rèn)為是最有效的藥物之一。136,146奧氮平(Zyprexa)和利培酮(Risperdal)是其他非典型抗精神病藥物,有時(shí)用作非標(biāo)簽藥物治療焦慮癥。141
七、新興的新穎的治療策略
許多用于治療焦慮癥的藥物的療效可疑,不良的副作用,或者兩者兼而有之。因此,研究正在進(jìn)行,希望能找到更安全、更有效的治療焦慮癥的藥物。研究中的大多數(shù)新療法都是藥理學(xué)的。神經(jīng)刺激,幾十年來一直被認(rèn)為具有積極的心理作用,是一種很有前途的非藥理學(xué)研究方法。
藥物療法
氯胺酮。氯胺酮(Ketalar)是一種對中樞神經(jīng)系統(tǒng)有廣泛影響的藥物,它抑制大腦中的谷氨酸受體,即N-甲基-D-天冬氨酸(NMDA)受體。雖然氯胺酮已被批準(zhǔn)用作全身麻醉劑,但它在精神障礙,包括藥物使用、抑郁癥和焦慮癥中的作用最近引起了人們的興趣。氯胺酮靜脈給藥,但鼻腔給藥的衍生物(esketamine[Ketanest])已被批準(zhǔn)用于治療頑固性抑郁癥。142
據(jù)報(bào)道,氯胺酮可緩解社交焦慮癥和廣泛性焦慮癥患者的癥狀。148,149一些證據(jù)表明,氯胺酮可引起神經(jīng)元連接性和興奮性的增加。149反復(fù)和長期使用氯胺酮的安全性仍在探討中。不幸的是,由于氯胺酮的迷幻特性,濫用和依賴是令人擔(dān)憂的問題。147-149
阿戈美拉汀。阿戈美拉?。╒aldoxan)是神經(jīng)激素褪黑素的合成版本,在歐洲被批準(zhǔn)用于治療抑郁癥,并顯示出抗焦慮作用。149阿戈美拉汀激活褪黑素途徑,在調(diào)節(jié)晝夜節(jié)律周期和血清素信號傳導(dǎo)、影響睡眠和情緒方面發(fā)揮重要作用,還有可能增強(qiáng)神經(jīng)發(fā)生和神經(jīng)可塑性(形成新神經(jīng)元連接的能力)。144,149三項(xiàng)隨機(jī)對照試驗(yàn)發(fā)現(xiàn)阿戈美拉汀對廣泛性焦慮癥患者有效。這些試驗(yàn)還發(fā)現(xiàn),與SSRIs和SNRIs相比,阿戈美拉汀具有副作用低、更好的臨床反應(yīng)和更快的起效。43,150阿戈美拉汀與大多數(shù)輕度至中度不良反應(yīng)有關(guān),包括頭痛、頭暈、嗜睡、疲勞和消化不良。它的長期安全性還有待探討,但肝毒性的罕見病例已經(jīng)被報(bào)道;然而,阿戈美拉汀似乎比目前許多治療焦慮癥的藥物更安全。42,150
催產(chǎn)素。催產(chǎn)素是一種激素,在大腦中與壓力、恐懼和焦慮有關(guān)的區(qū)域釋放,包括杏仁核,在那里它通過減少神經(jīng)元活動(dòng)來抵消這些狀態(tài)。催產(chǎn)素參與社會行為、情緒、生殖行為和應(yīng)激反應(yīng);低催產(chǎn)素與焦慮增加有關(guān)。149,151催產(chǎn)素用于孕婦誘導(dǎo)子宮收縮。在廣泛性焦慮和社交焦慮障礙患者的初步試驗(yàn)中發(fā)現(xiàn),經(jīng)鼻給予催產(chǎn)素具有快速的抗焦慮作用。催產(chǎn)素治療焦慮癥的證據(jù)是初步的,但它被認(rèn)為是一個(gè)有希望的藥物開發(fā)目標(biāo)。149,151
艾提伏辛。艾提伏辛(Stresam)是一種抗焦慮和抗癲癇的藥物,與苯二氮卓類藥物一樣,通過增加GABA受體的反應(yīng)性,使神經(jīng)系統(tǒng)安靜下來。臨床前研究表明,艾提伏辛還可以減少大腦炎癥,增加促進(jìn)神經(jīng)可塑性因子的產(chǎn)生。初步試驗(yàn)表明,艾提伏辛可以減輕焦慮癥狀,而不影響記憶或警覺性,停藥后也不會引起依賴、戒斷癥狀或反跳焦慮。152,153艾提伏辛是20世紀(jì)60年代開發(fā)的,在許多國家上市,用于治療焦慮癥,但美國仍在調(diào)查這一用途。艾提伏辛可引起不良副作用,包括皮疹、結(jié)腸炎、肝毒性和異常子宮出血。149
迷幻療法
迷幻藥在全世界的宗教、娛樂和醫(yī)學(xué)中有著悠久的應(yīng)用歷史。對其可能的治療應(yīng)用的研究可以追溯到20世紀(jì)40年代和50年代,當(dāng)時(shí)麥角酸二乙胺(LSD)和化學(xué)物質(zhì)psilocybin是著名的藥劑師Albert Hoffer發(fā)現(xiàn)的“神奇”蘑菇的活性成分。154,155這些化合物已上市并提供給研究人員。對他們的神經(jīng)和精神影響的調(diào)查沿著兩條軌跡發(fā)展152:
低劑量治療,加強(qiáng)多療程的心理治療。這種方法被用來治療焦慮癥和其他一些精神疾病。
大劑量治療可引發(fā)一種或幾種轉(zhuǎn)化經(jīng)驗(yàn)。 主要在患有藥物濫用障礙的患者中研究了這種方法。
針對非法制造、娛樂性使用、黑市分銷和悲慘結(jié)局的案例,美國通過了1970年《管制物質(zhì)法》,從而停止了對迷幻劑的研究。然而,人們對迷幻藥的興趣與日俱增,許多設(shè)計(jì)良好的對照試驗(yàn)正在進(jìn)行或已經(jīng)發(fā)表,包括來自馬里蘭州巴爾的摩市約翰霍普金斯大學(xué)的一個(gè)著名研究小組。154-157研究結(jié)果表明,在合格醫(yī)療保健提供者監(jiān)督下,在受控環(huán)境下使用的迷幻藥可能是焦慮和抑郁患者的一種有價(jià)值的治療方式,尤其是癌癥或其他危及生命的疾病患者,或與臨終姑息治療相關(guān)的患者。154,158
Psilocybin是一種生物堿化合物,與Psilocybe菌群中的蘑菇關(guān)系最為密切,但也存在于其他類型的真菌中。156它通過與血清素受體相互作用來改變感知、思想、意識,152兩項(xiàng)針對晚期癌癥患者的隨機(jī)對照試驗(yàn)發(fā)現(xiàn),單劑量或雙劑量(第一次高劑量治療,五周后再進(jìn)行低劑量治療)的psilocybin與心理治療結(jié)合使用,可顯著、持久地降低焦慮和抑郁。在單劑量試驗(yàn)中,將psilocybin加心理治療與安慰劑加心理治療進(jìn)行比較。這兩項(xiàng)試驗(yàn)的參與者報(bào)告說,平均而言,絕望感減少了,精神幸福感改善了,生活質(zhì)量提高了,而且這些變化在治療后持續(xù)了六個(gè)月以上。160,161在一項(xiàng)針對威脅生命的疾病患者的試驗(yàn)中,LSD輔助的心理治療減少了焦慮,提高了生活質(zhì)量,并在治療12個(gè)月后產(chǎn)生影響情緒健康、習(xí)慣和世界觀的持久益處。162
另一種迷幻劑亞甲二氧基甲基苯丙胺(MDMA,也被稱為搖頭丸),是積極研究的對象,作為治療創(chuàng)傷后應(yīng)激障礙的心理治療的輔助手段。重要的是,在使用這些或其他致幻劑的臨床試驗(yàn)中,經(jīng)過仔細(xì)的篩選、準(zhǔn)備和監(jiān)督,已報(bào)道了有限的嚴(yán)重不良反應(yīng)。164
用迷幻藥治療焦慮癥目前僅限于研究環(huán)境,在任何情況下都不應(yīng)在沒有合格醫(yī)療機(jī)構(gòu)監(jiān)督的情況下嘗試。如果研究繼續(xù)證明這些療法是安全有效的,以迷幻藥為基礎(chǔ)的治療方案可能會變得更加普遍。
大麻與焦慮
大麻(或大麻)是世界上使用最廣泛的精神活性物質(zhì)之一。165隨著推動(dòng)非犯罪化和合法化的力度加大,了解大麻及其主要活性成分四氫大麻酚(THC)和大麻二酚(CBD)如何影響精神健康非常重要。166
大麻成分被稱為大麻素,與人類神經(jīng)系統(tǒng)中的內(nèi)源性大麻素受體相互作用。165內(nèi)源性大麻素是一種內(nèi)源性信號分子,對大腦功能有許多重要影響,包括調(diào)節(jié)食欲、睡眠、記憶、學(xué)習(xí)、動(dòng)機(jī)和痛覺。167,168大麻素受體遍布身體的各個(gè)部位,這表明大麻素的整體效應(yīng)也超出了大腦。166有趣的是,慢性應(yīng)激導(dǎo)致的內(nèi)源性大麻素信號減少,與沿HPA軸的應(yīng)激反應(yīng)性增加和焦慮行為增加有關(guān)。170通過與內(nèi)源性大麻素系統(tǒng)相互作用,大麻素在治療一系列神經(jīng)和精神疾病方面具有很大的治療潛力。165,167,171
單劑量的THC已被證明能誘發(fā)許多急性精神病效應(yīng),如妄想和幻覺、情緒平緩、動(dòng)機(jī)喪失和情緒變化,這些似乎都不受CBD的緩沖。166 THC、CBD及其聯(lián)合應(yīng)用的治療潛力已成為許多臨床前和臨床試驗(yàn)的主題。對臨床試驗(yàn)進(jìn)行的一項(xiàng)大型薈萃分析發(fā)現(xiàn),無論有無CBD,THC都能促進(jìn)其他疾病患者焦慮癥狀的輕微改善,172而CBD本身在治療廣泛性焦慮癥、社交焦慮癥和藥物使用障礙方面有一定的益處。173,174 CBD也被發(fā)現(xiàn)對健康志愿者有抗恐慌作用。172
盡管大麻在治療焦慮癥方面可能有用,但長期過量使用大麻可能會對精神健康造成嚴(yán)重危害,增加焦慮、抑郁和睡眠障礙以及精神病和自殺的風(fēng)險(xiǎn)。然而,應(yīng)該指出的是,某種程度的反向因果關(guān)系可能解釋了這一點(diǎn):有情緒和心理障礙的人可能會轉(zhuǎn)向大麻,希望找到緩解。一項(xiàng)研究發(fā)現(xiàn),在習(xí)慣性過度使用大麻的人中,減少使用大麻會改善焦慮、抑郁和睡眠狀況。176-178
據(jù)報(bào)道,單用CBD會引起輕微的副作用,如疲勞、腹瀉、食欲和體重的變化,但總的來說有良好的副作用;然而,需要進(jìn)一步的研究來了解長期使用CBD的影響。176
神經(jīng)刺激
神經(jīng)刺激技術(shù)已顯示出作為獨(dú)立治療或與其他治療方法聯(lián)合治療焦慮癥的替代方法的前景。180這些治療方法中的一些被認(rèn)為是通過幫助神經(jīng)網(wǎng)絡(luò)的活動(dòng)和功能正?;鹱饔玫模P(guān)于其作用機(jī)制的基本問題尚不清楚未答復(fù)。178
重復(fù)性經(jīng)顱磁刺激是研究最多的一種焦慮神經(jīng)刺激方法,對廣泛性焦慮癥有積極作用。180它包括一個(gè)放在頭皮上的磁線圈,產(chǎn)生磁脈沖來刺激大腦中的神經(jīng)細(xì)胞。179經(jīng)顱直流電刺激是另一種刺激方法神經(jīng)刺激的一種類型,包括通過頭皮上的兩個(gè)電極通過特定的大腦區(qū)域傳遞非常小的電流(1-2毫安)。這種方法已被證明對焦慮癥有效,但其作用機(jī)制尚未完全了解,證據(jù)表明,與藥物和認(rèn)知行為療法結(jié)合使用時(shí)效果最佳。183
另一種抗焦慮的神經(jīng)刺激是迷走神經(jīng)刺激。迷走神經(jīng)在杏仁核和其他參與處理焦慮情緒和生理方面的大腦區(qū)域中有聯(lián)系,據(jù)報(bào)道,電刺激迷走神經(jīng)可減輕驚恐障礙患者和其他具有焦慮成分的患者的焦慮癥狀。184,185這種神經(jīng)刺激包括在左迷走神經(jīng)周圍植入電極,在鎖骨下方植入脈沖發(fā)生器。由于可能的手術(shù)并發(fā)癥,以及睡眠呼吸暫停的風(fēng)險(xiǎn),早發(fā)或晚發(fā)的異常心律(在罕見的情況下可能是嚴(yán)重的),以及其他潛在的不良反應(yīng),迷走神經(jīng)刺激的使用歷來局限于嚴(yán)重和難治性病例。然而,經(jīng)皮電刺激迷走神經(jīng)的新技術(shù)目前正被探索為更安全、微創(chuàng)和更便宜的選擇。184
腦深部刺激包括使用植入大腦的電極將電脈沖直接傳遞到特定的大腦區(qū)域,目前正在研究作為強(qiáng)迫癥和創(chuàng)傷后應(yīng)激障礙患者的一種治療選擇。深部腦刺激被批準(zhǔn)用于多種疾病的治療,包括晚期帕金森病。185,186盡管帕金森病患者的臨床試驗(yàn)結(jié)果有些不一致,但深部腦刺激似乎能在一定程度上改善一些患者的抑郁和焦慮癥狀,一些初步的臨床證據(jù)表明,腦深部刺激能夠緩解各種情緒障礙的焦慮癥狀。190,191
八、飲食和生活方式干預(yù)
飲食
大腦的結(jié)構(gòu)和功能在一定程度上取決于我們飲食中營養(yǎng)素的可獲得性。192飲食成分可以影響影響大腦功能的許多因素,包括神經(jīng)遞質(zhì)合成和信號傳遞、腸道激素的釋放、腸道微生物群的組成和基因表達(dá)模式。飲食因素也調(diào)節(jié)成人神經(jīng)細(xì)胞的形成,神經(jīng)可塑性和腦免疫功能。所有這些因素都與心理健康和焦慮有關(guān)。192-194
富含植物多酚和多不飽和脂肪酸的健康飲食,以及維生素補(bǔ)充劑,可能有助于健康的認(rèn)知、應(yīng)激反應(yīng)、神經(jīng)炎癥和情緒。192,195增加高熱量和加工食品的攝入可能會增加兒童、青少年和成年期患焦慮癥的可能性,動(dòng)物研究發(fā)現(xiàn),反復(fù)接觸含糖豐富的食物會引起焦慮相關(guān)的行為。196,197另一方面,多酚等植物化學(xué)物質(zhì)會促進(jìn)健康的微生物群,進(jìn)而調(diào)節(jié)抑郁和焦慮的神經(jīng)炎癥。198在許多研究中,飲食中富含水果和蔬菜的人,以及人們注意到,與水果和蔬菜攝入量低的人相比,漿果、柑橘和綠葉蔬菜等植物性食物的特定亞組具有更高水平的樂觀主義和自我效能(對實(shí)現(xiàn)目標(biāo)的能力的信心)和更低水平的情緒困擾,包括抑郁癥狀。199然而,在這些研究中,因果關(guān)系的方向很難解釋。
健康的飲食模式與成年人更好的心理健康有關(guān)。200在老年人中,一項(xiàng)研究發(fā)現(xiàn),以高飽和脂肪和糖為特征的飲食模式與更高的焦慮水平有關(guān)。16堅(jiān)持地中海式飲食,強(qiáng)調(diào)水果、蔬菜、全谷類、橄欖油,在一項(xiàng)研究中,堅(jiān)果、種子和豆類與焦慮癥風(fēng)險(xiǎn)降低和總體情緒改善有關(guān)。對這項(xiàng)研究結(jié)果的分析表明,水果和蔬菜是與降低抑郁、焦慮的幾率最密切相關(guān)的飲食成分,201對獨(dú)立生活在老年護(hù)理社區(qū)的老年受試者進(jìn)行的一項(xiàng)公開試驗(yàn)表明,他們更愿意堅(jiān)持為期六個(gè)月的地中海飲食方案,并結(jié)合運(yùn)動(dòng)療法,減少焦慮和抑郁,改善認(rèn)知功能的某些方面。199
在許多研究中,人們注意到,與水果和蔬菜攝入量低的人相比,飲食中富含水果和蔬菜的人,以及漿果、柑橘和綠葉蔬菜等植物性食物的特定亞組,樂觀和自我效能(對自己實(shí)現(xiàn)目標(biāo)的能力有信心)水平較高,情緒困擾水平較低,包括抑郁癥狀。199然而,在這些研究中,因果關(guān)系的方向很難解釋。
在大多數(shù)人中,喝咖啡與積極的情緒、健康的認(rèn)知功能和整體幸福感有關(guān)。200然而,過量的咖啡因可能會增加焦慮和睡眠中斷,尤其是對敏感人群。201因此,在焦慮癥患者中,咖啡因攝入的益處和風(fēng)險(xiǎn)需要在個(gè)體基礎(chǔ)上加以考慮。
研究表明,一些(但不是全部)乳糜瀉患者可能會經(jīng)歷更高的焦慮癥發(fā)病率;雖然采用無麩質(zhì)飲食可能會減輕一些乳糜瀉患者的焦慮癥狀,但其他人可能會因飲食的復(fù)雜性而增加孤獨(dú)感和沮喪感。205,206最新證據(jù)不支持無麩質(zhì)飲食對那些沒有已知腹腔疾病的人減少焦慮的有用性。更多信息可在我們的腹腔疾病和非腹腔麩質(zhì)敏感性方案中。
鍛煉
運(yùn)動(dòng)和體力活動(dòng)對焦慮癥的保護(hù)和治療作用已在許多研究中得到一致證明。207,208此外,運(yùn)動(dòng)可改善身體健康,并有助于降低與焦慮癥相關(guān)的心血管問題的風(fēng)險(xiǎn),包括高血壓和早期死亡。209一篇綜述指出,高強(qiáng)度有氧運(yùn)動(dòng)項(xiàng)目在減少焦慮方面比低強(qiáng)度項(xiàng)目更有效,盡管作者警告說,運(yùn)動(dòng)方案應(yīng)根據(jù)每個(gè)人的需要進(jìn)行精心調(diào)整,以減少半途而廢的風(fēng)險(xiǎn)
睡眠
睡眠障礙和失眠是整個(gè)生命周期焦慮癥的共同特征,睡眠和焦慮之間的關(guān)系可能是雙向的。211-213事實(shí)上,睡眠中斷是包括廣泛性焦慮癥在內(nèi)的多種情緒障礙的診斷標(biāo)準(zhǔn)之一,臨床前研究表明,晝夜節(jié)律(晝夜-覺醒-睡眠周期)的中斷會導(dǎo)致類似焦慮的反應(yīng)。211睡眠不良會促進(jìn)或加強(qiáng)功能失調(diào)的思維模式和情緒調(diào)節(jié)障礙。215,216這強(qiáng)調(diào)了識別和治療睡眠障礙的根本原因的重要性,如不寧腿綜合征.214
良好的睡眠衛(wèi)生可以減少焦慮,改善整體身心健康,而不良的睡眠衛(wèi)生會加重失眠,降低睡眠質(zhì)量。睡眠衛(wèi)生包括保持一個(gè)一致的睡眠-覺醒時(shí)間表;限制飲食,屏幕時(shí)間和睡前刺激活動(dòng);限制非睡眠時(shí)間在床上;避免午睡。結(jié)合放松練習(xí)和認(rèn)知療法也可能有助于促進(jìn)睡眠。17,218睡眠支持的個(gè)體化方法可能導(dǎo)致最佳結(jié)果。219
放松
冥想和放松對情緒有獨(dú)特的影響,可能是對其他減輕焦慮癥患者癥狀的策略的有益補(bǔ)充。對16項(xiàng)使用放松療法治療焦慮癥的隨機(jī)對照試驗(yàn)進(jìn)行的薈萃分析發(fā)現(xiàn),這些療法可以減少焦慮癥患者的抑郁、恐懼和擔(dān)憂。18冥想、減壓,在多項(xiàng)研究中發(fā)現(xiàn),基于正念的認(rèn)知療法有助于改善焦慮癥患者的情緒,減少焦慮癥狀。這些療法強(qiáng)調(diào)平靜心靈,將注意力引向當(dāng)下的體驗(yàn)。220-222瑜伽也可能是治療焦慮癥的整體方法的有益部分。217
戶外活動(dòng)和接觸大自然
焦慮在生活在城市中心的人中更為常見,越來越多的證據(jù)表明這可能不是巧合。223,224腦成像研究表明,城市生活影響大腦處理社會信息和壓力,與大腦杏仁核的激活有關(guān)。224夜間照明和城市生活特有的活動(dòng)也可能干擾正常的晝夜節(jié)律周期,并導(dǎo)致功能失調(diào)的壓力信號。222其他環(huán)境因素,如工業(yè)活動(dòng)和交通,與情緒困擾增加有關(guān)。226
進(jìn)入自然環(huán)境,尤其是那些有大量樹冠或水體的環(huán)境,與較低的焦慮和抑郁率有關(guān)。226,227在一項(xiàng)研究中,歐洲城市居民報(bào)告說,在戶外自然環(huán)境中只接觸10分鐘,情緒就有所改善。228許多研究表明,即使是在城市環(huán)境中,園藝對整體健康也有積極影響,可以提高心理、身體和社會福利。
九、中西醫(yī)結(jié)合干預(yù)
L-茶氨酸
L-茶氨酸是綠茶和紅茶中的一種氨基酸,攝入后很容易穿過血腦屏障。230 L-茶氨酸有良好的放松作用,并發(fā)現(xiàn)L-茶氨酸可以減輕壓力和焦慮癥狀,改善認(rèn)知能力的某些方面。230,231一些研究表明,L-茶氨酸似乎對大腦化學(xué)有復(fù)雜的影響,表明它增加GABA水平,調(diào)節(jié)多巴胺和5-羥色胺水平,影響參與神經(jīng)興奮的NMDA谷氨酸受體的功能,并增加腦源性神經(jīng)營養(yǎng)因子(一種刺激神經(jīng)生長和神經(jīng)元間連接的蛋白質(zhì))的水平。230,232-234
在30名健康志愿者中進(jìn)行的一項(xiàng)對照試驗(yàn)發(fā)現(xiàn),每天服用200毫克L-茶氨酸,持續(xù)四周,可以改善壓力引起的焦慮、抑郁和睡眠問題,提高認(rèn)知能力。235學(xué)生在挑戰(zhàn)前一周和挑戰(zhàn)期間10天每天飲用含約15毫克L-茶氨酸的低咖啡因綠茶,與安慰劑相比,他們感受到的壓力和應(yīng)激反應(yīng)的激活更少。236在一項(xiàng)安慰劑對照試驗(yàn)中,46名廣泛性焦慮患者接受了安慰劑對照試驗(yàn)在抗抑郁藥物治療中,每天450-900毫克的L-茶氨酸可改善輕度睡眠相關(guān)癥狀患者的睡眠滿意度,降低失眠的嚴(yán)重程度。237 L-茶氨酸還可減輕重度抑郁癥和精神分裂癥患者的焦慮癥狀。238,239對9項(xiàng)對照試驗(yàn)結(jié)果的系統(tǒng)回顧得出結(jié)論,每天200-400毫克的L-茶氨酸有助于減輕處于應(yīng)激狀態(tài)的人的壓力和焦慮。240
檸檬香膏
檸檬香膏(Melissa officinalis)是薄荷植物家族的一員,歷史上用于治療焦慮、抑郁和認(rèn)知問題。241在一項(xiàng)開放性臨床試驗(yàn)中,20名具有高感知壓力水平和輕度至中度焦慮和睡眠障礙的受試者每天服用兩劑300毫克的檸檬香膏提取物,為期15天;在研究結(jié)束時(shí),70%的受試者經(jīng)歷了焦慮癥狀的緩解,85%的受試者經(jīng)歷了睡眠癥狀的緩解,70%的受試者經(jīng)歷了焦慮和睡眠問題的恢復(fù)。239安慰劑對照試驗(yàn)表明,檸檬香膏可以有效降低心悸和心絞痛患者的焦慮。243,244另一項(xiàng)包括100名患有經(jīng)前期綜合征的青春期女孩的試驗(yàn)發(fā)現(xiàn),每天服用600毫克檸檬香膏,持續(xù)三個(gè)月,比安慰劑更有效地減少焦慮和睡眠困難,改善社交能力。245
藏紅花
藏紅花(番紅花)是一種開花植物,因其烹飪用途和獨(dú)特的顏色而聞名。藏紅花提取物已在多個(gè)臨床試驗(yàn)和綜述中報(bào)道,以減少焦慮和抑郁癥狀,改善心理健康,并證明其療效與目前使用的抗抑郁藥相當(dāng)。246-250在一個(gè)安慰劑對照試驗(yàn)中,包括60名焦慮和抑郁的參與者,每天服用50毫克藏紅花,持續(xù)12周,可降低焦慮和抑郁癥狀測試的得分。248在另一項(xiàng)試驗(yàn)中,同樣有輕度至中度焦慮和抑郁癥狀的2型糖尿病患者每天服用30毫克藏紅花提取物或安慰劑,持續(xù)8周。在試驗(yàn)結(jié)束時(shí),服用藏紅花的患者癥狀明顯減輕,睡眠得到改善。252試驗(yàn)還報(bào)告了藏紅花與其他草藥提取物(包括紅景天和姜黃提取物)聯(lián)合使用的良好效果。253,254
益生菌
目前已經(jīng)證實(shí),腸道微生物群對大腦功能有著深遠(yuǎn)的影響,在調(diào)節(jié)情緒方面發(fā)揮著重要作用。255越來越多的證據(jù)支持益生菌治療情緒障礙,導(dǎo)致一些人使用“心理生物素”來描述這些有益微生物。256-258一些對照試驗(yàn)表明,含有乳酸桿菌和雙歧桿菌菌株的益生菌補(bǔ)充劑可以改善焦慮,包括壓力引起的焦慮。259在66名健康受試者的安慰劑對照試驗(yàn)中,益生菌組合L.helveticus R0052和B.longum R0175,每天30億菌落(CFU)的劑量,持續(xù)30天,減少了焦慮和抑郁的測量。260對該研究數(shù)據(jù)的第二次分析顯示,這種益生菌配方降低了感知壓力和焦慮和抑郁癥狀,即使是在那些患有最低壓力水平(由尿皮質(zhì)醇決定),表明它可能對健康人的心理健康有保護(hù)作用。258在一項(xiàng)安慰劑對照試驗(yàn)中,12周補(bǔ)充混合益生菌,每天提供1350億CFU,導(dǎo)致那些具有被認(rèn)為可能與增加心境障礙風(fēng)險(xiǎn)相關(guān)的遺傳模式的人在焦慮測試中的得分降低。262中等壓力水平的健康成年人在12周內(nèi)每天服用10億CFU植物乳桿菌DR7,壓力和焦慮得分降低,與安慰劑組比較,減少了炎癥反應(yīng)細(xì)胞因子和應(yīng)激激素水平。263在一項(xiàng)針對健康大學(xué)生的隨機(jī)對照試驗(yàn)中,益生菌減少焦慮癥狀,對基線抑郁分?jǐn)?shù)較高的學(xué)生更有效。264另一項(xiàng)試驗(yàn)發(fā)現(xiàn),在準(zhǔn)備考試的醫(yī)學(xué)生中,服用熱滅活的L.gasseri補(bǔ)充劑24周每天提供100億個(gè)細(xì)菌,比安慰劑更好地減少焦慮癥狀和改善睡眠。265
ω-3脂肪酸
在魚類中發(fā)現(xiàn)的ω-3脂肪酸,二十二碳六烯酸(DHA)和二十碳五烯酸(EPA),是大多數(shù)細(xì)胞膜的組成部分。DHA是神經(jīng)細(xì)胞中占主導(dǎo)地位的多不飽和脂肪酸,對正常的神經(jīng)系統(tǒng)功能至關(guān)重要,可以直接食用,也可以由EPA在體內(nèi)合成。Omega-3脂肪酸具有抗炎特性,在大腦中,它可以抑制應(yīng)激反應(yīng)的激活,有助于緩解焦慮和抑郁癥狀。42,266一項(xiàng)對照試驗(yàn)的回顧和薈萃分析指出,證據(jù)支持Omega-3脂肪酸的作用,劑量為每天2000毫克或更高,減少各種臨床疾病患者的焦慮。267
與健康人相比,社交焦慮癥患者紅細(xì)胞膜中的omega-3脂肪酸水平較低,268在一項(xiàng)針對抑郁癥患者的研究中,焦慮癥患者的血漿EPA和DHA水平低于無焦慮癥患者。269多項(xiàng)研究發(fā)現(xiàn),補(bǔ)充omega-3脂肪酸可以減輕焦慮癥狀。在一項(xiàng)包含68名醫(yī)學(xué)生的安慰劑對照試驗(yàn)中,每天服用2085毫克EPA和348毫克DHA,持續(xù)12周,焦慮癥狀減少了20%,炎癥標(biāo)志物水平也降低了。270在一項(xiàng)安慰劑對照試驗(yàn)中,重度抑郁癥患者的焦慮癥狀減少了20%,與服用SSRI和安慰劑的患者相比,在服用SSRI的同時(shí)服用omega-3脂肪酸的患者在12周后焦慮敏感性更低,睡眠和情緒調(diào)節(jié)也得到改善。271其他隨機(jī)對照試驗(yàn)發(fā)現(xiàn),補(bǔ)充EPA和DHA可以減輕心臟病患者,272有經(jīng)前綜合征的婦女,273和有藥物濫用史的個(gè)人焦慮癥狀。274-276
復(fù)合維生素和復(fù)合B族維生素
B族維生素是全身許多生化途徑的關(guān)鍵輔助因子,包括神經(jīng)遞質(zhì)的合成。眾所周知,低水平的B族維生素會導(dǎo)致神經(jīng)和心理障礙。277,278在一項(xiàng)針對老年人的研究中,維生素B6水平低與焦慮癥狀增加有關(guān)。279另一項(xiàng)研究發(fā)現(xiàn),在急診室就診的恐慌癥患者比健康志愿者維生素B6水平低的可能性更大。277
對對照試驗(yàn)的薈萃分析得出結(jié)論,補(bǔ)充維生素和礦物質(zhì),特別是補(bǔ)充維生素B,可以降低感知的壓力水平,減少輕度焦慮,改善整體情緒。281在健康成年人中,每周在家評估,評估超過16周的結(jié)果顯示,與對照組相比,服用復(fù)合維生素的人減少了壓力和焦慮。282一項(xiàng)包括60名抑郁癥患者的安慰劑對照試驗(yàn)發(fā)現(xiàn),服用甲基化維生素B復(fù)合物補(bǔ)充劑60天可以減少抑郁和焦慮,改善生活質(zhì)量。280
鎂
鎂具有多種功能,可能有助于緩解壓力和焦慮情緒,包括調(diào)節(jié)HPA軸活動(dòng)和降低神經(jīng)元的興奮性。284低鎂狀態(tài)可能與焦慮風(fēng)險(xiǎn)增加有關(guān),尤其是女性。一項(xiàng)針對伊朗受試者的研究發(fā)現(xiàn),鎂攝入量最高的婦女與鎂攝入量最低的婦女相比,焦慮風(fēng)險(xiǎn)降低39%。285一項(xiàng)針對126名輕中度抑郁癥患者的對照試驗(yàn)發(fā)現(xiàn),補(bǔ)充氯化鎂,每天提供248毫克元素鎂,六周后,抑郁和焦慮癥狀量表得分下降。283對臨床試驗(yàn)的系統(tǒng)回顧發(fā)現(xiàn),有證據(jù)表明,鎂單獨(dú)或與維生素B6或草藥提取物聯(lián)合使用,可減輕輕度至中度焦慮、經(jīng)前期綜合征患者的焦慮癥狀,或高血壓。287 L-蘇氨酸鎂是鎂的一種氨基酸結(jié)合形式,已被發(fā)現(xiàn)在焦慮動(dòng)物模型中對提高大腦鎂水平、促進(jìn)神經(jīng)可塑性和抑制恐懼反應(yīng)特別有效。288,289
L-色氨酸和5-羥基色氨酸(5-HTP)
L-色氨酸是腸和腦產(chǎn)生5-羥色胺所必需的氨基酸和前體。287它被認(rèn)為在腸和腦之間的交流中起著重要作用。292在急性應(yīng)激的健康成年人中,L-色氨酸轉(zhuǎn)化為5-羥色胺的效率已被證明較低。293
幾十年來,L-色氨酸一直用于提高血清素水平,以改善情緒和睡眠。290對11項(xiàng)對照試驗(yàn)結(jié)果的系統(tǒng)回顧發(fā)現(xiàn),每天劑量高達(dá)3克的L-色氨酸可以減少健康人的焦慮,增加積極情緒。291
5-羥基色氨酸(5-HTP)是5-羥色胺的直接前體。人們主要研究了5-HTP的抗抑郁作用,292一些研究表明5-HTP對焦慮癥也有幫助。在一項(xiàng)安慰劑對照試驗(yàn)中,驚恐障礙患者服用200mg 5-HTP后對驚恐誘導(dǎo)刺激的反應(yīng)較少。297 5-HTP對驚恐和其他焦慮障礙患者的有益作用也有報(bào)道。298,299此外,5-HTP的劑量為200-400mg/天,已經(jīng)發(fā)現(xiàn)可以減少纖維肌痛綜合征患者的焦慮癥狀。300,301大多數(shù)關(guān)于精神疾病背景下5-HTP的研究質(zhì)量值得懷疑,因此有必要進(jìn)行進(jìn)一步的嚴(yán)格研究。302
褪黑素
褪黑素是大腦中產(chǎn)生的一種激素,參與晝夜節(jié)律的調(diào)節(jié),并對情緒、疼痛和睡眠產(chǎn)生影響。303臨床前研究表明,褪黑素受體參與焦慮、抑郁和睡眠障礙的機(jī)制。304
大量確鑿的證據(jù)表明,褪黑素有助于促進(jìn)睡眠,并對一系列精神、神經(jīng)和身體狀況的改善具有很大的前景。305-307在多個(gè)安慰劑對照試驗(yàn)中發(fā)現(xiàn)褪黑素可減少術(shù)前和術(shù)后焦慮。305,308基于褪黑素和褪黑素受體發(fā)揮作用的證據(jù)在焦慮中的重要作用,褪黑素類藥物阿戈美拉汀,已被提出作為一種新興的治療焦慮癥的藥物(見新興的和新穎的治療)。
N-乙酰半胱氨酸
N-乙酰半胱氨酸(NAC)是氨基酸半胱氨酸的前體,半胱氨酸是人體主要抗氧化劑之一谷胱甘肽的氨基酸成分。它還具有固有的自由基猝滅能力和抗炎特性
對患有創(chuàng)傷后應(yīng)激障礙和藥物使用障礙的退伍軍人進(jìn)行的一項(xiàng)安慰劑對照試驗(yàn)發(fā)現(xiàn),每天服用2400毫克NAC,同時(shí)接受認(rèn)知行為治療8周,可以減少心理癥狀和食欲;其中許多效果在治療結(jié)束后一個(gè)月仍很明顯。309一些試驗(yàn)也注意到,NAC的使用與強(qiáng)迫癥和相關(guān)疾病患者的強(qiáng)迫癥和強(qiáng)迫行為的減少有關(guān),這些患者有大量的焦慮成分。310,311此外,對照試驗(yàn)表明,NAC可減輕一系列心境障礙患者的抑郁癥狀。312
薰衣草
薰衣草是薄荷科的一種植物,以其特有的香味而聞名。薰衣草在歐洲被批準(zhǔn)用作治療焦慮和壓力的植物藥,它的精油也被用于同樣條件下的芳香療法。它似乎通過激活副交感神經(jīng)系統(tǒng)來促進(jìn)放松、影響血清素信號和降低神經(jīng)興奮性而發(fā)揮作用。313,314薰衣草的芳香療法應(yīng)用可能對立即緩解癥狀更有效,但口服薰衣草制劑在長期治療中似乎有更好的療效。315
一項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析發(fā)現(xiàn),薰衣草芳香療法可以減少焦慮,降低收縮壓,降低心率,降低唾液皮質(zhì)醇水平(一種被激活的應(yīng)激反應(yīng)的量度)。316它對焦慮癥狀的積極影響已經(jīng)在不同的環(huán)境中得到證實(shí),包括癌癥護(hù)理期間、重癥監(jiān)護(hù)期間、牙科或其他手術(shù)期間以及健康志愿者。盡管有這些發(fā)現(xiàn),更好的薰衣草治療焦慮癥的試驗(yàn)仍然需要進(jìn)行。317-319在對四項(xiàng)臨床試驗(yàn)的回顧中發(fā)現(xiàn),芳香療法和薰衣草制劑的補(bǔ)充都可以改善更年期婦女和老年婦女的睡眠困難和其他更年期癥狀。320在一項(xiàng)60名老年參與者的對照試驗(yàn)中,每天喝兩次薰衣草茶,持續(xù)兩周,可以減少焦慮和抑郁的癥狀。317喝茶可以結(jié)合薰衣草的芳香療法和內(nèi)部藥物作用。
Silexan是一種標(biāo)準(zhǔn)化的薰衣草花精油產(chǎn)品,目前在德國被批準(zhǔn)用于治療焦慮相關(guān)的躁動(dòng)。許多臨床試驗(yàn)已經(jīng)研究了silexan對焦慮癥、亞臨床焦慮癥和與焦慮相關(guān)的癥狀,如睡眠困難的作用。322一項(xiàng)臨床試驗(yàn)的結(jié)果表明,其促進(jìn)睡眠的能力與其鎮(zhèn)靜作用有關(guān),不如說與抗焦慮作用有關(guān)。323五項(xiàng)隨機(jī)對照試驗(yàn)的薈萃分析發(fā)現(xiàn),645名焦慮癥患者接受了9-12周的silexan治療與標(biāo)準(zhǔn)SSRI(帕羅西?。┫啾?,80 mg/天的silexan在減輕癥狀方面同樣有效,160 mg/天更有效。322另一項(xiàng)薈萃分析包括三項(xiàng)隨機(jī)對照試驗(yàn),其中697名焦慮低于焦慮癥診斷閾值的患者接受80 mg/天的silexan治療10周;研究發(fā)現(xiàn),治療在減少焦慮和改善睡眠方面比安慰劑更有效。324
西番蓮
西番蓮(Passiflora importanata)是西歐草藥中的一種重要草藥,傳統(tǒng)上用于治療焦慮、睡眠障礙和煩躁不安。325,326西番蓮具有與增強(qiáng)GABA信號相關(guān)的溫和鎮(zhèn)靜作用。327
在一項(xiàng)隨機(jī)對照試驗(yàn)中,對36例廣泛性焦慮癥患者進(jìn)行了西番蓮與苯二氮卓(奧沙西泮[Serax])的比較,發(fā)現(xiàn)這兩種治療都能減輕焦慮癥狀;然而,盡管奧沙西泮起效更快,但他有更大的負(fù)面影響。328發(fā)現(xiàn)西番蓮在牙科手術(shù)前緩解焦慮方面也與苯二氮卓類藥物咪達(dá)唑侖(Versed)一樣有效。329其他對照試驗(yàn)發(fā)現(xiàn)西番蓮可以在其他類型的手術(shù)前降低焦慮。330-332在一項(xiàng)對照試驗(yàn)中發(fā)現(xiàn),睡前喝西番蓮茶是有效的,在改善輕度睡眠障礙受試者的睡眠方面比安慰劑更有效。329
纈草
纈草(valerianaofficinalis)是一種藥用植物,長期以來一直被用作溫和的鎮(zhèn)靜劑,用于治療躁動(dòng)和焦慮。纈草中的活性化合物似乎通過與GABA受體相互作用發(fā)揮舒張作用。334
在一項(xiàng)針對31名強(qiáng)迫癥患者的安慰劑對照試驗(yàn)中,每天765毫克纈草提取物持續(xù)8周,有效地改善了癥狀,發(fā)現(xiàn)500mg劑量的纈草提取物也可以降低即將接受侵入性婦科診斷程序的婦女的焦慮。332一些額外的研究得出結(jié)論,纈草在不同的環(huán)境下具有適度的抗焦慮和放松作用。337-340
γ-氨基丁酸
在神經(jīng)系統(tǒng)中,γ-氨基丁酸(GABA)是一種神經(jīng)遞質(zhì),是神經(jīng)信號傳遞的主要抑制劑。苯二氮卓類藥物,有時(shí)用于治療焦慮和壓力相關(guān)疾病,靶向某些GABA受體。342
在一項(xiàng)臨床研究中,口服GABA補(bǔ)充劑被發(fā)現(xiàn)能在一小時(shí)內(nèi)增加健康志愿者大腦中的α波活性,降低β波活性,表明GABA能引起放松和減少焦慮。343一項(xiàng)對63名成年人進(jìn)行的安慰劑對照試驗(yàn)發(fā)現(xiàn),在完成一項(xiàng)精神任務(wù)前30分鐘服用100毫克GABA可減少大腦活動(dòng)中與壓力有關(guān)的變化。344一項(xiàng)對10名有輕度睡眠問題的健康受試者進(jìn)行的隨機(jī)對照試驗(yàn)發(fā)現(xiàn),在睡前30分鐘服用100毫克GABA,持續(xù)一周與安慰劑相比,睡眠時(shí)間縮短,睡眠質(zhì)量提高。341由于睡眠問題、壓力和焦慮經(jīng)常同時(shí)發(fā)生,GABA可能有助于治療這類疾病。
賴氨酸和精氨酸
在動(dòng)物模型中,必需氨基酸L-賴氨酸已被證明與5-羥色胺和GABA受體相互作用,單獨(dú)或與L-精氨酸聯(lián)合使用可改善焦慮。346,347賴氨酸抗焦慮特性的另一潛在作用機(jī)制是降低皮質(zhì)醇和神經(jīng)張力。在一項(xiàng)隨機(jī)對照研究中,用賴氨酸強(qiáng)化小麥可降低男性的慢性焦慮,降低女性對應(yīng)激事件的皮質(zhì)醇反應(yīng)。350在另一項(xiàng)隨機(jī)對照試驗(yàn)中,29名具有焦慮個(gè)性的健康個(gè)體分別用3克賴氨酸和L精氨酸治療10天,然后暴露在社會壓力之下。應(yīng)激激素水平提高了,參與者管理壓力的能力也提高了。351在一項(xiàng)安慰劑對照試驗(yàn)中,招募了107名健康志愿者,每天服用2.64克賴氨酸和L-精氨酸,持續(xù)一周,男性和女性的應(yīng)激性焦慮和焦慮總體上都有所降低。氨基酸組合也降低了生理應(yīng)激的標(biāo)記物. 347
卡瓦
卡瓦(胡椒)是黑胡椒科的一種植物,原產(chǎn)于南太平洋,幾個(gè)世紀(jì)以來一直被用作松弛劑??ㄍ咚坪踽槍π尤屎撕推渌婕翱謶趾蛽?dān)憂的大腦區(qū)域,并可能通過改變神經(jīng)遞質(zhì)信號來促進(jìn)放松。348一些對照試驗(yàn)的薈萃分析發(fā)現(xiàn),卡瓦在使用長達(dá)24周時(shí),有效且安全地減輕焦慮癥狀。352-355一項(xiàng)臨床試驗(yàn)回顧發(fā)現(xiàn),在患者中對于廣泛性焦慮癥,卡瓦提取物每天提供120-280毫克的卡瓦內(nèi)酯(卡瓦的生物活性化合物),持續(xù)4-8周是安全的,可以減輕癥狀。352
注:在極少數(shù)情況下,使用卡瓦會產(chǎn)生嚴(yán)重的副作用,包括皮膚反應(yīng)、認(rèn)知問題和肝損傷,因此應(yīng)仔細(xì)監(jiān)測其使用情況。357,358
其他草藥療法
許多草藥因其對神經(jīng)系統(tǒng)的放松作用而受到重視。在安慰劑對照試驗(yàn)中,一種草藥含有山楂(山楂)和加利福尼亞罌粟(Eschscholzia californica)的提取物以及鎂,被發(fā)現(xiàn)對輕度到中度的廣泛性焦慮患者有益。359 Galphimia(Galphimia glauca)是一種墨西哥草藥,傳統(tǒng)上用于治療焦慮和抑郁以及焦慮癥其他條件的范圍。三項(xiàng)動(dòng)物試驗(yàn)證實(shí)了組成的galphimines和相關(guān)化合物的抗焦慮作用。三個(gè)隨機(jī)對照臨床試驗(yàn)比較了galphimia提取物與焦慮藥物,SSRI或苯二氮卓。所有三個(gè)試驗(yàn)都表明,galphimia的療效與處方藥相當(dāng)或優(yōu)于處方藥。360,361草藥提取物,如洋甘菊(Matricicaria recutita)、菩提花(如紫椴)、啤酒花(Humulus lupulus)、薄荷、黑升麻(Cimicifuga racemosa)、檸檬馬鞭草(Aloysia citriodora),荊芥(Vitex agnus castus)可能有助于治療焦慮及相關(guān)癥狀。22,23,362
本文提出了許多問題,這些問題可能會隨著新數(shù)據(jù)的出現(xiàn)而發(fā)生變化。 我們建議的營養(yǎng)或治療方案均不用于確保治愈或預(yù)防任何疾病。Piping Rock健康研究院沒有對參考資料中包含的數(shù)據(jù)進(jìn)行獨(dú)立驗(yàn)證,并明確聲明對文獻(xiàn)中的任何錯(cuò)誤不承擔(dān)任何責(zé)任。
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