抗抑鬱藥
抗抑鬱藥(英語:Anti-depressant),是一類治療重度抑鬱症(MDD)或其它問題如心境惡劣障礙、焦慮症、強迫症、進食障礙、慢性疼痛、神經性疼痛的藥物,在某些情況下也可以用來治療痛經、打鼾、偏頭痛、多動症(ADHD)、藥物濫用和失眠。抗抑鬱藥可以單獨使用,也可以與其他藥物聯用,但都要遵醫生的處方使用。
主要的抗抑鬱藥有選擇性5-羥色胺再攝取抑制劑(SSRI)、5-羥色胺和去甲腎上腺素再攝取抑制劑(SNRI)、三環類抗抑鬱藥(TCA)、單胺氧化酶抑制劑(MAOI)、四環類抗抑鬱藥(TeCA)、去甲腎上腺素和特異性5-羥色胺能抗抑鬱藥(NaSSA)。其他不常用的抗抑鬱藥有丁丙諾啡[1]、低劑量抗精神病藥[2]和聖約翰草提取物。[3][4]
一種關於抑鬱症成因的理論認為,抑鬱症以與下丘腦-垂體-腎上腺軸(HPA軸)在應激狀態下出現的神經-內分泌反應類似的過度活躍為特徵。HPA軸的異常參與抑鬱症狀的形成,而抗抑鬱藥可能起着調控HPA軸的作用。[5]
醫學應用
[編輯]常用漢密爾頓抑鬱量表(HAM-D)來評估抑鬱症症狀的嚴重程度。[6] HAM-D量表共有17個項目,最高分為52分。分值越高,抑鬱越嚴重。
臨床準則
[編輯]英國國家衛生與保健研究所(NICE)於2009年發佈的方針指出,因風險效益比過低,抗抑鬱藥不應被例行地用於輕度抑鬱的初步治療。方針建議,應對下列情形考慮進行抗抑鬱藥治療:
- 有中度或重度抑鬱病史的人
- 長期患有輕度抑鬱的人
- 作為對採用其他治療方案後仍然存在的症狀的二線療法
- 作為中度或重度抑鬱症的一線療法
方針還指出,抗抑鬱藥在大多數情況下應與心理社會學治療結合使用,在病癒後繼續治療至少6個月以避免復發,而且SSRI類藥物的耐受性比其他類抗抑鬱藥更好。[7]
美國精神醫學學會的治療方針建議,初步的治療方案應基於症狀的嚴重程度、並發疾病、之前的治療經歷以及病人的偏好而量身定製。可選的療法包括藥物療法、心理療法、電痙攣療法(ECT)、經顱磁刺激(TMS)及光療。對輕度、中度、重度抑鬱患者,推薦將抗抑鬱藥作為一線治療方案,並且對無計劃進行ECT的重度抑鬱患者都應採用抗抑鬱藥治療。[8]
系統性評估
[編輯]針對患有急性輕度或中度抑鬱的人群進行的一些將抗抑鬱藥效果與安慰劑作比較的研究結論存在矛盾。有較強證據證明,抗抑鬱藥在對慢性或重度抑鬱的治療當中起了重要作用。
Irving Kirsch和Thomas Moore等人對抗抑鬱藥的藥理學活性提出質疑,稱證據表明抗抑鬱藥的作用與具活性的安慰劑的效果類似。[9] 研究結果通過對公開發表的研究數據及通過FOIA獲取的非公開FDA數據進行元分析而得出。整體上,抗抑鬱藥的效果比安慰劑好18%,具有統計學意義,但不具臨床意義。[10] 在後來發佈的一項研究中,Kirsch得出結論,新一代抗抑鬱藥物的總體效果未能達到臨床標準。[11]
2017年發表的一項將SSRI類抗抑鬱藥物與安慰劑進行比較的元分析發現,在49項相關研究中,使用SSRI類藥物後漢密爾頓抑鬱量表的分值平均下降了1.9分,具統計學意義,但未能達到臨床標準。該臨床標準由英國國家衛生與保健研究所制定,該標準要求標準平均差至少為0.5,即量表得分下降3分。不過,這項研究有着較高的偏差風險,或許可以用來解釋SSRI類藥物具有統計學意義的效果。最終,作者得出結論,負面效應發生的頻率使得本就較不顯著的臨床症狀改善失去了意義。[12]
在一次關於抗抑鬱藥效果的元分析中發現,抗抑鬱藥的效果(以HDRS分數衡量)與抑鬱的嚴重程度有關。對於得分低於23分(表明患有輕度至中度抑鬱)的患者,抗抑鬱藥效果僅比安慰劑略強。然而,對於分值大於25的患者,抗抑鬱藥表現出了明顯強於安慰劑的效果,超出了NICE設定的臨床意義閾值。[13]
另一項着眼於帕羅西汀與丙咪嗪的研究發現,對於輕度或重度抑鬱,抗抑鬱藥僅比安慰劑略好,但對嚴重抑鬱則有顯著療效。[14]
2014年,美國FDA發表了一項對1985至2012年間提交給該機構的全部抗抑鬱藥維持性臨床試驗(maintenance trials)進行的系統性評估。作者得出結論,比起安慰劑,維持性治療將復發風險降低了52%,並且主要與安慰劑組抑鬱症復發有關,而非因藥物戒斷反應而產生。[15]
NICE資助的一項評估發現,有強有力的證據證明SSRI類藥物比起安慰劑來能更有效地降低中度至重度抑鬱症患者的HDRS分數,對輕度抑鬱患者來說也有一定證據能證明此效應。基於這項研究而提出的治療方針建議,應對中度至重度抑鬱患者及那些輕度抑鬱症狀持續且對其他治療方案不敏感的患者採用抗抑鬱藥治療。[16]
考科藍合作組織最近對三環類抗抑鬱藥阿米替林的臨床試驗進行了系統性的評估。儘管有證據表明發表偏差的存在,但研究仍然得出結論,有大量證據表明阿米替林比安慰劑效果更好。[17]
2015年,一項對耐受其他治療方案的抑鬱症狀進行的增強療法(add-on therapy)進行的系統性評估得出結論,喹硫平和阿立哌唑有最充分的證據證明其功效,但這兩種藥物都造成了一些與治療相關的副作用。 [18]
2008年的考科藍合作組織一項對貫葉連翹(更確切地說,是一切貫葉連翹提取物)進行的評估以及2015年由先前研究的部分作者合作進行的一項元分析系統性評估得出同樣結論,貫葉連翹功效強於安慰劑,與標準抗抑鬱藥相比同樣有效,且有着更少的副作用。2015年的元分析得出結論,因證據有限,且德語區與其他語言區進行的臨床試驗間功效存在較大差異,難以在抑鬱症治療方案當中為貫葉連翹找到一個合適位置。[19][3] 有證據顯示,可逆性單胺氧化酶抑制劑(RIMAs)也是一種有效的治療藥物,其耐受性較其他抗抑鬱藥更佳。[19]然而,比起貫葉連翹、可逆性單胺氧化酶抑制劑、5-羥色胺和去甲腎上腺素再攝取抑制劑、羥色胺拮抗和再攝取抑制劑、去甲腎上腺素再攝取抑制劑、去甲腎上腺素和特異性5-羥色胺能抗抑鬱藥等藥物,SSRI類、 三環類、四環類抗抑鬱藥有着更多證據支持其在治療抑鬱中的作用。[19]
發表於《美國醫學會雜誌》(JAMA)的一項研究表明,在抗抑鬱藥臨床試驗中,安慰劑效應越來越顯著,而被測藥物的效果則沒有較大變化。作者表示,因社會對使用抗抑鬱藥的負面態度有所改善,更多輕度、短期或突然復發的抑鬱症患者參與了實驗,可能可以用來解釋這一現象。[20]在補充與替代(CAM)療法的臨床試驗中,安慰劑的起效率明顯低於傳統抗抑鬱藥。[21]
2004年的一項評估得出結論,那些沒能支持抗抑鬱藥功效的研究成果,比起支持抗抑鬱藥功效的研究成果更少被發表。[22]對針對兒童使用抗抑鬱藥的臨床試驗的研究也獲得了類似結論。[23]2015年,在一次對抗抑鬱藥相關研究的元分析的調查當中發現,79%的研究存在「接受來自製藥企業的贊助、以製藥企業員工為作者以及存在相關利益衝突」等現象。 [24]
2012年的一次元分析發現氟西汀及文拉法辛對全部年齡組的重性抑鬱障礙患者均有效,同時沒有發現證據能夠支持抑鬱症狀的嚴重程度與採用藥物治療後的效果存在關係。[25]
2012年發表的一項研究發現,研究持續的時間與抗抑鬱藥的功效(以起效率衡量)之間呈負相關關係。抗抑鬱藥的起效率變化主要是安慰劑起效率的提高造成的。但是,作者仍然認為抗抑鬱藥能有效地治療抑鬱症。[26] 作者發現,三環類藥物是最有效的一類藥物,其次是SNRI類、MAOI類、SSRI類及非常規抗抑鬱藥。
STAR*D臨床試驗
[編輯]史上規模最大、最昂貴的針對抑鬱症藥物療法的有效性的研究由美國國家心理衛生研究所主持進行。[27]這項研究被稱作「抑鬱症的有序治療備選方案」(STAR*D)。結果[28][29]如下。 患者在一般性或精神類醫療機構就診時被召募參與實驗。實驗未發佈志願者招募廣告,以最大化研究結果的普適性。患者的HAM-D得分至少須為14分才可參加實驗。按照通行標準,7-17分歸類為輕度抑鬱,18-24分歸類為中度抑鬱,24分及以上為重度抑鬱。[30]參與者的HAM-D17分值平均為22分。[31]研究終點預先定義為抑鬱症的完全康復(根據HAM-D分數判斷),未再次參與測試的患者歸類為無回應者。在這場臨床試驗之後,研究者們主要使用QIDS-SR16分數呈現結果,而該分數常常較HAM-D分數偏高。
- 在第一療程結束之後,2876位參與者中有27.5%達到了康復標準,HAM-D分值降至了7或更低,按照QIDS-SR量表,則有33%的患者康復,起效率為47%。26%的人退出了實驗。[32][33]
- 第二療程之後,餘下的1439位參與者中,大約有21%至30%症狀大幅減輕。[29]更換藥物能使約25%的患者康復。[31][34]
- 第三療程之後,310名參與者中17.8%的人症狀減輕。[來源請求]
- 第四療程之後,109名參與者中10.1%的人症狀減輕。[來源請求]
- 第一療程中康復的患者復發率為33%,後續療程康復的患者復發率從42%到50%不等。未能完全康復的患者復發率高於完全康復患者。[35]
未發現實驗中所使用藥物存在統計學或臨床意義上的康復率、起效率、復發率差異。[36]實驗藥物包括:緩釋安非他酮、安非他酮、西酞普蘭、鋰、米氮平、去甲替林、舍曲林、三碘甲狀腺氨酸、反苯環丙胺、緩釋文拉法辛。[需要可靠醫學來源]
2008年對隨機對照試驗的一次評估發現,儘管SSRI緩解抑鬱症狀的效果在用藥第一周結束時最為顯著,但在至少六周之內,持續用藥都對症狀有所改善。[37]
制約與策略
[編輯]每種藥物都對約30%至50%的患者無效。[38][39]在臨床研究當中,大約三分之一的患者完全康復,三分之一的患者症狀有一定改善,還有三分之一的患者用藥無效。部分康復的標準基於一些定義模糊的殘餘症狀而定,這些症狀通常包括:心情壓抑,心理焦慮,睡眠不穩,疲勞及興趣、樂趣程度的下降。目前不確定什麼因素造成了部分康復的出現。然而通過這些殘餘症狀可以很準確地預測復發可能性,部分康復的患者的復發率比完全康復的患者復發率高3到6倍。[40]抗抑鬱藥的功效會隨着治療過程的持續不斷降低。[41] 根據CDC的數據,正在服用抗抑鬱藥的美國成年人中,僅有不到三分之一的人在最近一年內與精神疾病方面的專業人士見過面。[42]為了應對這些制約因素與變化,臨床實踐中也採用了一些策略,如更換藥物,採用增強療法、組合療法等。[43]
「試錯法」更換藥物
[編輯]美國精神醫學學會2000年的治療方針建議,當一種抗抑鬱藥使用6-8周後仍無效時,應首先更換為同類型的其他藥物,再更換成其他類型藥物。 2006年的元分析發現,同類實驗的結論相差較大,在對某種SSRI類藥物不敏感的患者中,有12%到86%的人對另一種藥物敏感。但是,一個人嘗試過的抗抑鬱藥種類越多,就越不可能從臨床試驗中獲益。[39] 然而,後來的一項元分析發現,更換新藥與持續服用原先的藥沒有區別,雖然34%的病人對新藥敏感,但40%的病人未更換新藥也有了效果。[44]
增強與組合
[編輯]對於部分起效的情況,美國精神醫學學會方針建議採用增強療法,或在治療方案中加入另一類藥物。這些藥物包括鋰、甲狀腺增強(augmentation)、多巴胺受體激動劑、性類固醇、NRI類藥物、糖皮質激素專一性製劑以及較新的抗驚厥藥。[45]
組合策略通過引入另一種抗抑鬱藥(通常為另一種類型)來影響人體的其他相關機制。儘管臨床實踐中可能採用這種策略,並沒有確切證據能夠證明這種策略的相對療效和負面作用。[46]近來進行的一些增強療法測試還將興奮劑納入了測試範圍。多項研究顯示,將莫達非尼與抗抑鬱藥組合使用對耐受常規治療的病人有着更好的效果。這一方法已被用於應對使用SSRI類藥物所引起的疲勞症狀。[47]
長期使用
[編輯]在治療結束後,抗抑鬱藥的治療效果往往也會同時消失,這也造成了抑鬱症較高的復發率。2003年,對31項以安慰劑為對照的抗抑鬱藥臨床試驗(多數隻持續1年)進行的元分析發現,18%的患者在服用曾有效的抗抑鬱藥的過程中就已復發,而在換服安慰劑的對照組中,這一數據為41%。[48]
在少數人的治療過程中,抗抑鬱藥的治療效果會逐漸減弱。[49][50]一些研究還提出一種方案,即採用藥物治療急性抑鬱症發作再轉用心理方法進行康復治療。[51][52]
相對功效與耐受性
[編輯]焦慮症
[編輯]廣泛性焦慮障礙
[編輯]焦慮症是一種以對某些事情的過分擔憂為特點的常見疾病。國家衛生與保健研究所建議,在使用保守療法如教育、自助活動治療焦慮症無效時,可採用抗抑鬱藥進行治療。
抗抑鬱藥能一定程度上減輕焦慮症狀,[73]在焦慮症的治療中效果優於安慰劑。[74]不同類型的抗抑鬱藥功效差別不大。[73][74]
強迫症
[編輯]對功能障礙不大的成年強迫症患者的二線治療、對具有中等、嚴重的功能障礙的強迫症患者的一線治療均會使用SSRI類藥物。對具有中等、嚴重的功能障礙的兒童強迫症患者的二線治療使用SSRI類藥物時需要密切監控精神類副作用。[75]SSRI類藥物用於強迫症治療時效果顯著,SSRI組的起效率兩倍於安慰劑。[76][77]在短期(6到24周)和中斷式(28到52周)臨床試驗中,均已證明抗抑鬱藥的功效。[78][79][80]
進食障礙
[編輯]抗抑鬱藥被推薦作為治療神經性暴食症的自助項目中備選或額外的第一步。[81]因SSRI類藥物(尤其是氟西汀)可接受性和耐受性更好、短期臨床試驗中症狀緩解程度更大,常選擇此類藥物而非其它抗抑鬱藥。長期功效不明確。因安非他酮可能提高癲癇發病風險,不建議使用該藥治療進食障礙。[82]
對於過胖暴食症,相同的建議同樣適用。[81]SSRI類藥物短期內可減輕過胖暴食症的症狀,但未發現其有降低體重的作用。[83]
多數臨床試驗結果否定了SSRI類藥物在神經性厭食症治療中的作用。[84]國家衛生與保健研究所(NICE)的治療方針[81]不建議在對該種疾病的治療中使用SSRI類藥物。美國精神醫學學會的方針指出,儘管SSRI類藥物對體重增長無促進作用,但仍可用來治療與該症並發的抑鬱症、焦慮症以及強迫症。[83]
疼痛
[編輯]纖維性肌痛
[編輯]2012的一次元分析得出結論,抗抑鬱藥療法改善了纖維性肌痛患者的疼痛、健康相關的生活質量、抑鬱和睡眠情況。三環類抗抑鬱藥似乎是最有效的一類抗抑鬱藥,對疼痛和睡眠有一定改善,對疲勞和生活質量也有較小的改善。使用三環類藥物的患者中,48%的人疼痛減輕了30%以上,而安慰劑組為28%;使用SSRI類藥物的患者中,36%的人疼痛減輕了30%以上,而安慰劑組為20%;使用SNRI類藥物的患者中,42%的人疼痛減輕了30%以上,而安慰劑組為32%。因副作用而中止實驗的現象較為普遍。[85]阿米替林、氟西汀、度洛西汀、米那普侖、嗎氯貝胺和吡吲哚基於「有限證據」被歐洲抗風濕聯盟推薦用於纖維性肌痛的治療。[86]
神經性疼痛
[編輯]2014年,考科藍合作組織的一次元分析發現,度洛西汀可有效治療糖尿病神經病變所造成的神經性疼痛。[87]該組織還評估了阿米替林在治療神經性疼痛中的作用,但有效的隨機化臨床試驗數據有限。他們得出結論,阿米替林長期以來在醫學中的成功應用可以在某種程度上證明該藥的有效性,[88]但也對過高估計阿米替林緩解疼痛的效果的可能性感到擔憂,並且表示只有少數人在使用該藥後能感到疼痛明顯減輕。[88]
負面影響
[編輯]一般情況
[編輯]幾乎所有涉及血清素調控的藥物都有可能引發血清素綜合症——可造成狂躁、不安、焦慮、情緒不穩、失眠和迷惑的血清素濃度過高現象。[89][90] 這種情況很嚴重,但並不常見,通常在劑量較高或同時服用多種藥物的時候發生。如果及時(24小時以內)進行醫療干預,很少致命。[91][92]
單胺氧化酶抑制劑常與許多處方/OTC藥物存在明顯(有時致命)的藥物相互作用。如果與酪胺含量非常高的食物(如成熟奶酪、醃肉或酵母提取物)同食,可能造成有致命風險的高血壓危象。劑量較低時,患者可能只會被高血壓造成的頭痛困擾。[93]
作為對這些不良反應的回應,另一種單胺氧化酶抑制劑被開發出來:單胺氧化酶A可逆性抑制劑(RIMA)類藥物。它們的主要優勢是不需要患者堅持按一個特殊食譜進餐。此外,其功效據稱與SSRI類和三環類藥物同樣有效。[94]
懷孕
[編輯]基於不同程度可信度的因果關係證明,懷孕時使用SSRI類藥物有一定風險。鑑於抑鬱症本身獨立與負面的妊娠結局相關,確定通過觀察得出的抗抑鬱藥使用與特定不良結果間的關係是否是因果關係在某些情況下較為困難。[95]在另外一些情況下,抗抑鬱藥的使用看起來與負面結果明顯相關。
懷孕中SSRI的使用不僅與自然流產發生率增長至原先1.7倍有關,[96][97]還與早產與低出生體重有關。[98]
一項針對使用了抗抑鬱藥的妊娠期的系統性評估發現,嚴重畸形的風險有小幅(3%到24%)提高,而心血管先天畸形的發生風險沒有顯著區別。[99]對使用了氟西汀的妊娠期的研究發現嚴重畸形的風險提高了12%,剛好未能達到具有統計學意義的標準。[100]其他研究發現,未接受SSRI類藥物治療的母親生下的孩子患心血管先天畸形的風險較高,提示可能存在以偏概全的現象,即擔心孩子健康的母親們可能會要求對自己的孩子做更詳盡的測試。[101] 另一項研究發現使用SSRI類藥物後,嚴重畸形的風險提高了27%,而心血管先天畸形的風險無變化。[97]FDA建議,因帕羅西汀及MAOI類藥物可提高先天畸形的風險,應避免在懷孕時使用這兩類藥物。[102]
2013年的系統性評估與元分析發現,妊娠過程中抗抑鬱藥的使用只與某些妊娠結局(胎齡、早產)的出現有統計學相關性。這項研究還指出,因使用組與未使用組之間差異較小,並不能確定其是否具有臨床意義。[103]
新生兒(出生後28天以內)可能會受停藥綜合症影響。抗抑鬱藥已被證明在母乳中以不同濃度出現,但其對新生兒的影響尚不明確。[104]
此外,SSRI類藥物還會抑制一氧化氮的合成,而該物質的合成在血管張力的調節中有重要作用。多項研究指出,SSRI的使用與早產的發生有聯繫,可能是由於子癇前症發生的風險有所提高。[105]
誤用於躁鬱症導致病情惡化
[編輯]許多躁鬱症病例與重性抑鬱障礙十分類似。因此,躁鬱症患者可能被誤診為重性抑鬱障礙患者,並被開具抗抑鬱藥處方。研究顯示,對於躁鬱症患者,抗抑鬱藥引發狂躁的發病率可達到20至40%。[106] 目前無可信證據表明對於抑鬱症患者抗抑鬱藥物可誘發狂躁,但對於躁鬱症,抗抑鬱藥(多為SSRI類藥物)可以引發或加劇狂躁的症狀。[107]
自殺
[編輯]研究顯示,對於25歲以下的人群,抗抑鬱藥的使用與出現自殺想法與行為的風險增加相關。[108]問題足夠嚴重,以至於FDA發佈了針對採用抗抑鬱藥治療時自殺風險提高的警告。[109]FDA表示,自殺風險提高這一現象主要出現在治療的前一至兩個月中。[110][111]國家衛生與保健研究所認為,自殺風險的提高主要出現在「治療前期」。[112]元分析提示,抗抑鬱藥的使用與自殺風險的提高之間的關係與年齡有關。[108]與安慰劑相比,使用抗抑鬱藥在25歲以下人群中與自殺風險的增加(優勢比=1.62)有關。此數據與在兒童及青少年人群中觀察得到的數據一致。對25歲至64歲間的人群沒有影響或是有輕微保護作用(優勢比=0.79)。65歲及以上人群使用抗抑鬱藥有保護作用(優勢比=0.37)。[108][113]
對性功能的負面影響
[編輯]SSRI類藥物在性方面的副作用也很常見,例如性衝動減弱、性快感缺失及勃起功能障礙。[114]雖然這些症狀通常是可逆的,但在一些罕見情況下,停藥後這些副作用可能持續數月甚至數年。[115]
在對1022位門診病人的研究中,對於全部抗抑鬱藥來說性功能障礙的發生率平均為59.1%。[116]SSRI類藥物的發生率在57%到73%之間, 米氮平為24%,奈法唑酮為8%,阿米庚酸為7%,嗎氯貝胺為4%。嗎氯貝胺,一種選擇性、可逆性MAO-A抑制劑,不僅不易造成性功能障礙,[117]還能帶來性功能的改善。[118]
被認為是性功能障礙可能原因的生物化學機制包括:血清素濃度的升高(對5-HT2受體、5-HT3受體的影響尤其顯著)、多巴胺濃度下降、去甲腎上腺素濃度下降、乙酰膽鹼受體和α1型腎上腺素受體受到阻滯、一氧化氮合成酶的抑制、催乳素濃度的提高。[119]根據報告,米氮平性方面副作用較少,可能是因為它拮抗5-HT2和 5-HT3型受體,並在某些情況下逆轉SSRI類藥物通過相同原理造成的性功能障礙。[120]
安非他酮,一種弱去甲腎上腺素-多巴胺再吸收抑制劑和尼古丁乙酰膽鹼受體拮抗劑,可能可以用於治療由SSRI類藥物造成的性衝動減退。[121]
體重變化
[編輯]使用抗抑鬱藥時,食慾或體重的變化經常出現,但與藥品種類及藥品影響的神經遞質有關。米氮平與帕羅西汀可能導致食慾、體重增加,[122][123][124]而其它藥物(如安非他酮、文拉法辛)會有相反的效果。[125][126]
有證據顯示,某些三環類、四環類藥物導致食慾、體重增加的效應一定程度上與其抗組胺特性有關。
停藥症候群
[編輯]抗抑鬱藥停藥帶來的症狀最早於1950年代後期首種三環類藥物丙咪嗪的使用中出現。每種新型抗抑鬱藥(包括MAOI類、SSRI類、SNRI類藥物)的出現都帶來了相似的症狀報告。截止2001年,至少有21種不同的抗抑鬱藥(覆蓋所有主要抗抑鬱藥類型)被報道能夠造成停藥症候群。[127]對這個問題的研究並不充分,多數文獻屬於案例報告或是小規模臨床試驗,發生率難以確定、充滿爭議。[127]
停藥症候群患者大多在持續服用抗抑鬱藥四周或更長時間之後突然或快速停藥。[128]常見症狀包括:流感樣症狀(噁心、嘔吐、腹瀉、頭痛、出汗),睡眠不穩(失眠、噩夢、嗜睡),感覺、運動功能異常(失去平衡、顫抖、眩暈、頭暈、類似電擊的感覺),情緒擾動(煩躁不安、焦慮、激動)和認知障礙(迷惑、過度興奮)。[128][129][130]已報告多於50種症狀。[131]
大多數停藥症候群病程持續一至四周,多較輕微並可自行康復;在罕見情況下病情可能較為嚴重、病程也可能延長。[128]帕羅西汀和文拉法辛似乎最難停藥,最長有持續18個月的病程見於報道。[127][132][133]
隨着1980到1990年代SSRI類藥物使用量的爆發式增長和對該種藥物興趣的增加(對氟西汀尤其如此),人們對抗抑鬱藥停藥症候群的興趣也越來越強。[134]1990年代後期,一些研究員認為抗抑鬱藥停藥後出現的症狀可能表明抗抑鬱藥有成癮性,並用「戒斷反應」一詞來描述這些症狀。具有成癮性的物質可造成生理依賴,導致停藥過程較為痛苦。但因服用抗抑鬱藥的患者沒有表現出覓藥行為,這些理論最後都被拋棄了。「戒斷反應」一詞不再用於描述抗抑鬱藥停藥症候群,以避免與藥物成癮造成的現象混淆。[128][135][136]抗抑鬱藥被濫用的情況有時見諸報道,但較為罕見且多發生於那些具有興奮效果的藥物和原先就患有物質使用障礙的人群中。[137]2012年,一項將苯二氮卓和SSRI類藥物停藥反應進行比較的研究認為,因為兩種藥物停藥後症狀相似,沒有理由認為苯二氮類藥物有成癮性而SSRI類藥物沒有。[138]對該研究的回應則表示,沒有證據表明停用SSRI類藥物的患者有覓藥行為,而對於服用苯二氮類藥物的患者則有相關證據,因此應該重新考慮藥品的分類。[139][140]
情感遲鈍
[編輯]抗抑鬱藥可能造成情感遲鈍或麻木的現象。情感遲鈍指的是情感正面與負面兩個極端的減退。病人可能感覺抑鬱有所緩解,但他們在某些情況下也會感受到更少的快樂、共情。要應對這種情況,可以減少藥量、更換藥品。這一現象的發生機制尚不明確。[141][142]
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