How do antidepressants work? - Neil R. Jeyasingam

譯者: Camila Lin 審譯者: Amanda Zhu

In the 1950s, the discovery of two new drugs

在 1950 年代，兩種新藥的問世，

sparked what would become a multibillion dollar market for antidepressants.

開啟了抗憂鬱藥物市場 直至今日高達數十億美元的商機，

Neither drug was intended to treat depression at all—

但它們卻不是為了治療憂鬱症而誕生。

in fact, at the time, many doctors and scientists believed psychotherapy

事實上，當時許多醫生與科學家

都堅信心理治療是憂鬱症的唯一療法。

was the only approach to treating depression.

The decades-long journey of discovery that followed

接下來數十年的發現之旅，

revolutionized our understanding of depression—

讓我們對憂鬱症全面改觀，

and raised questions we hadn’t considered before.

也促使我們思考 之前未曾想過的一些問題。

One of those first two antidepressant drugs was ipronaizid,

第一種抗憂鬱劑「異菸鹼異丙醯肼」，

which was intended to treat tuberculosis.

一開始是結核病的治療藥物。

In a 1952 trial, it not only treated tuberculosis,

但在 1952 年的人體試驗中， 它不只對結核病有療效，

it also improved the moods of patients

受試者中被診斷出患有憂鬱症者，

who had previously been diagnosed with depression.

其情緒也獲得改善。

In 1956, a Swiss clinician observed a similar effect when running a trial

1956 年，一位瑞士的臨床醫師

在臨床測試名為「妥富腦」 的抗過敏藥物時，也發現相似狀況。

for imipramine, a drug for allergic reactions.

Both drugs affected a class of neurotransmitters called monoamines.

這兩種藥都對單胺類的 神經傳導物質產生影響。

The discovery of these antidepressant drugs

這些抗憂鬱藥物的發現

gave rise to the chemical imbalance theory,

促使腦內化學物質失衡理論的誕生，

the idea that depression is caused by having insufficient monoamines

這個理論認為，大腦神經突觸 缺乏單胺類神經傳導物質，

in the brain’s synapses.

就是憂鬱症的成因。

Ipronaizid, imipramine, and other drugs like them

人們認為「異菸鹼異丙醯肼」、 「妥富腦」及其他類似藥物

were thought to restore that balance

可以增加大腦中可用的單胺傳導物質，

by increasing the availability of monoamines in the brain.

進而改善濃度平衡。

These drugs targeted several different monoamines,

這些藥物能夠增加數種 單胺類神經傳導物質，

each of which acted on a wide range of receptors in the brain.

每種傳導物質都會作用於 多種大腦中的受器，

This often meant a lot of side effects,

這代表它們常引起許多副作用，

including headaches, grogginess, and cognitive impairments

包括頭痛、眩暈，與多種認知障礙，

including difficulty with memory, thinking, and judgment.

如記憶力降低，思考困難， 還有判斷力失準。

Hoping to make the drugs more targeted and reduce side effects,

為使藥物療效更精準及減輕副作用，

scientists began studying existing antidepressants

科學家開始研究現有的抗憂鬱藥物，

to figure out which specific monoamines were most associated

以了解究竟哪種單胺類神經傳導物質

with improvements in depression.

是治療憂鬱症的關鍵。

In the 1970s, several different researchers converged on an answer:

1970 年代，多位研究者 都得到一樣的結論：

the most effective antidepressants all seemed to act on one monoamine

最有效的抗憂鬱劑都作用在

「血清素」這種單胺類神經傳導物質。

called serotonin.

This discovery led to the production of fluoxetine, or Prozac, in 1988.

這個發現，促使「氟西汀」 在 1988 年誕生，

它又被稱為「百憂解」， 屬於全新的一類藥物，

It was the first of a new class of drugs

called Selective Serotonin Reuptake Inhibitors, or SSRI’s,

統稱為「選擇性血清素回收抑制劑」，

或稱 SSRI。

which block the reabsorption of serotonin, leaving more available in the brain.

這類藥物可抑制血清素被再吸收， 讓大腦有更多可用的血清素。

Prozac worked well and had fewer side effects

相較於傳統那些 療效不精準的抗憂鬱劑，

than older, less targeted antidepressants.

百憂解療效更好，副作用也更少。

The makers of Prozac also worked to market the drug

百憂解的製造商為了推銷自家藥物， ［憂鬱症很危險］

by raising awareness of the dangers of depression

也對大眾跟醫界宣導 ［憂鬱症不是你能控制的］

to both the public and the medical community.

憂鬱症的危害。 [生病不是你的錯]

More people came to see depression as a disease

因此有越來越多人 將憂鬱症視為一種疾病，

caused by mechanisms beyond an individual’s control,

一種因個人無法控制的機制產生的病， ［責怪、汙名］

which reduced the culture of blame and stigmatization surrounding depression,

這個認知削弱了對憂鬱症患者 的責怪力道，洗刷憂鬱症的汙名，

and more people sought help.

也讓更多患者願意尋求幫助。

In the 1990s, the number of people being treated for depression skyrocketed.

1990 年代，接受治療的 患者數大幅提升，

Psychotherapy and other treatments fell by the wayside,

接受心理治療與其他療法 的人數則大幅減少，

and most people were treated solely with antidepressant drugs.

因為大多數的病人 僅用抗憂鬱劑治療憂鬱症。

Since then, we’ve developed a more nuanced view of how to treat depression—

從那時開始，我們對如何治療憂鬱症 及憂鬱症的成因，

and of what causes it.

有了更細緻入微的認知。

Not everyone with depression responds to SSRIs like Prozac—

但不是所有患者都對百憂解等 SSRI 反應良好，

some respond better to drugs that act on other neurotransmitters,

有些人更適合使用 針對其他神經傳導物的藥物，

or don't respond to medication at all.

也有對藥物毫無反應的人。

For many, a combination of psychotherapy and antidepressant drugs

對很多人來說， 結合心理治療與藥物的療法，

is more effective than either alone.

比單仰賴其中一種的效果更好。

We’re also not sure why antidepressants work the way they do:

我們也不太清楚 抗憂鬱劑產生療效的原理：

they change monoamine levels within a few hours of taking the medication,

服藥後的數小時內， 單胺類神經傳導物質的濃度就已改變，

but patients usually don’t feel the benefit until weeks later.

但卻要等到數個禮拜後， 患者才會感受到療效。

And after they stop taking antidepressants,

如果患者停藥，

some patients never experience depression again, while others relapse.

有些人會完全痊癒， 有些人卻會再度發病。

We now recognize that we don’t know what causes depression,

我們現在所理解的， 就是我們不清楚憂鬱症的成因，

or why anti-depressants work.

也不清楚抗憂鬱藥物為什麼有效。

The chemical imbalance theory is at best an incomplete explanation.

「腦內化學物質失衡理論」 仍無法提供完整的解釋。

It can’t be a coincidence that almost all the antidepressants

幾乎所有抗憂鬱劑都作用於血清素，

happen to act on serotonin,

絕不是個巧合，

but that doesn’t mean serotonin deficiency is the cause of depression.

但這也不代表， 血清素不足就會導致憂鬱症。

If that sounds odd, consider a more straightforward example:

如果這聽起來很怪， 請想想一個更直接的例子：

steroid creams can treat rashes caused by poison ivy—

類固醇藥膏能治療野葛導致的紅疹，

the fact that they work doesn’t mean steroid deficiency

類固醇有藥效，

不代表類固醇不足 就是疹子產生的原因。

was the cause of the rash.

We still have a ways to go in terms of understanding this disease.

在認識憂鬱症這件事上， 我們還有很長一段路要走。

Fortunately, in the meantime, we have effective tools to treat it.

幸運的是，我們已經有 許多有效的抗憂鬱療法了。