How do antidepressants work? - Neil R. Jeyasingam

翻译人员: Wanting Zhong 校对人员: Yanyan Hong

In the 1950s, the discovery of two new drugs

在 20 世纪 50 年代， 两种新药的发现

sparked what would become a multibillion dollar market for antidepressants.

激发了日后价值数十亿美元的 抗抑郁药市场。

Neither drug was intended to treat depression at all—

原来这两种药根本没有打算 用来治疗抑郁症——

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

事实上，当时许多医生和科学家都相信

心理治疗是医治抑郁症的唯一方法。

was the only approach to treating depression.

The decades-long journey of discovery that followed

随后长达数十年的探索之旅

revolutionized our understanding of depression—

彻底改变了我们对抑郁症的理解——

and raised questions we hadn’t considered before.

并提出了我们未曾思考过的问题。

One of those first two antidepressant drugs was ipronaizid,

异烟酰异丙肼（Iproniazid） 是最早的两种抗抑郁药之一，

which was intended to treat tuberculosis.

最初打算用来治疗结核病。

In a 1952 trial, it not only treated tuberculosis,

在 1952 年的一次试验中， 它不仅治好了结核病，

it also improved the moods of patients

还改善了抑郁症患者的情绪。

who had previously been diagnosed with depression.

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

1956 年，一名瑞士临床医生

在对一种过敏药 丙咪嗪（imipramine）进行试验时

for imipramine, a drug for allergic reactions.

发现了类似的效果。

Both drugs affected a class of neurotransmitters called monoamines.

这两种药物都能影响 一种叫做单胺类的神经递质。

The discovery of these antidepressant drugs

这些抗抑郁药物的发现

gave rise to the chemical imbalance theory,

催生了 “化学物不平衡理论”，

the idea that depression is caused by having insufficient monoamines

认为抑郁症是由于大脑的突触里

缺乏足够的单胺类递质而造成的。

in the brain’s synapses.

Ipronaizid, imipramine, and other drugs like them

异烟酰异丙肼、丙咪嗪和其它类似药物

were thought to restore that balance

能通过增加大脑内单胺类递质的供应

by increasing the availability of monoamines in the brain.

而恢复这个平衡。

These drugs targeted several different monoamines,

这些药物能针对 几种不同的单胺类递质，

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

每种递质都能广泛作用于 大脑里的各种受体。

This often meant a lot of side effects,

这通常意味着很多副作用，

including headaches, grogginess, and cognitive impairments

包括头痛、头晕，

以及记忆、思考和判断困难 等认知障碍。

including difficulty with memory, thinking, and judgment.

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

为了让药物更具针对性、减少副作用，

scientists began studying existing antidepressants

科学家们开始研究现有的抗抑郁药，

to figure out which specific monoamines were most associated

想要找出哪些特定的单胺类递质

和抑郁症的改善最为密切相关。

with improvements in depression.

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

在 20 世纪 70 年代， 几位研究者得出了一致的答案：

the most effective antidepressants all seemed to act on one monoamine

最有效的抗抑郁药物似乎都作用于

一种叫做血清素的单胺类递质。

called serotonin.

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

这一发现使得氟西汀，即百忧解， 于 1988 年问世。

It was the first of a new class of drugs

它是一类新药中的第一个——

called Selective Serotonin Reuptake Inhibitors, or SSRI’s,

这类药物叫做 选择性血清素再摄取抑制剂（SSRI），

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

能阻止对血清素的再摄取， 从而增加大脑中的血清素储备。

Prozac worked well and had fewer side effects

百忧解效果很好，

副作用也少于更早的、 针对性更弱的抗抑郁药。

than older, less targeted antidepressants.

The makers of Prozac also worked to market the drug

为了推销这种药， 百忧解的生产商也致力于

by raising awareness of the dangers of depression

提升公众和医疗群体 对抑郁症危害的意识。

to both the public and the medical community.

More people came to see depression as a disease

更多人开始将抑郁症视为一种疾病，

caused by mechanisms beyond an individual’s control,

其发病机制不受个人控制，

which reduced the culture of blame and stigmatization surrounding depression,

从而减少了围绕抑郁症的 责备与污名化，

and more people sought help.

也让越来越多人去寻求帮助。

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

20 世纪 90 年代， 接受抑郁症治疗的人数迅速飞升。

Psychotherapy and other treatments fell by the wayside,

心理治疗和其它疗法纷纷旁落，

and most people were treated solely with antidepressant drugs.

大多数人只使用抗抑郁药物进行治疗。

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

从那之后，我们对抑郁症疗法 和抑郁症成因的看法

and of what causes it.

变得更加慎重细致。

Not everyone with depression responds to SSRIs like Prozac—

百忧解等 SSRI 药物并不是 对每一位抑郁症患者都有效果——

some respond better to drugs that act on other neurotransmitters,

作用于其他神经递质的药物 对有些人效果更好，

or don't respond to medication at all.

有些人甚至任何药物都对他们无效。

For many, a combination of psychotherapy and antidepressant drugs

对于很多人来说， 心理治疗和抗抑郁药相结合

is more effective than either alone.

比单独使用一种疗法更为有效。

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

我们也不清楚抗抑郁药为何如此作用：

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

它们在服药后几小时内 就能改变单胺类浓度，

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

但患者通常要等到几个星期后 才能感受到效益。

And after they stop taking antidepressants,

而在他们停止服用抗抑郁药后，

some patients never experience depression again, while others relapse.

有的患者再也不会经历抑郁症， 而有人却会复发。

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

我们现在认识到， 我们不知道抑郁症的成因，

or why anti-depressants work.

也不知道抗抑郁药的原理。

The chemical imbalance theory is at best an incomplete explanation.

化学物不平衡理论 最多是一个不完整的解释。

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

几乎所有抗抑郁药 都恰好作用于血清素，

happen to act on serotonin,

这不可能是巧合，

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

但也不意味着缺乏血清素 就是抑郁症的成因。

If that sounds odd, consider a more straightforward example:

如果这听起来很奇怪， 那就想象一个更直接的例子：

steroid creams can treat rashes caused by poison ivy—

类固醇软膏可用于治疗 毒漆藤引起的皮疹——

the fact that they work doesn’t mean steroid deficiency

但类固醇有效的事实并不代表

was the cause of the rash.

类固醇缺乏是皮疹的原因。

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

在理解抑郁症这一方面， 我们还有很长的路要走。

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

所幸的是，在此期间， 我们有治疗它的有效工具。