Opinion
Diagnosing the Wrong Deficit
May 18, 2013
觀點
被誤診的睡眠失調
瓦察爾·G·塔卡爾 2013年05月18日
Shannon Freshwater
2010年春，一名新患者來找我看病，看他是否患有注意力
缺陷多動障礙（Attention Deficit Hyperactivity
Disorder，簡稱ADHD）。他表現出所有的典型癥狀：拖延、健忘、習慣性地丟三落四，當然還有不能持續保持注意力的問題。但有一個不同尋常的地
方。他的這些癥狀兩年前才出現，當時他已31歲。
雖然我看過不少ADHD的成年患者，但這一病例還是有違一項重要的診斷標準：癥狀必須在兒童時期就出現了。其實是這樣，他首次開始出現這些癥狀是在他換了新工作的那個月，新工作需要他早上5點起床，而他是個有夜貓子習慣的人。
- 檢視大圖
Shannon Freshwater
我發現，他患的不是ADHD，而是長期睡眠不足。我向他推
薦了一些有助於他在晚上入睡的技巧，比如在10點上床之前放鬆90分鐘。如有必要，他可以服用小劑量的褪黑素。當他在兩周後再來看病時，他的癥狀幾乎完全
消失了。我建議他如果癥狀複發，就給我打電話，但我再也沒有接到過他的電話。
人們拋出各種理論來解釋為什麼被診斷為患有ADHD並因此
接受治療的兒童和成人人數上升。根據美國疾病控制與預防中心(Centers for Disease Control and
Prevention)的數據，如今有11%的學齡兒童被診斷為ADHD患者。我不懷疑很多人確實患有ADHD；我經常確診並治療成人患者。但是，假如相
當一部分的病例實際上是被誤診的睡眠障礙，結果會怎樣呢？
對一些人、特別是兒童來說，睡眠不足不一定會讓他們無精打采；相反，他們會變得多動且無法集中注意力。研究人員和記者越來越多地注意到，睡眠失調與看似ADHD的癥狀之間存在聯繫，但這些聯繫是很長時間後才被父母和醫生了解清楚的。
我們如今都比過去睡得少。稱每晚睡眠少於7小時的成人數從
1960年的大約2%上升到2011年的35%。睡眠對兒童來說尤為重要，兒童需要慢波睡眠——深沉的、恢復活力的那種慢波睡眠——才能良好成長和發育。
但如今的年輕人比100年前的年輕人每天少睡一個多小時。對所有年齡的人來說，現代的日間活動，以馬不停蹄的14小時日程表和難以避免的對褪黑素有抑制作
用的蘋果設備為標誌，這類活動往往會削弱睡眠。這也許只是巧合，這種限制睡眠的生活方式從上世紀90年代開始越來越走向極端，而那個年代也是診斷ADHD
病例爆發的10年。
一些研究表明，被診斷為ADHD的兒童中有很大一部分也有睡眠障礙性呼吸，如呼吸暫停或打鼾、不寧腿綜合征，或非恢復性睡眠，指的是慢波睡眠不時被打斷。
一項2004年發表在《睡眠》(Sleep)期刊的研究，對34名ADHD患兒做了觀察，所有患兒都表現出缺乏慢波睡眠，而對照組的32個兒童中，只有少數人表現了缺乏慢波睡眠。
一項2006年發表在《小兒科》(Pediatrics)
期刊的研究，從外科臨床的角度，發現了類似的情況。該研究包括105名年齡在5歲到12歲之間的兒童。他們中有78人因有睡眠呼吸障礙而做了切除扁桃體手
術，其餘27人則作為對照組接受其他手術。研究人員觀察了參與者的睡眠模式，並檢測其多動和不專心的程度，他們用的方法與驗證ADHD診斷的標準方法一
致。
在接受扁桃體切除術的78名兒童中，28%的兒童被確診患有ADHD，而得到這個診斷的在對照組中只有7%。
研究者們在這些兒童接受手術一年後對他們進行了回訪，其發現更令人震驚。最初的ADHD患者，在做了扁桃體切除術後，有整整一半——22人中的11人——不再符合ADHD的確診標準。換言之，最初看似ADHD的癥狀通過治療睡眠問題而消失了。
但另外一種情況也是可能的，與ADHD相似的癥狀在解決了
睡眠問題後繼續存在。讓我們來看看去年發表在《小兒科》期刊上的一項針對1.1萬多個英國兒童的長期研究。研究人員在嬰兒只有半歲大時詢問他們的母親，嬰
兒是否有睡眠障礙性呼吸。接下來，在這些孩子四歲和七歲時，他們的母親完成了一份行為問卷，評測其孩子不專心、多動、焦慮、抑鬱的程度，以及和同齡人相
處、行為和社會技能等。
研究發現，在嬰兒時期有睡眠障礙性呼吸的兒童，更可能在今
後的生活中表現出行為問題，四歲時他們表現出行為問題的可能性增加20%到60%，到七歲時則增加40%到100%。有意思的是，即使障礙性呼吸得到緩
解，他們還會表現出行為問題，這意味着嬰兒時期的呼吸障礙可能會造成某種潛在的不可逆神經損傷。
很明顯，在兒童的夜間生命中有比我們所了解的多得多的事情。但通常我們只能看到和診斷出他們後來的日間癥狀。
對童年期後的睡眠和ADHD所進行的研究比較少。但還是有個獨一無二的這類研究，來自馬薩諸塞州總醫院(Massachusetts General Hospital)的一個團隊發現，ADHD成年患者的睡眠失調癥狀與ADHD患兒的睡眠失調癥狀非常相似。
也有一些正在做的針對成人睡眠的很有前景的研究，研究針對
注意力、記憶力和認知表現。一項發表在2月份的《自然神經科學》(Nature
Neuroscience)期刊上的研究發現，老年人的慢波睡眠量與其在記憶測試中的表現有關聯。三年前發表在《睡眠》期刊上的一項研究發現，雖然睡眠不
足的研究對象不一定會自我報告感到更睏乏，但其認知下降的程度與睡眠不足成正比，在連續五個夜晚睡眠受限制後，他們的認知表現進一步持續惡化。
其實，《精神疾病診斷與統計手冊》(Diagnostic
and Statistical Manual of Mental
Disorders)曾將「在睡眠中過度活動」列為注意力缺陷障礙的癥狀。那本出版於1980年的《手冊》，首次為這一障礙命名。增加了「多動」的
ADHD名稱出現在1987年，那以後，ADHD的診斷標準中不再包括睡眠問題。手冊作者表示，沒有足夠證據支持繼續把睡眠問題納入診斷標準中。
但是，如果醫生在對病人作出ADHD診斷前，的確需要先尋
找睡眠失調的證據，又會怎樣呢？通常，精神疾病研究者不具有診斷睡眠問題的設備或者這方面的專業知識。讓病人自己記錄睡眠日記有點困難，讓他們去做昂貴的
整夜睡眠診斷也不容易，這需要使用複雜的設備，比如需要將表面電極貼在患者身上，以測量大腦和肌肉活動；讓他們戴上腹帶以記錄呼吸；還要用「脈搏血氧儀」
測量血氧飽和度；甚至還需要用鼾聲探測器。（也不能保證保險公司會同意支付睡眠診斷的費用。）而目前，ADHD只需通過一次辦公室里的面談就可以做出診
斷。
有時，我的病人對我提出他們做睡眠測試的建議有抵觸情緒，
因為他們看到的所有信息都宣稱ADHD是罪魁禍首，這些信息往往是藥品公司直接針對消費者做的銷售宣傳。人們不喜歡聽到自己可能患有另一種聽上去更怪，而
且不能靠服藥就能控制的疾病；然而，這種情況在病人看到自己的睡眠診斷結果後通常會改變。
除了專業興趣，我對ADHD和睡眠失調還有個人興趣。我從大學時代開始，有近10年的時間受嚴重的認知遲鈍和集中注意力困難等問題困擾，有每天打盹的習慣，而且周末嗜睡。我之所以能通過醫學院的考試，靠的是出色的記憶技巧，還靠了麻黃屬植物，那時這類增補品還是合法的。
我曾被誤診患有各種疾病，包括ADHD。後來我做了兩次睡
眠診斷，最終被發現患有非典型性嗜眠發作。這很讓我吃驚，因為我從來沒有過在吃飯或講話時睡着的經歷。但事實上，我夜裡睡眠時間的40%以上，是快速眼球
運動（Rapid Eye
Movement，簡稱REM）睡眠，也就是「做夢睡眠」，而正常情況下這種睡眠在夜裡只應間歇性出現，我只有5%的時間是處於具有修復功能的慢波睡眠
中。我每天晚上睡8到10個小時，但仍然患有嚴重的慢波睡眠缺乏症。
經過反覆嘗試之後，終於找到了正確的治療方法，我的認知問
題得到了改善。現在我吃得好，而且順應自己獨特的睡眠需要，而不是試圖抑制這種需求。我還服用兩種葯：一種是針對嗜眠發作的興奮劑，另一種是SNRI，睡
前服用；SNRI全稱血清素-去甲腎上腺素重攝取抑制劑(serotonin-norepinephrine reuptake
inhibitor)，是一種抗抑鬱劑，這是該葯未被批准的一種用法，可以抑制REM睡眠並幫助延長慢波睡眠。現在我可以不使用鬧鐘就能起床，我白天的注
意力也大為提高。我恢復得不錯（雖然我妻子會說，周末的早上我依然不行，照顧我們的兩個孩子全靠她了。）
注意力缺陷問題遠遠不是我們需要重視缺少高質量睡眠的唯一原因。實驗室里的動物被剝奪慢波睡眠後會死亡。長期的慢波睡眠缺乏與人類的很多疾病有關聯，包括抑鬱症、心臟病、高血壓、肥胖症、慢性疼痛、糖尿病，以及癌症，更不用提每年成千上萬的與疲勞有關的車禍了。
睡眠失調如此常見，所有的內科醫生、兒科醫生、精神科醫生都應該對其常規性排查。我們需要更多的睡眠失調研究。每年，好幾十億美元的錢花在研究癌症、抑鬱症和心臟病上，但有多少錢用於睡眠研究呢？
今年，國立衛生研究院(The National Institutes of Health)在睡眠研究上僅投入2.4億美元。有這樣一個問題，研究項目的設置各自為政，撥給心臟病或精神病研究的錢，極少會被用到睡眠醫學這類其他領域，即使這些疾病密切相關。
但是，我們對慢波睡眠與ADHD關係的關注不能再等待了。
如果你還沒被說服的話，想想可樂寧(clonidine)這個藥物吧。可樂寧最初是治療高血壓的，後來得到食品和藥物管理局
(Food and Drug Administration)的許可，用於治療ADHD。研究顯示，如果只在睡前服用可樂寧，也能改善白天的癥狀。對於
精神病學家來說，這是那種「哦，我們不知道它如何起作用的」藥物之一。但是，讓我告訴你一個鮮為人知事實：可樂寧對改善慢波睡眠可能很有效。
瓦察爾·G·塔卡爾(Vatsal G. Thakkar)是紐約大學醫學院的臨床助理教授。本文最初發表於2013年4月28日。
翻譯：陶夢縈、張亮亮、梁英
IN the spring of 2010, a new patient came to see me
to find out if he had attention-deficit hyperactivity disorder. He had
all the classic symptoms: procrastination, forgetfulness, a propensity
to lose things and, of course, the inability to pay attention
consistently. But one thing was unusual. His symptoms had started only
two years earlier, when he was 31.
Though I treat a lot of
adults for attention-deficit hyperactivity disorder, the presentation of
this case was a violation of an important diagnostic criterion:
symptoms must date back to childhood. It turned out he first started
having these problems the month he began his most recent job, one that
required him to rise at 5 a.m., despite the fact that he was a night
owl.
The patient didn’t have A.D.H.D., I realized, but a
chronic sleep deficit. I suggested some techniques to help him fall
asleep at night, like relaxing for 90 minutes before getting in bed at
10 p.m. If necessary, he could take a small amount of melatonin. When he
returned to see me two weeks later, his symptoms were almost gone. I
suggested he call if they recurred. I never heard from him again.
Many theories are thrown
around to explain the rise in the diagnosis and treatment of A.D.H.D. in
children and adults. According to the Centers for Disease Control and
Prevention, 11 percent of school-age children have now received a
diagnosis of the condition. I don’t doubt that many people do, in fact,
have A.D.H.D.; I regularly diagnose and treat it in adults. But what if a
substantial proportion of cases are really sleep disorders in disguise?
For some people —
especially children — sleep deprivation does not necessarily cause
lethargy; instead they become hyperactive and unfocused. Researchers and
reporters are increasingly seeing connections between dysfunctional
sleep and what looks like A.D.H.D., but those links are taking a long
time to be understood by parents and doctors.
We all get less sleep than
we used to. The number of adults who reported sleeping fewer than seven
hours each night went from some 2 percent in 1960 to more than 35
percent in 2011. Sleep is even more crucial for children, who need delta
sleep — the deep, rejuvenating, slow-wave kind — for proper growth and
development. Yet today’s youngsters sleep more than an hour less than
they did a hundred years ago. And for all ages, contemporary daytime
activities — marked by nonstop 14-hour schedules and inescapable melatonin-inhibiting iDevices
— often impair sleep. It might just be a coincidence, but this
sleep-restricting lifestyle began getting more extreme in the 1990s, the
decade with the explosion in A.D.H.D. diagnoses.
A number of studies have
shown that a huge proportion of children with an A.D.H.D. diagnosis also
have sleep-disordered breathing like apnea or snoring, restless leg
syndrome or non-restorative sleep, in which delta sleep is frequently
interrupted.
One study, published in
2004 in the journal Sleep, looked at 34 children with A.D.H.D. Every one
of them showed a deficit of delta sleep, compared with only a handful
of the 32 control subjects.
A 2006 study in the journal
Pediatrics showed something similar, from the perspective of a surgery
clinic. This study included 105 children between ages 5 and 12.
Seventy-eight of them were scheduled to have their tonsils removed
because they had problems breathing in their sleep, while 27 children
scheduled for other operations served as a control group. Researchers
measured the participants’ sleep patterns and tested for hyperactivity
and inattentiveness, consistent with standard protocols for validating
an A.D.H.D. diagnosis.
Of the 78 children getting
the tonsillectomies, 28 percent were found to have A.D.H.D., compared
with only 7 percent of the control group.
Even more stunning was what
the study’s authors found a year after the surgeries, when they
followed up with the children. A full half of the original A.D.H.D.
group who received tonsillectomies — 11 of 22 children — no longer met
the criteria for the condition. In other words, what had appeared to be
A.D.H.D. had been resolved by treating a sleeping problem.
But it’s also possible that
A.D.H.D.-like symptoms can persist even after a sleeping problem is
resolved. Consider a long-term study of more than 11,000 children in
Britain published last year, also in Pediatrics. Mothers were asked
about symptoms of sleep-disordered breathing in their infants when they
were 6 months old. Then, when the children were 4 and 7 years old, the
mothers completed a behavioral questionnaire to gauge their children’s
levels of inattention, hyperactivity, anxiety, depression and problems
with peers, conduct and social skills.
The study found that
children who suffered from sleep-disordered breathing in infancy were
more likely to have behavioral difficulties later in life — they were 20
to 60 percent more likely to have behavioral problems at age 4, and 40
to 100 percent more likely to have such problems at age 7.
Interestingly, these problems occurred even if the disordered breathing
had abated, implying that an infant breathing problem might cause some
kind of potentially irreversible neurological injury.
CLEARLY there is more going
on in the nocturnal lives of our children than any of us have realized.
Typically, we see and diagnose only their downstream, daytime symptoms.
There has been less
research into sleep and A.D.H.D. outside of childhood. But a team from
Massachusetts General Hospital found, in one of the only studies of its
kind, that sleep dysfunction in adults with A.D.H.D. closely mimics the
sleep dysfunction in children with A.D.H.D.
There is also some
promising research being done on sleep in adults, relating to focus,
memory and cognitive performance. A study published in February in the
journal Nature Neuroscience found that the amount of delta sleep in
seniors correlates with performance on memory tests. And a study
published three years ago in Sleep found that while subjects who were
deprived of sleep didn’t necessarily report feeling sleepier, their
cognitive performance declined in proportion to their sleep deprivation
and continued to worsen over five nights of sleep restriction.
As it happens, “moves about
excessively during sleep” was once listed as a symptom of
attention-deficit disorder in the Diagnostic and Statistical Manual of
Mental Disorders. That version of the manual, published in 1980, was the
first to name the disorder. When the term A.D.H.D., reflecting the
addition of hyperactivity, appeared in 1987, the diagnostic criteria no
longer included trouble sleeping. The authors said there was not enough
evidence to support keeping it in.
But what if doctors, before
diagnosing A.D.H.D. in their patients, did have to find evidence of a
sleep disorder? Psychiatric researchers typically don’t have access to
the equipment or expertise needed to evaluate sleep issues. It’s tricky
to ask patients to keep sleep logs or to send them for expensive
overnight sleep studies, which can involve complicated equipment like
surface electrodes to measure brain and muscle activity; abdominal belts
to record breathing; “pulse oximeters” to measure blood oxygen levels;
even snore microphones. (And getting a sleep study approved by an
insurance company is by no means guaranteed.) As it stands, A.D.H.D. can
be diagnosed with only an office interview.
Sometimes my patients have
resisted my referrals for sleep testing, since everything they have read
(often through direct-to-consumer marketing by drug companies)
identifies A.D.H.D. as the culprit. People don’t like to hear that they
may have a different, stranger-sounding problem that can’t be fixed with
a pill — though this often changes once patients see the results of
their sleep studies.
Beyond my day job, I have a
personal interest in A.D.H.D. and sleep disorders. Beginning in college
and for nearly a decade, I struggled with profound cognitive lethargy
and difficulty focusing, a daily nap habit and weekend sleep addiction. I
got through my medical school exams only by the grace of good
memorization skills and the fact that ephedra was still a legal
supplement.
I was misdiagnosed with
various maladies, including A.D.H.D. Then I underwent two sleep studies
and, finally, was found to have an atypical form of narcolepsy. This was
a shock to me, because I had never fallen asleep while eating or
talking. But, it turned out, over 40 percent of my night was spent in
REM sleep — or “dreaming sleep,” which normally occurs only
intermittently throughout the night — while just 5 percent was spent in
delta sleep, the rejuvenating kind. I was sleeping 8 to 10 hours a
night, but I still had a profound delta sleep deficit.
It took some trial and
error, but with the proper treatment, my cognitive problems came to an
end. Today I eat well and respect my unique sleep needs instead of
trying to suppress them. I also take two medications: a stimulant for
narcolepsy and, at bedtime, an S.N.R.I. (or serotonin-norepinephrine
reuptake inhibitor) antidepressant — an off-label treatment that
curtails REM sleep and helps increase delta sleep. Now I wake up without
an alarm, and my daytime focus is remarkably improved. My recovery has
been amazing (though my wife would argue that weekend mornings are still
tough — she picks up the slack with our two kids).
Attention-deficit problems
are far from the only reasons to take our lack of quality sleep
seriously. Laboratory animals die when they are deprived of delta sleep.
Chronic delta sleep deficits in humans are implicated in many diseases,
including depression, heart disease, hypertension, obesity, chronic
pain, diabetes and cancer, not to mention thousands of fatigue-related
car accidents each year.
Sleep disorders are so
prevalent that every internist, pediatrician and psychiatrist should
routinely screen for them. And we need far more research into this
issue. Every year billions of dollars are poured into researching
cancer, depression and heart disease, but how much money goes into
sleep?
The National Institutes of
Health will spend only $240 million on sleep research this year. One of
the problems is that the research establishment exists as mini-fiefdoms —
money given to one sector, like cardiology or psychiatry, rarely makes
it into another, like sleep medicine, even if they are intimately
connected.
But we can’t wait any
longer to pay attention to the connection between delta sleep and
A.D.H.D. If you’re not already convinced, consider the drug clonidine.
It started life as a hypertension treatment, but has been approved by
the Food and Drug Administration to treat A.D.H.D. Studies show that
when it is taken only at bedtime, symptoms improve during the day. For
psychiatrists, it is one of these “oh-we-don’t-know-how-it-works” drugs.
But here is a little-known fact about clonidine: it can be a potent
delta sleep enhancer.
Vatsal G. Thakkar is a clinical assistant professor of psychiatry at the N.Y.U. School of Medicine.
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