She tried to laugh it off and gave explanation about being really exhausted from playing golf and being up all night with my stepfather who has his own set of health problems and corresponding addictions. There was no rush, no timetable. The wisdom that comes from watching others live with humiliating losses in quality of life as they suffer increasing and intractable pain has convinced me that I was wrong. Die , Defeated , Nothing. If I could pin down what is causing this it would help.
My family is really bugging me to get off of it, but it is the only relief I get as far as sleep. They keep sending me emails and articles that state that ambien will shorten your lifespan and the medical dangers of it. I sometimes try to wean down to 5 mg. Is there really any adverse effects medically for taking ambien long term? From a brief query at PubMed a government database of medical articles , I found this study from Using hypnotics like Ambien 30 times per month is associated with a similar mortality hazard to smoking packs of cigarettes per day.
In spite of feeling like you are getting sleep, hypnotics actually end up impairing your daytime performance, cognition and memory. Plus, chronic Ambien use can increase the risk of automobile accidents and falls and promote unfavourable changes in personality. What does your prescribing doctor say about using Ambien?
Also, have you looked into some other pharmaceutical or lifestyle alternatives? I have been on Ambien for 8 years now. It helps me sleep and I wake up feeling rested and ready for my day. I have had no problems and sleep like a baby! And you can consult some national sleep associations and see what their opinion about Ambien is. Have you spoken with your doctor about alternatives to sleep aids? Also, if you have great responsibility in your life, what are you doing to manage the anxiety?
This might be something to look into, which can help change your life. My wonderful physician husband who also plays music in his spare time of 22 years we had been together 25 was prescribed Ambien about 11 years ago by a sleep specialist. As a doctor, my husband was on call a lot, and had difficulty returning to sleep on the nights he was not on call. Within the first year of using Ambien, he was clearly addicted, and could not sleep without taking it.
Then, he could not sleep even when taking it. Then, he tried taking more. Later, he told me he felt bad all the time. It was as if he had no personality. At night, he would wake up with weird nightmares, shuffle into the kitchen, eat, and then take some more Ambien to try to get back to sleep. Sometimes he would play his guitar at odd hours. At some point, as a scientist, he realized he was addicted and took himself off of it. The withdrawal symptoms were horrific.
The details he related to me included: My two daughters were noticing the changes; but he had always been reserved, and doctors are good at hiding their feelings because they deal with life or death situations. I know that his personality has altered so much—there were times I thought he was exhibiting signs of mental illness. As his wife, I thought perhaps he was unhappy with me so I continued to try to be the perfect wife, mother, and to work hard on my career. He seemed better up until a few years ago.
I did not know at the time that he had resumed his Ambien dosing; using the newer form, which is supposed to act somewhat differently than the previous version of the drug. Now, as he returned to Ambien, his behavior became quite hostile. We went to a counselor who said that he was bordering on the thought patterns of a sociopath.
This once Phi Beta Kappa borderline genius and talented musician, the man who cherished our two children, now covered his arm with tattoos, forgot entire conversations, and alienated some long time friends others just thought it was a mid-life crisis. He purchased hundreds of books on everything from world religions, to the devil, to the history of nudity.
It goes on and on. I am sure there are others—Cocaine, Heroin, Meth—but this one is entirely legal and prescribed daily all over the world. It seems innocuous, but everytime I meet someone who is taking it, I offer my cautionary tale. This is one of the most patient women I have ever known. She and her husband now ex had been in recovery for a few years, but he noticed she started drinking and drugging again when the affair with my husband began. We divorced last year and I moved with my younger child out of state.
My now ex still practices medicine, still puts on the the appearance of a normal person to the outside world. When my mother was dying, he came over and said more strange things. When his mother died this year he said to one of our children, he expressed no emotions. I know that our brains are complex systems; it is possible my former husband suffered from a number of issues. Sometimes brilliant people do. However, I am convinced that Ambien led to or at least contributed to his downfall.
You are wise to consider not taking it, and, if you are taking it now, to seek to reduce and finally eliminate it. If you are seeking restful sleep, I wish you the best, but the madness that this drug can create is much worse. Thank you for sharing about your very difficult time battling with an addicttion to Ambien. I hope that your husband and your story can help others. My doctor prescribed it to me because of ongoing sleep disorders, insomnia being the biggest.
Building tolerance to sleep medications like Ambien quickly is one of the downsides to the efficacy of using Ambien to fall asleep. In other words, the longer you use Ambien, the less effective it can be. Have you considered any other alternatives to Ambien? My beautiful and brilliant mother has been using Ambien, on and off, but mostly on- for several years now. She sleep walks and eats, mixing cocktails and putting things in microwave that have caused small fires.
She has slipped and fallen a few times, and once defecated all over herself and the floor. My family has allowed it to become fodder for funny stories at get-togethers. However, now it seems that all of us having accepted this as funny has created a normalizing of a dangerous situation. My mom has been saying for years that she needs to do something about it, and she has occasionally pursued natural remedies for brief time periods. She also became addicted to Oxycontin for a short time period, and in withdrawal from that, she felt the need to go back on the Ambien.
I wish I could convince my super strong and intelligent mother of the importance of finding healthier options, but when I try to talk to her about how I feel about her drug use, she goes from sweetness to hostility. She tried to laugh it off and gave explanation about being really exhausted from playing golf and being up all night with my stepfather who has his own set of health problems and corresponding addictions. I told her I loved her dearly, but that I was not going to participate in this conversation and hung up the phone.
I feel helpless in the face of this. And yet, I wonder how healthy it is for them to be in an environment where drug addiction is an acceptable norm and fodder for funny stories. One of my talented employees started coming to work impaired. I discovered she had an addiction to xanax and trazadone and she had been stealing from us to support it. I know a lovely young woman who found out she was pregnant, and in the process of trying to wean off of prescription drugs for anxiety, vertigo, and sleep Ambien being one , she miscarried.
He had successfully used yoga practice, massage, and acupuncture to recover from his own addiction to Ambien. And these are just a few…ARGH!!! Accept that sometimes you will feel pain. That is part of being human and alive. There are ways to get healthy, without damaging your liver and kidneys and heart, or devastating your relationships with loved ones. After my children were born, I had a terrible time getting to sleep, and when I did, my sleep quality was so poor, I no longer had a clear distinction between being asleep and awake.
I was so exhausted and sleep-deprived, I was occasionally uncertain as to whether I was dreaming or awake. I was moody and prone to depression. I was offered pharmaceutical options, but the feeling I would get from any narcotic or hypnotic drug was fortunately, I guess so uncomfortable to me that I refused the drugs and did my best to manage with moderate to vigorous daily exercise, cat naps, and journal writing.
Then I was diagnosed with cervical cancer when my youngest child was 4 years old. I chose to participate in a study for a form of treatment that did not require chemotherapy, but did cause intense fatigue. During that treatment, I sought acupuncture therapy to support my adrenals. A couple years later, I was in an accident that resulted in whiplash, a severe concussion, and ultimately a ruptured spinal disc, spinal spasms, and multiple super painful neuropathies.
Instead, I found a wonderful ally, in that he had come to conclusion throughout his years that many standard therapies are causing much greater problems than they are solving. He guided me to a course of treatment that eschewed the AMA standard prednisone, xanax, vicodin for a much gentler approach- Chinese trauma pills which are taken for just a couple days , Xi Gong meditation which I had never done, but found a great teacher easily on the internet , ibuprofrin on a reduction schedule, weekly acupuncture, neuromuscular massage, and marijuana tea before bed.
He recommended the latter for no more than 5 weeks. As it turns out, I took it for 5 days, stopped for a few, did it again for 3 days, and the spasms were gone. I had no desire to continue with that, once the underlying problem was solved, as it did cause dry mouth and eyes. I was back to walking a couple miles each day and a fairly normal yoga practice within 6 weeks of the accident.
It was a time-consuming treatment plan vs. I committed myself to this course of action, knowing that it was critical for my career, my family life, and my social life. Initially, I got acupuncture treatments twice weekly and massage once weekly, and I took an herbal formulation powder made into a tea three times daily.
Within a couple weeks, with no side effects whatsoever, I started to feel some distinction between sleep and wake. The herbal formulation was tweaked every few weeks, and my treatment schedule was reduced over the next few months. My moods are much more stable, much less prone to bouts of depression and anxiety. In gratitude, and to have it all convenient for my own needs ,I opened a studio in my neighborhood that offers yoga, acupuncture, and massage.
Now and again, especially with the pressures related to operating this facility, I have a few rough nights. Sleeping well is such a wonderful thing, and I understand the panic and anxiety people feel when they are not getting that. However, resorting to an addictive substance with dangerous side effects is not the only solution. Good luck out there! I really feel the hurt and concern for your mother in this message. Although you cannot do anything to change an addict who is living in addiction, you can make steps towards accepting what you can change — yourself!
And as difficult a pill as this is to swallow, there is peace inside of yourself. Because in the end, we can only control ourselves. I end up just staring at my ceiling all night. I had hallucinations the first week but those have mostly gone a way. I eat, I shop online, I text, etc. Today my concern is simply…. So took a pill. In some cases caffeine appears to slightly enhance sedation brought on by zolpidem, the active ingredient in Ambien.
However, caffeine can also antagonize, or work against sedation. Each case is different. Still, you can improve chances for sleeping by avoiding caffeine, nicotine, beer, wine, and liquor in the four to six hours before bedtime. In the long term, you may want to seek out an alternative to Ambien, especially if it has stopped working consistently for you.
Yeah, I have been thinking its time to change. What kinds of alternatives for sleep should I talk to my doctor about. As you know from personal experience, we cannot MAKE ourselves fall asleep. Sleep is something that occurs as a result of allowing sleep to happen. Are you able to consider a lifestyle change in order to give yourself the best chance possible to get good rest?
Is is possible that stress is ruling your life? Does your diet contribute nutrients to your body or leave you depleted? Do you get minutes of exercise a day? Mother-in-law took one ambien, no problems, next night took one and would not stay in bed, disoriented etc. She had no deficits, took her own pills, did her own banking, cooked etc. Only change was the ambien. Is it possible she is still having side effects from the Ambien? These symptoms do seem really extreme. Yeah I talked about all that with my doctor before I even started sleep aids.
Unfortunately, none of the life changing styles helped. I take Prozac for anxiety…. Hi, I have been taking ambien for about 2. I travel a lot across time zones for work and have been dependent on it to get me to sleep as well when I am away from home. Can I taper off? How long should the tapering off last if so? Thanks so much, Michael. Yes, I did the whole thing: Until I fell down the stairs, came in and called an ambulance and my children. I was unconscious for three days.
I use unconscious becase it is the only thing I an think of. I immediatley went off ambien cold turkey. No, I did not sleep — I read books, watched TV — though terrible thoughts about what I would like to do to the doctor who kept prescribing this medication. It has been months now and through will power alone I have finally come to a place where I will sleep for a few hours — 4 to 6 usually. I am managing this.
I worked as a Paralegal; I hold a degree in Psychology and one in Philosophy. I feel like my brain will never work again -being awake is one thing — being able to think is another. I forget simple things — like where is the key? What did I do? And on and on. BUT, I am able to think more clearly every day. God willing, I will recover my brain. By the way I worked for and got my degrees in So, no I am not an addled old person!
Ambien is a strong sedative and requires medical supervision when you come off it. I urge you to speak with your prescribing doctor about stopping and withdrawal from Ambien. Additionally, cold turkey withdrawal from Ambien can precipitate more severe symptoms of abdominal and muscle cramps, vomiting, sweating, shakiness, and rarely, seizures. Although these symptoms are relatively uncommon, they are possible. And rebound insomnia can also occur. I applaud your effort to get off Ambien.
And also for your youthful openness and perspective about possible Ambien dependence and addiction. I wish you all the best! If I ran out of pills I was terrified of trying sleep without it. When I got pregnant I stopped it right away but started back on it once my baby was sleeping thru the night. It felt basically like a good buzz without having to drink. I enjoyed the effects and changes to my personality.
When on Ambien I was more brave, risk taking, attractive and aroused. It really is like an alternate personality. I love taking Ambien to be honest. I have done all the crazy things noted. Could it be connected to my meds? The Ambien and Lorazepam can both cause these problems. I had no idea! I had never made the connection. I thought it was just me. Since that day I have not taken any of those meds. Now I think all those fears of quitting were really just in my head.
I pray everyday that I do not have long-term or irriversable damage. I am so happy to have found this forum to know I am not alone, that others experienced the same feelings. I hope you all find the strenght to overcome this as well. Good luck to all……….. I had posted on here a month or so ago about the crazy effects that ambian was having on me sleep talking, texting, singing.. After taking Ambien I apparantly decided to go in the hottub.
I know I need to wean off, its been 10 years of taking them daily and I still have insomnia even with them so I am desperately afraid of no sleep and how horrible I feel when I even miss one night of them I am like a zombie. I applaud others efforts to wean off and so wish I had the courage to quit. I am definately thinking about locking myself in the bedroom after taking it so I dont end up in the hottub again. This medicine is serious business, to anyone consider taking it more than just occasionally, really think about it because it is very hard to sleep without it once you start your body needs it to sleep.
Thank you so much for sharing what your doctor told you about the long term effects of lorazepam, Mischelle. I had hysterectomy and had insomnia ever since. I am a pretty active, educated person. Feeling as if I am with it one minute and out of it the next during the day. My body aches etc. I thought I was getting sick and started telling my husband that I felt as if something seriously was medically wrong with me. It occured to me that Ambien may be to blame.
I found this site and appreciate everyone sharing their stories. I threw my pills down the toilet today and not taking any more chances. I can not believe this drug is even pushed by doctors. I have never felt so horrible in my life. My brain feels as if it is slowly leaving. I started to feel anxiety not realizing it was the Ambien, started taking anxiety pills during the day on top of the Motrin to combat my migraines. Never again, I would much rather go with out sleep. Never did deep sleep and cannot sleep w-cpap machine without some ambien.
I have had epsiodes of getting high. Excercise, eat well, but without it I get hrs a sleep a day. Tried everything natural before. It seemed like a miracle drug. Have been taking it now for almost 3 years. Definitely talking to my dr. I seem to be off balance alot and I thought it was just getting old, but this really makes me think if it is not the ambien. I never used to do that. Thanks for sharing more about your experience with Ambien.
Do you your cognitively impaired symptoms go away after taking ambien or is it permanently? Im having difficultly recalling the words I need to communicate my thoughts. How long have you been off Ambien? I had spina bifida occulta, which means a chronic irritated urge to urinate. I suffered a major trauma when 17 years old. After the hospitalization for the jejunitis, I was prescribed ambien, took on a nightly basis since I no longer sleep with my husband, my work has suffered tremendously.
I do not take the medicine if I know I will have a late night commitment. I have not increased my dosage in the entire six years I took this medication. I have stopped before for several months at a time with no luck, ending up in the shape I am fast approaching again. However, I am getting older and it is harder to bounce back from this. My biggest conscern has been the ongoing chest pain. If I seek a new dr. I can produce pharmacy and medical records to prove otherwise.
What am I to do? Yours is a rather difficult and complex case with lots of emotional undertones. I can understand as a new mother the real need for sleep and the frustration that occurs when you do not sleep well. I would personally look into major lifestyle changes in order to sleep better. First, create a log of ALL activities for at least a week. Then, ask for recommendations from trusted medical professionals: Everyone you can think of. Maybe there is something going on in your daily routine that you cannot see that is the key to getting good sleep.
No real problems as discussed in most of the previous comments. It really helps me fall asleep. I take it as prescribed, and just before going to bed. I am mostly concerned if there are any major health concerns from taking it for so long. Again, no complaints from it, just curious if I should quit taking it for long term health issues. There is currently no published data supporting the efficacy and safety of zolpidem beyond six months.
Long term effects could possibly intensify insomnia, rather than treat it. If you can sleep without Ambien, why not try something like melatonin for a while until you can even wean from that. Lifestyle changes such as regular minute exercise or daily meditation can significantly help sleeping problems. I am always so terrified of this cocktail of dangerous drugs. As with the other posters on this site, he pops all 5 of his assorted pills at bed time. He wanders the house and eats several times a night.
During the day, he normally eats nothing because he is up all night eating. He is also tired every day. He wakes up tired. For someone his age he should be so active but, he literally does nothing. At home he sleeps, complains about being sick, sore muscles, headache, stomach issues…. I think I get one day a month that he says he feels ok. It actually frightens me thinking about our up-coming wedding because I am a very active person and I feel that I am marrying a grandpa.
My 84 year old mom is more active. It seems most nights he cannot wait till it reaches 8 or 9 pm so he can take those stupid pills. As far as the Ambien wild intercourse part……that is not going on here. We get the minutes to hurry up and get the deed done before he starts snoring. I am reading the posts on this site tonight because I am so Fed Up. Got up 30 minutes later and ate a TINY bit of food which I prepared and within 10 minutes was back to bed sound asleep.
He got up about an hour ago to take his stupid pills and pee up for about 3 minutes ….. I am an active person. At his size and age, he should be able to do tons of stuff. I mow the lawn, do all the house work, take care of pets, climb ladders to change light bulbs …. I am seriously considering postponing or cancelling the wedding until he gets off this stuff.
As for talking to the doctors — good luck with that folks: I have twice now. I have argued with his doctor about this Ambien and the doctor tells me he needs it and that I am overly-worried over nothing. I have read several articles online about the VA and the Seriquel cocktails and it scares the hell out of me for him. The side effects of these drugs are terrifying. I just want my man to ba a man and not a zombie. I now plan to stop taking them as well in a week.
O, I was on Zanax for a two month span with the Ambien and took way to many of them as well and was falling over a lot but that has all stopped since I quit the Zanax. Best of luck to all, Fred. How long can you expect these withdrawal symptoms to occur? You can learn more here:. Hi, My neighbor has been taking Ambien for 7 years and is having problems with shortness of breath. What can I tell her about the long term side effects of Ambien?
Also, seek a consult with a pharmacist who cares. Thank you for sharing. I did not realize that people died from long term ambian use. What exactly is it that it does to kill people? Are they dying from physical side effects of long term use or behaviors associated with its use ambian driving…ect. This scares me silly. Though I take the same dose as I have for ten years my memory has suffered greatly. I am a graduate student and it is greatly affecting the quality of my work and everyday function.
When I mentioned to my doctor my memory problems I am 43 he called it something like early dementia suggesting perhaps it was associated with depression. My niece passed away in a drowning accident last summer and I admittedly have been quite depressed but the memory loss has been here much longer than that. I just feel like he was passing the buck on the memory loss when clearly I feel and from everything I have read the ambian is a huge contributer.
My son in law takes Ambian for ten years and in the last few years has added on Lunesta. Os it typical for a doctor to prescribe both sleep aids at the same time? He also takes two antidepressants. Hello, I have been taking Ambien for at least 3 years. Then I had to take a whole pill get to sleep. It seems like I get to sleep easily when I first go to bed, but I will wake up after 3 to 4 hours.
Am I permanently damaging my brain. I would like to stop taking Ambien,but I like to get a full nites sleep. What should I do? Just to be clear — it seems that you are Ambien-dependent and not Ambien-addicted. Dependence indicates the physical need for a medication or drug, while addiction indicates a psychological or emotional need. And once you get Ambien out of your system and go through withdrawal, you can learn to sleep again naturally.
And simultaneously, you might seek out a sleep professional or sleep center that can teach you how to sleep again. Rubin Naiman has some great books and teachings about sleep. Or there may be a sleep center near you. Lifestyle adaptations and changes can work wonders for difficult sleeping patterns. I am menopausal and insomnia has ruined my life prior to ambien. I only take 5mg at night and sleep like a baby and am energized all day long. I have none of the bizarre side effects that are listed.
Why should I stop taking this and return to insomnia hell? Melatonin and Benadryl have not worked for me in the past. Thank you for any insight! I have blogged on here in the past to reach out for support and information, for that I thank this Blog! I decided that after years of using Ambien, it was time to stop. I broke it down like this, I do not want to have to take a pill to do one of the most natural things in life… sleep.
Sleep is important and when disrupted for a long time can be unhealthy, but what about putting this pill in my system every night?? I am not prescribing this but simply sharing this. I decided to stop taking Ambien, so I just stopped. Sure, I had about a week of on and off restful sleep, mostly off… but I am now off of it for about 6 weeks and am averaging about hours of sleep each night… ON MY OWN.
So, it can be done. I have actually had a really good experience with long-term use of Ambien, because I had terrible insomnia for many years, and when I started taking Ambien I could sleep, and then all my worrying about not being able to sleep was let go. So just knowing that Ambien is out there has greatly reduced my anxiety. I just worry about any other physical effects from the meds. I am physically dependent on ambien, but have tried all of the alternatives OTC, herbal, other z-drugs, benzos, trazodone, mirtazapine, off-label SSRIs and nothing else helped.
I have been taking ambien cr for three years. I feel sluggish,have tachycardia and am just tired of having no energy. I have been cleared through my cardiologist—no heart problems??? I would like to get off the ambien but I am so addicted to ir now that I feel stuck. I need to sleep. I was prescribed zolpidem ambien over two years ago.
I was forced to stop taking the drug without weaning- just a cold turkey stop. I have been going through withdraw now for two months, with dizziness, headaches, nausea, irregular heartbeat and other problems that I am not sure may have to do with the use of the drug, or the discontinued use of the drug. At the least, mild dysphoria and insomnia, abdominal and muscle cramps, vomiting, sweating, tremors, convulsions, fatigue, flushing, lightheadedness, nervousness, and panic attacks may occur.
I feel like I am addicted to Ambien. I have take 5 to 10mg every day for the last 2 years. I am 36 years old and had struggled with insomia for years before finally finding some relief with Ambien. For the most part it has worked for me and have not experienced any of the serious side effects like sleep walking. I have never taken more than 10mg. My intention was to never to be taking the pill this long.
Or, at least I would like to limit it to just taking during the two weeks prior to my period, which is when I find it most difficult to sleep. But, as soon I make the decision not to take a pill, my body begins to react. I begin to panic. My heart feels like it is racing. I feel uncomfortable an anxious. Soon the fear of not getting enough sleep for work the next day always leads me to give in and take a pill.
I have been taking Ambien for about 14 years and I know I am addicted to it. But the thought of not taking it just causes major anxiety issues. I am already on Celexa and Klonipin, for the depression and anxiety. I have been reading about all the side effects that ambien is causing. But some sleep is better then none. I also do have a glass of wine or a beer after I take the ambien. Is Lunesta any better for you???? I took ambien for over 4 years and I recently quit cold turkey…well I supplemented with melatonin and valerian root.
During use and even now, I wake up with uncontrollable shaking hands and tremors. My hands are shaky throughout the day, making it hard to write, eat, drink or keep my hand on the mouse while on the computer. I will accidentally click on things because of the shaking. I am an ambien user of two years. I take one 10mg pill every night. This blog is only one side of the story.
I am telling mine. I am not discounting any of the users here who reported bad experiences. I am merely providing an alternative experience that was not. By the way, I do not like the advice being doled out here for meditation as a safe alternative to medication or other relaxation practices. While we should be cautious of our prescribed medications, I warn that meditation has been associated with spaciness, disconnect from reality, detachment to the point that normal, human responsibilities and relationships seem unimportant.
Not all meditations are alike. Not all meditative practices will work for everyone. I am not sure if I am allowed to post sources here at this blog, but medical studies do exist that show adverse reactions to meditation. Solomon Snyder, head of neuroscience at Johns Hopkins University, warns that during meditation the brain releases serotonin.
This may help those with mild depression but too much serotonin can cause, in some, a paradoxical relaxation-induced anxiety. Instead of relaxing during meditation, these people become distressed and may even have panic attacks. Snyder says that in some cases of schizophrenia, meditation can launch a person straight into psychosis. I have been on ambien steadily for about a month now. I work 24 hour shifts and do not take ambien on those nights. I work in a stressful job and my sleep patterns are erratic due to the nature of the business.
I was hoping that a week of being on it would reset my sleep pattern. I have even cut down caffeine and sugary foods after 4pm to help me get to sleep. However at the end of a 24hr shift if I am exhausted I sleep for hours unassisted. Last year, there were sixty million prescriptions for sleeping pills in the U. Pelus-Kaplan, a retired professor of early-modern history, teasingly explained that her husband almost never takes medication.
Zolpidem is part of a third generation of synthetic compounds that treat insomnia by attaching to GABA receptors. Such drugs were first introduced a century ago, long before the gaba system was identified. In the second, safer generation are benzodiazepines, a class that has some mixture of sedative, muscle-relaxant, anticonvulsant, anti-anxiety, and amnesiac effects. He synthesized Librium and then Valium, which, between and , was the most frequently prescribed drug in the Western world. Valium was marketed as a treatment for anxiety, but insomniacs also used it.
The first benzodiazepine explicitly approved by the F. Kaplan, who had grown up in Paris, was then a few years out of college. A mountain climber, he was long-haired and instinctively unaccommodating. I did not fear anybody. He is not Jewish. After he identified some compounds with anticonvulsive properties, he felt that one of them was being improperly accelerated toward commercial development.
Kaplan says that this disagreement, along with his activities in a trade union, had already begun souring his relations with the company when, in , a colleague made a passing suggestion: Zopiclone, a compound that had been created several years earlier by a rival company, was an interesting oddity. Although its chemical structure was quite unlike that of a benzodiazepine, it acted just like one.
It eventually beat zolpidem to market, as the first in a new category of sleep medication: Lunesta, approved by the F. That was the gist of the invention. The molecule, when finished, had another important characteristic. At the lunch table, Kaplan began sketching in my notebook the chemical structure of LSD. He drew hexagons attached to other hexagons. One of them had a tail of nitrogen, oxygen, and carbon. This tail helps to make LSD unusually effective at reaching the brain from the bloodstream.
Maybe it increases the activity one hundred or one thousand times. Colored one-inch spheres, representing atoms, were connected by thin rods, creating models the size of a shoebox. This was a more empirical, architectural approach than is typical in a lot of pharmaceutical chemistry. Kaplan and George tried to identify what these molecules had in common, structurally, that allowed them to affect the brain in the same way. George wrote a report describing a few possible types of new chemical compounds.
Working separately, they built molecules of the first two types: A third series, made by George, looked better. After the very first compound, I knew. Kaplan heard only rumors about how the compounds were testing. The company knew that one of the compounds had far more pharmaceutical promise than the others, but did not need to disclose this to industry competitors. So the star molecule was also hidden from Kaplan, even though his name was at the top of the document.
He showed me the patent. He looked down a list of seventy-seven chemical formulas, and pointed to the seventy-fifth: The company eventually moved him to an office in central Paris, to a phantom job in an empty room. And then he decided to study law. I would say paranoiac. Since he was paranoiac, he was very happy to be frustrated—it was a part of his happiness.
After the patent filing, it took some years before zolpidem reached the market. He said that drug development accelerated in , when a company pharmacist, preparing a batch of syrup for the first human trial, accidentally swallowed a teaspoonful of the drug. He immediately fell asleep. Zolpidem had more impact on sleep than on amnesia, muscle relaxation, and the other effects associated with drugs that bind to gaba receptors. In theory, at least, this selectivity meant that the drug would have fewer undesirable outcomes.
Zolpidem was launched in France in Pelus-Kaplan once attended a conference, incognito, to confirm that her husband was being overlooked. It was George who built the molecule, but Kaplan argues that the initial collaboration created the blueprint for all that followed. Ambien had the good fortune to reach the market just as the reputation of Halcion, which had been promoted as safer than barbiturates, collapsed.
It remains available in the U. And a fatal overdose would be very hard, if not impossible, to engineer. Nevertheless, Ambien was accepted as a better drug. Then I show them the data. Ambien quickly became the national best-seller in its category. By the turn of the century, there were more U. In , Kaplan negotiated a payment—about thirty thousand dollars—from his former employers. George, who stayed at the company, happily, until his retirement, in , received a little less.
After Kaplan retired from his career in law, he formed an organization that lobbies on behalf of people who invent things while working as a salaried employee. Therefore, I call it a comfort drug. Ambien can be disinhibiting and depersonalizing. When the neurotransmitter sticks to its target, negatively charged chloride ions flow into cells, making the inside of the cells more negative, and less likely to fire. Many people experience this as a contented swoon that silences inner chatter while giving a half glimpse of childhood; they are overtaken by sleep, like a three-year-old in a car seat.
But others resist sleep and embrace the woozy, out-of-body license. After taking the drug, they larked around and knocked on the doors of other athletes. But for many Ambien users, like the eBay shopper, their activities on the border of wakefulness and sleep are less purposeful. He had Ambien and an anti-nausea medication in his body.
By the following spring, the F. This kind of behavior can occur during dreamless, slow-wave sleep—the state of an unmedicated sleepwalker—or, more commonly, Jed Black suspects, while someone is awake but disinhibited, by Ambien alone or by Ambien and alcohol. Black noted that this altered state can be mischaracterized as sleep by people who have forgotten their adventures.
A recent study, described in European Neuropsychopharmacology, suggests that these phenomena affect five per cent of users. Other studies have reported lower numbers. Thomas Roth, the director of the sleep center at Henry Ford Hospital, in Detroit, who has consulted for Merck and other pharmaceutical companies, told me he has not yet seen persuasive evidence that there is more of this behavior among Ambien users than among the rest of the population which includes drinkers. There may be other risks associated with zolpidem.
In a recent paper in the online edition of the British Medical Journal , Daniel Kripke, a professor emeritus at the University of California San Diego School of Medicine, examined five years of electronic medical records collected by a health system in Pennsylvania. He compared more than ten thousand patients who had been prescribed a sleep medicine—most commonly Ambien—and more than twenty thousand patients who had not. After adjusting for age, gender, smoking habits, obesity, ethnicity, alcohol use, and a history of cancer, and after controlling, as much as possible, for other diseases and disorders, Kripke found that people who had taken sleeping pills were more than three times as likely to have died during the study period as those who had not.
Those on higher doses of the drugs were more than five times as likely to have died. That is, more than four hundred thousand Americans a year. Kripke acknowledges that his study did not identify the cause of any death; ill people take more sleeping pills than others, and some users might have had illnesses that were undiagnosed, and therefore not controlled for in the study.
And insomnia itself could present a significant health risk, although Kripke resists that idea. Jed Black finds the data interesting but too inconclusive. Other research has linked zolpidem and similar drugs to depression, suicide, and car accidents; there are also data connecting zolpidem to cancer. Such numbers do not establish causation. If the public has largely overlooked such data, even as it pays attention to Patrick Kennedy—or to his cousin Kerry Kennedy, who was arrested last year with zolpidem in her body, having driven for several miles on a shredded tire after colliding with a tractor-trailer—it may be because Ambien deaths are disguised by circumstances.
John Renger, the Merck neuroscientist, has a homemade, mocked-up advertisement for suvorexant pinned to the wall outside his ground-floor office, on a Merck campus in West Point, Pennsylvania. A woman in a darkened room looks unhappily at an alarm clock. At Merck, these are handed out when chemicals in drug development hit various points on the path to market: Renger showed me one. Two years later, MK became suvorexant. If suvorexant reaches pharmacies, it will have been renamed again—perhaps with three soothing syllables Valium, Halcion, Ambien.
How many get to develop a drug that goes all the way? Probably fewer than ten per cent. In , when Renger was in Japan, finishing his postdoctoral work, two groups of scientists announced almost simultaneously that they had identified, in rodents, a previously unknown neurotransmitter. One group, in San Diego, called it hypocretin, after the hypothalamus, the area of the brain where it is produced.
Orexin-abundant mice gained more weight than others on the same diet. The orexin papers were widely noticed, in part because of the connection to feeding. Several pharmaceutical companies, including Merck, began investigating possible obesity treatments. A year later, a remarkable paper from Stanford sent everyone in another direction. Since the seventies, Stanford sleep scientists, led first by William Dement, had bred narcoleptic dogs.
This was an achievement in itself. The animals suffered from extreme daytime sleepiness and had a propensity for mid-coital collapse: The first Stanford dog was a poodle named Monique. Later, there were other breeds; the Stanford colony, mostly Dobermans, had eighty dogs at its peak. Narcoleptic dogs gave birth to narcoleptic puppies; the disorder in canines has a single genetic cause. In , after a decade-long search, a team led by Emmanuel Mignot, a researcher at Stanford, located the damaged gene, and reported that it encoded a receptor: Narcoleptic dogs lacked orexin receptors.
Mignot recently recalled a videoconference that he had with Merck scientists in , a day or two before he published a paper on narcoleptic dogs. He has never worked for Merck, but at that point he was contemplating a commercial partnership. In narcoleptic humans, the cells that produce orexin have been destroyed, probably because of an autoimmune response.
Orexin seemed to be essential for fending off sleep, and this changed how one might think of sleep. We know why we eat, drink, and breathe—to keep the internal state of the body adjusted. But sleep is a scientific puzzle. Orexin seemed to turn notions of sleep and arousal upside down. Mignot had done something very unusual: An orexin receptor is the kind of place that many existing drugs are designed to reach.
A drug that activated orexin receptors might help treat narcoleptics, and a drug that blocked orexin receptors, if introduced to a brain producing orexin at unwelcome times, might help insomniacs, perhaps without intoxicating them. Pharmaceutical companies were reluctant to give up their obesity-drug ambitions, but it seemed that the orexin mice described in were fat because they stayed up late and had more time to eat. Insomnia was not one of them. Should Merck invest in a market dominated by a drug that, within a few years, would become a cheap generic?
Indeed, one detects a little professional defensiveness from the suvorexant team. Renger can sound effortful when describing the distress of insomniacs: But orexin-related work promised pharmaceutical novelty, which is extraordinarily uncommon. Most new drugs are remixes of old drugs—clever circumventions of patent protections. The last truly original medicines in neuroscience were triptans, for the treatment of migraines, introduced in the early nineteen-nineties.
The work was also feasible. Renger, upon his arrival at Merck, had set up a sleep laboratory that could make very fast, semiautomated measurements of the sleep patterns of rodents and monkeys. The lab was designed to identify sleep-related side effects of Merck compounds, but was well suited for testing insomnia treatments. Merck has a library of three million compounds—a collection of plausible chemical starting points, many of them the by-products of past drug developments.
I saw a copy of this library, kept in a room with a heavy door. Rectangular plastic plates, five inches long and three inches wide, were indented with hundreds of miniature test tubes, or wells, in a grid. Each well contained a splash of chemical, and each plate had fifteen hundred and thirty-six wells. There were twenty-four hundred plates; stacked on shelves, they occupied no more space than a filing cabinet.
In , Merck conducted a computerized, robotized examination of almost every compound in the library. Plate by plate, each of the three million chemicals in the library was introduced into this soup, along with an agent that would cause the mixture to glow a little if orexin receptors were activated. Finally, orexin was added, and a camera recorded the result.
Renger and his colleagues, hoping to find a chemical that sabotaged the orexin system, were looking for the absence of a glow. I visited the room in which this work had been done. Yellow robotic arms, on the same scale as car-assembly robots, were moving the trays from here to there, making bursts of sound like a nut being loosened in a tire shop. A computer monitor showed enhanced images of reactions on the plates: The molecules that best blocked orexin receptors were re-screened, in various ways.
Renger took me to see the rats and monkeys. The lab has soundproofed walls built out of the kind of air-infused blocks used in bomb shelters. The rats were transmitting live EEG data, wirelessly, from brain implants. So were the monkeys; they also had touch-responsive screens in their cages, on which they sometimes played games, for rewards of juice. A red square might appear on the screen and then disappear; after a pause, a red square might appear alongside a yellow square, and the monkey would be rewarded for touching the red one.
With these games, Renger could simultaneously measure wakefulness and cognition. The work went back and forth between the chemists and the biologists: At the monthly meeting of the pre-clinical-development review committee, they pitched their best bet to the company. But Renger wanted the drug to extend sleep. Merck approved the compound. The company was now likely to fund at least a year or two of work.