A highlight from Can A Sleep Med Augment Antidepressants?


The dark ceiling. That's the last stanza of poem by rubbed penn. Warren and tells us something about what. It's like to be depressed and unable to sleep when the lights down the ceiling. Stark there is nothing to distract from the rim initiative thoughts that make depression so painful. Last month we covered the long complicated relationship of benzodiazepines in depression. The culminated in over a dozen controlled trials with the benz owes in particular alparslan. Xanax did a pretty good job of relieving depression. Even compared head to head against a tricyclic antidepressant. Today we're going to talk about the successor to the bentos the z. Hypnotic and whether they can augment antidepressants in depression and anxiety disorders. They uphold the z. Hypnotic because all of them start with the letter z. I came sopa clone. I'm a vein which is not available in the us but has been used in europe since nineteen eighty six then zoll pit him ambient released in nineteen ninety-two after that zell applaud sonata released in nineteen ninety nine and then there's is up a clone nesta released in two thousand and four in the us. It's that last. One will be focusing on today because it has the most studies in depression and anxiety s zorba clone is not widely available outside the us but for our international audience. It's pretty similar to the originals. E hypnotic zappa clone zappa clone is composed of two mirror image stereo isomers the l. n. s. zappa clone summers. And they're together in a fifty fifty mixture so that means the typical dose of zappa tone. Seven point five. Milligrams contains three point. Twenty five or fifty percent milligrams of s zaba clone which is just about the same. As the maximum dose. We use in the us of three milligrams. So if you've ever prescribed zappa clone you've also given s zappa clone. We know of only one clinical study that compared these to clone hypnotic six it was a randomized trial that compared the two dosages of the drugs the typical dosages seven point five and three milligrams in one hundred ninety nine patients and it found that they were virtually identical in both their clinical and adverse effects which included polycom niagara fy data however. There are also a few non-political studies in healthy volunteers of these two drugs. And those found that s clone works. Faster comes on faster and it doesn't linger as long. It comes off faster as well compared to zap it loan which would suggest that the si summer is a little more favourable in its pharmacokinetics. You know you really have to wonder. Why would anyone fund a head to head of two similar drugs that both generic not even available in the same country. This study was funded by your afam. Her recently launched a zappa clone in brazil. Brazil is the only country we know of here where both is a coin and zappa clone are valuable. The euro farmer wanted to reassure brazilian physicians that the new version was at least non inferior. Now that we've clarified that these two drugs are pretty similar. Let's look at the zappa. Clones might differ from others e hypnotic although they all start with the letter z or s z in the case of sa flown these medications have different chemical structures. They're different enough. That each actually has its own. Structural class zoltin. Ambien is an image. As appearing zahle upon sonata is a pyro solo pyramid dean and the zappa clones are classified as cyclo appear loans. But what do they do. In the brain. All of these drugs act on gabba a receptors. Which is the same. Receptor that the benzodiazepines act on. But the ben's are used for sleep and anxiety while z. Hypnotic are only used for sleep. You often hear that. The reason for this difference lies in a simple pharmacodynamics fact the z. Hypnotic only affect the part of the gabba a receptor. That's involved in sleep. The alpha one sub unit while the benzoate affect alpha two three and five subunits which are involved anxiety. But that's not quite the whole story. There's onesie hypnotic that is not selective alpha one and it spreads its activity out among the angsty olympic alpha two three and five sub units. And that one you guessed. It is clone as well as its american cousin. S zappa clone. Which means we might expect. The zappa claims to have more angry. Olympic effects than the other z hypnotic. At least in theory. Let's look what happens when we tested out. In people and animals when's cloned was first discovered. They tested at mice to see if it affected them like the benzodiazepines do and indeed. It did my son's clone melissa aggressive and anxious much as they are on benzodiazepines. Most animals studies concluded that zappa cloned has a very similar behavioral profile to the bentos. The human studies came next in one thousand nine hundred eighty nine and nineteen ninety. Two small controlled trials came out comparing zappa clone to some of the benzodiazepines that are often used for sleep. Those are try as the lamb and the european nitrates pam in both studies the z. Hypnotic and benzodiazepine had similar effects on sleep but the patients who took z. Hypnotic consistently had less anxiety. Now that's a surprising finding considering that it was compared to a benzodiazepine but the same thing happened again. When a japanese scoop of researchers compared zappa clone to the benzodiazepine mid data lamb for anxiety before surgery only clone reduced the pre operative anxiety. The benzodiazepine did not so far. We have a few small studies with some early indicators. Zaba coined may reduce anxiety. Much like the benzodiazepines do but the bigger studies came later with his oppa clone and they were sponsored by its manufacturer. Sip precor in two thousand six mauricio foreign colleagues wanted to see if patients with depression got better. When their sleep was treated intuitively. It makes sense. Insomnia is a risk factor for depression and depression is associated with all sorts of sleep complaints and yet the idea had never been shown to work before so this study i'm gonna mention is a first of its kind. They recruited over five hundred patients with depression and take part and everyone was started on the antidepressant fluoxetine prozac half of the patients were also started on s software cohn at the same time and the other half were given placebo at night at the end of this eight weeks study. Those who got the zappa clone were less depressed than the patients on placebo and this difference even held up when they removed the sleep. Items from the depression rating. Scale the sleep medicine as oppa clone. Lou nesta also brought about a faster antidepressant response. So was it something about sopa clan or was it just that anything that improves sleep will improve depression after all we've since learned that behavior therapy for insomnia cbt. I treats depression and augments antidepressants and keep in mind. The patients in that study had insomnia and depression. So we don't know if so picone treats depression and people who

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