A highlight from How Buspirone Mixed with Melatonin to Make an Antidepressant
This traits anxiety without any bins are like ever effects. It is a serotonin five. Ht one a agonised which is the same mechanism that fuels the angsi olympic properties of selection the german extractive lavender that we reviewed for ged last august the anti-depressants fillets earn vibrated and forty oxen. Trim telex also shared this mechanism as dominion atypical. Antipsychotic which partial agonists a five. Ht one a such a rip hip result. A centipede clause a pain. Lorenza darn quote hyping and zip president bo all of those touch on five. Ht one a the effect sizes are not the same. If you've been reading every issue of the carlisle report. I'm sure you have those effect sizes in your head but here's a rundown anyway vortex teen in. Ged the effect sizes around point one so small that we don't really think it works boost sperone the effect size around point point three still kind of in the small range but enough to get fda approval. The successor is an s nri's which don't touch five ht. One eight are around point. Three two point four the benzodiazepines bring us two point. Five point six and then there's silex and lavender with an effect size of point eighty seven now when it comes to depression boost sperone popular augmentation strategy for antidepressants but the research. Supporting that use is not as strong as its popularity would suggest but there are still some good reasons to use postpone in depression. We get into some of them in the online edition and one we're going to cover here is when it's paired with melatonin. This is a very interesting story of drug development to medications that don't treat depression on their own. Boosts brown and melatonin just might treat it when combined together. It all started ten years ago in marisha fathers group at massachusetts general hospital were screening drugs for their potential depression. They did this by testing them. In so cultures of primitive undifferentiated human brain cells to see if the medications cause cell growth or neurogenesis. The background on this is that one cause of depression is shrinkage of brain cells in the hippocampus most antidepressants increase. Segler growth there. As does ec t and aerobic exercise and blocking this neurogenesis renders antidepressants ineffective who sperone induce neurogenesis in this platform. But there was a problem when they added it to the dish of undifferentiated brain cells. It caused those cells to develop into brain cells but it also triggered them to develop into non neuronal cells like astra sites. This is not what they wanted. They wanted the neuro growth. Thanks to be concentrated in the brain cells especially in the hippocampus so they looked for something that can add the boost brown to inhibit. Those other affects one of their collaborators. Andrew nurnberg had published case report in two thousand nine where he was able to treat treatment resistant. Bi-polar depression with a combination of melatonin and low dose boost perron along with seventy five milligrams of the appropriate and some lamotrigine. This led to some thinking that boosts prone melatonin might have unique antidepressant effect so they ran the combination through the cell line and it worked the new combination cause neuronal growth but not other kinds of cell growth next. They tested it in animals to make sure it had antidepressant effects at a behavioral level. And to get the dose. Just right right did they use low doses corrode they were aiming for a lower doses possible to improve tolerability earlier. Studies had suggested that boost. Sperone might have antidepressant effects at high doses like above forty milligrams a day but most patients weren't able to tolerate those doses so in a way they were hoping to get those antidepressant effects at a lower dose through this melatonin synergy said they went from the petri dish in vitro to animals. In vivo. a. What about in humans that came next and by the way they reported all four of these experiments in one single paper so next day recruited one hundred and thirty four people with moderate major depression volunteered at take the drug for a six week randomized controlled trial everyone either got placebo boo sperone fifteen milligrams a day or the boost brown melatonin combination which was fifteen milligrams of bruce brown and three milligrams of melatonin sustained. Release the melatonin. They used was for mellon medical products. And if you google that it's spelled m. e. l. l. e. n. you'll see it's available on their website very foldable. Just six dollars a month. So dr aitken. What was the result. The boost brin melatonin combo had a significant effect on the primary outcome the clinical global improvement scale as well as on secondary outcomes. Like the overall. Cgi severity level the hamilton anxiety scale and remission rates on the quids depression inventory. But not actually on the total quits score depression score itself which is okay. We don't expect treatments to succeed on every secondary outcome. the combo did better than placebo. That did it do better than boost parental on yes. it did better than both boost. Brown alone and placebo. On all of those measures boost broendby by itself did not work on any of those measures. Actually not even anxiety. But i guess that's not too surprising when you consider the dose was only fifteen milligrams a day okay. But he's my theory. What at this just proves that helping sleep of melatonin and helping anxiety with a little boost. Perron treats depression. I mean there are studies where zappa clone esta is added to as sarai and. It makes the work better. I've seen that a controlled trials of depression as well as generalized anxiety disorder. And if you've not seen those studies and you're thinking like what Clone is an antidepressant. Go to our website and click on podcast at the car. Report dot com. We have all the key. References linked now kelly while that is a good theory in this case. The melatonin actually didn't improve any sleep items on the rating scale. So the thinking is that it's antidepressant. Effects were due to some kind of pharmacodynamics synergy with boost brown perhaps neurogenesis rather than a direct effect on sleep on the other hand. They did look at cognitive symptoms in a separate study and from that analysis. It looks like the improvements in cognition rather than sleep were. What was the driving change and depression when they compared patients who responded to the combo treatment versus those who did not it was the change in cognitive symptoms. That seem to make the difference. That makes sense.