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Great Combo for TRD. Prozac + Zyprexa + Adrafinil

Posted by JohnL on August 19, 2001, at 6:24:16

For anyone having trouble with TRD, treatment resistant depression, a great combination to try is Prozac + Zyprexa + Adrafinil. Why exactly this combo works so well can be partially explained, but much of it is a mystery. Dosages that work for me are 20mg Prozac with breakfast, 300mg Adrafinil with breakfast, 5mg Zyprexa with dinner.

I see so many people here suffering and struggling with things like plain jane SSRIs, Buspar, Pindolol, MAOIs, and mood stabilizers of all kinds. I wonder why they and their doctors just don't go straight to the meds with the strongest time-tested track records, such as the three in this combo.

My observations and opinions on these three drugs are based on both anecdotal observations as well as clinical evidence and scientific studies. The scientific studies alone are so numerous it would be impossible to print them all here. Just keep in mind that whatever I say in this post, there is indeed ample scientific evidence to support it.

I have often wondered why this combination works so well. I have come up with some partial explanations, but they are admittedly purely layman style and not complete.

Prozac, in my opinion, is still the gold standard SSRI. My local doc has 200 patients on it, but only 50 patients on all other SSRIs combined. In a way, this is indirect evidence that in a real world office setting, my doc has greater success with Prozac than anything else. Prozac is not purely serotonin selective. It also has some affinity for norepinephrine, and it also has indirect effects on dopamine. It is less likely to cause numbing of emotions, and less likely to cause sexual dysfunction. But when it does, that's where the other meds in the combo come into play. They counteract any unwanted side effects. For many people with TRD, some physical and mental stimulation would be viewed as a good thing. Prozac is generally known for doing exactly that. The other SSRIs are more associated with sleepiness, sluggishness, and numbness.

Zyprexa at low doses feels like it stimulates dopamine, as well as serotonin and norepinephrine. It counteracts Prozac's insomnia, it counteracts any sexual dysfunction, and counteracts any anorexia. And it provides a good quality sleep, which is usually a welcome relief to someone suffering from TRD. According to clinical studies, there is some special synergy between Prozac and Zyprexa. Together they dramatically boost serotonin, NE, and dopamine, much more so that when Zyprexa is combined with any other antidepressant tested. The dramatic increase in neurochemicals from the combination is postulated by scientists as being one reason why the combination has a profound effect in treating TRD.

The final link in the chain is Adrafinil. It is known as a 'good arousal' drug, which provides stimulation, interest, motivation, creativity, memory enhancement, without the unwanted side effects common to stimulants. Though it is classified as a psychostimulant, in Europe it is more often viewed as an antidepressant. It does not generally come with the insomnia or anxiety of other stimulants. Its primary mechanism is as an alpha-1 agonist, though as with all meds the exact mechanism is unknown and debateable. From the way it feels, I would say it mimics norepinephrine. The end result is that you can enjoy all the benefits of increased NE function without the horrible side effects of increasing real NE amounts. If there is any malfunction in your NE chemistry, Adrafinil fixes it without increasing neurotransmitter levels. Many of the side effects are desireable, such as increased interest, motivations, memory, and creativity. If the SSRI in the combo causes any emotional numbness, Adrafinil fixes that. It also has been shown to have indirect effects on boosting dopamine D2 receptors.

With these three drugs, practically all the bases are covered. Whatever the cause of your symptoms, this combo is very likely to target the real underlying problem. And for those who think they need a mood stabilizer, Zyprexa is FDA approved for bipolar. No need to waste time on the mood stabilizers, which seem to disappoint more often than not, at least at this board anyway.

I admit I probably sound like a broken record in my posts, because I continually repeat my praise for these three drugs. But there is a reason for that. They work. It's that simple. I wish the explanation of why they work was simple, but regardless, the fact that it works is really all that matters. As a rough observation just at this board, 80% of people who have tried any two of the three drugs in combo have been very pleased with the results. To date I think I am the only one on all three. But I would humbly and confidently propose that 90% of people at this board who are having trouble would experience dramatic improvement with this combo. It covers all the chemistries, it works in different parts of the brain, and it results in near total recovery with a near absence of side effects. Why in the world someone would waste time on other things is a mystery and a frustration to me. Of course, I've been there and done that too. That's why it is frustrating to watch.

Forget all the other stuff. Narrow the universe down. Go straight to Prozac + Zyprexa + Adrafinil. You should know within two weeks, and often within 24 hours, if this combo will be promising for you. Then if it fails, go back to all the other stuff. If you have ever tried Prozac or Zyprexa or Adrafinil one at a time and were not happy with them, do not let that stand in your way. That's because they combination works totally different than any one of them alone.

Believe me, I understand mileage varies. That's why I tend to suggest something with the highest mileage potential. I have seen and observed much greater success with any combination of these three drugs than I have with MAOIs, mood stabilizers, or anything else. At this board as well as in my doc's office. It's purely anecdotal observation and purely subjective, backed up by clinical scientific evidence. For everyone having a difficult time, I honestly feel it is a waste of time, and begging for torture, to consider anything else until these three drugs have been tried first.

Many people will scoff at this post. That's ok. Those who do will probably continue to struggle and suffer. Those who take the leap of faith and actually try this combo will likely be glad they did. I just wish I was a salesman for these drugs so I could reap the commissions! :-)
John


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poster:JohnL thread:75566
URL: http://www.dr-bob.org/babble/20010814/msgs/75566.html