[erinkj]

Blood test may help in choosing antidepressants

A blood test may help make the antidepressant decision somewhat easier. The test, called the cytochrome P450, helps pinpoint genetic factors that influence your response to certain antidepressants (as well as some other medications). The test doesn't predict which antidepressant will work best for you. But it does help suggest which ones may not work, and which ones may have the greatest side effects specifically for you.

What is the stress response?

Stress response, often referred to as the "fight-or-flight" reaction, is your body's rapid and automatic switch into "high gear." It's easy to imagine how this reaction helps you deal with a physical threat. You need the energy, speed, concentration and agility either to protect yourself or to run as fast as possible.
When you encounter such a threat, the hypothalamus, a tiny region at the base of your brain, sets off an alarm system in your body. Through a combination of nerve and hormonal signals, this system prompts your adrenal glands, situated atop your kidneys, to release a surge of hormones — the most abundant being adrenaline and cortisol.
Adrenaline increases your heart rate, elevates your blood pressure and boosts energy supplies. Cortisol, the primary stress hormone, increases sugars (glucose) in the bloodstream, enhances the brain's use of glucose and increases the availability of substances that repair tissues.
Cortisol also curbs functions that would be nonessential or detrimental in a fight-or-flight situation. It alters immune system responses and suppresses the digestive system, the reproductive system and growth processes.
The complex alarm system also communicates with regions of the brain that control mood, motivation and fear.

Stress response working overtime

The stress-response system is self-regulating. It decreases hormone levels and enables your body to return to normal once a crisis has passed. As levels of the hormones in your bloodstream decline, your heart rate and blood pressure return to normal, and other systems resume their regular activities.
But physical threats aren't the only events that trigger the stress response. Psychological "threats" — such as the stress associated with work, interpersonal relationships, major life changes, illness or the death of a loved one — can set off the same alarm system. The less control you have over these potentially stress-inducing events and the more uncertainty they create, the more likely you are to feel stressed. Even the typical day-to-day demands of living can contribute to your body's stress response.
Also, many of our modern stressful circumstances, unlike most physical threats, tend to be prolonged. Consequently, you may be running on the fight-or-flight reaction longer than it's intended to operate. What's good for your body in a short-term crisis can be very harmful over long periods.
The long-term activation of the stress-response system — and the subsequent overexposure to cortisol and other stress hormones — can disrupt almost all your body's processes, increasing your risk of obesity, insomnia, digestive problems, heart disease, depression, memory impairment, physical illnesses and other complications.

Digestive system

It's common to have a stomachache or diarrhea when you're stressed. This happens because stress hormones slow the release of stomach acid and the emptying of the stomach. The same hormones also stimulate the colon, which speeds the passage of its contents. Chronic hormone-induced changes can increase your appetite and put you at risk of weight gain.

Immune system

Your immune system is a complex balancing act between components that operate as an all-purpose emergency crew and more specialized components that deal with specific disease agents. The immune system, like the hormone system, evolved so that it could quickly deal with physical threats. Indeed, cortisol is one factor that prompts the system to reprioritize its tasks.
These shifting priorities are essential for priming the immune system to respond quickly to injuries, like creating inflammation around a bite or puncture wound, but these changes are not beneficial in the long run. When you experience chronic stress, some features of your immune system may remain suppressed, making you susceptible to infections. Other features of the immune system may be permitted to run unchecked, increasing your risk of autoimmune diseases, in which your immune system attacks your body's own healthy cells.
Stress may also worsen the symptoms of an autoimmune disease. For example, stress can trigger lupus flare-ups.

Nervous system

Certain byproducts of cortisol act as sedatives, which can contribute to an overall feeling of depression. If your fight-or-flight response never shuts off, the stress hormones may contribute to persistent and severe depression, as well as feelings of anxiety, helplessness and impending doom.
Such stress-induced depression often results in sleep disturbances, loss of sex drive and loss of appetite. It also may make you more vulnerable to developing certain personality or behavioral disorders.
Studies also suggest that chronic activation of stress hormones may alter the operation and structure of brain cells that are critical for memory formation and function.

Cardiovascular system

Chronic activation of stress hormones can raise your heart rate and increase your blood pressure and blood lipid (cholesterol and triglyceride) levels. These are risk factors for both heart disease and stroke.
Cortisol levels also appear to play a role in the accumulation of abdominal fat, which gives some people an "apple" shape. People with apple body shapes have a higher risk of heart disease and diabetes than do people with "pear" body shapes, in which weight is more concentrated in the hips.

Other systems

Stress worsens many skin conditions — such as psoriasis, eczema, hives and acne — and can trigger asthma attacks.

Individual reactions to stress

Your reaction to a potentially stressful event is different from anyone else's. Some people are naturally laid-back about almost everything, while others react strongly at the slightest hint of stress — but most fall somewhere between those extremes.
Genetic variations may partly explain the differences. The genes that control the stress response keep most people on a fairly even keel, only occasionally priming the body for fight or flight. Overactive or underactive stress responses may stem from slight differences in these genes.
Life experiences may increase your sensitivity to stress as well. Strong stress reactions sometimes can be traced to early environmental factors. People who were exposed to extremely stressful events as children, such as neglect or abuse, tend to be particularly vulnerable to stress as adults.

[erinkj]

Mary, I could not sleep so, I did some searching and found several links that may be of interest to you. Most of the links are for adrenal fatigue/hypoadrenia but, toward the bottom I pasted a section of info on serotonin level and IBS also provided the link to the home page of the IBS site where I found that info. I hope this is of use to you. It was great talking to you last night and I hope you feel better today. I look forward to talking again soon. Hang in there...Love and hug's...Erin

http://www.drlam.com/a3r_brief_in_do...al_fatigue.cfm

http://www.drrind.com/scorecardmatrix.asp

http://www.womentowomen.com/adrenalfatigue/default.aspx

http://www.project-aware.org/Resourc...lfatigue.shtml

http://en.wikipedia.org/wiki/Hypoadrenia

http://adrenalfatigue.wordpress.com/...l-stress-test/

Serotonin levels and IBS

Serotonin is a chemical neurotransmitter, which means that it transmits nerve impulses. It is most famous as being involved in depression, because changes in the level of serotonin in the brain can affect our moods. However, serotonin is also found in the gut, where it affects the rate of intestinal motility. Abnormal levels of serotonin in the gut can result in constipation or diarrhea, depending on whether there is too much serotonin (diarrhea) or too little (constipation).

This idea is supported by the relative success of the drugs Lotronex and Zelnorm, both of which work on serotonin in the gut. Lotronex blocks the action of serotonin to decrease motility and so reduce diarrhea, and Zelnorm increases the action of serotonin to increase motility and reduce constipation.

Different types of serotonin are known by what are called "receptor subtypes", which are identified by a code which starts with "5-HT", or 5-hydroxytryptamine. The serotonin which is found in the intestines is mainly of the 5-HT3 and 5-HT4 subtypes. Lotronex targets 5-HT3 subtypes, while Zelnorm targets 5-HT4 subtypes.

Anti-depressants can also affect the 5-HT3 and 5-HT4 subtypes, and this could explain why they can reduce or increase IBS symptoms in some patients.

Source:http://www.ibstales.com/

[mdavis13]

Hi Yall

I have been reading many of the posts and I must admit I am a little scared. I took Exffexor for about 9 years after the birth of my 4th child, recently ( 3 + months ) switched to Lexapro because I could not get Effexor samples anymore ( we have no insurance ) So this past week I missed one day, skipped the next two just to see what would happen if I got off the meds. I have only had mild irritability and moodiness although last night I had a very hard time going to sleep. So here's my question after reading many of your notes, will it get worse as the days go by ? I read that someone got through the first few days ok and then after a week started to have a lot of symptoms. ( of yea I was only on 10 mg ) Should I be expecting this or if my withdrawl symptoms are only mild can I assume I will get through this with only mild withdrawl effects. I am a newbee and while I saw that auntie asked us to read through the whole blog so she didn't have to repeat herself I was getting a little nervous reading all the really difficult withdrawl symptoms some were having and did not want to put ideas in my head. Any help will be appreciated. Thanks yall

[oliviaj]

Originally Posted by erinkj

I just knew you would love the pottery it is such a relaxing and calming activity. When I work with clay, it seems as if the whole world just slips away and my mind relaxes! I have been busy gardening this summer, I have always loved planting gardens but, in recent years was unable to because I was renting..This year I am back to planting my veggies and feeding the bird's...and I love it. Yoga is so good for you, thumbs up to you for doing that. I used to do yoga at home (did for many years) but, I haven't since the whole lex debacle began. I want to join a yoga class but none are available in my area at this time. The YMCA told me they will be starting one this fall so, maybe I can go then. Good to know that you are listening to you're body and slowing down. To many people try to push through their problems, don't slow down and that just makes things worse. I am glad that you did not rush getting back to work and it sounds like you have a great plan. It will be wonderful for you to be able to work at your own pace and schedule....Don't rush it, you will get back to it when you are ready . Do you take milk thistle? it will detox your liver beautifully. Unless that is one you cannot process? My brother-in-law has hep C and had to do interfuron treatment. He started taking milk thistle twice a day after treatment and 3 months later his liver enzymes are looking real good...much better than his dr expected. Surprisingly, my husband told him to take it and his dr agreed but, the dr never expected it to do such a good job....Go figure! If you find the time, could you please post again about your experience of learning about your enzyme deficiency? There have been some folks who have had problems and questions about that in recent months. If you could post some about the types of testing you had and how they test that etc, that would be so helpful to many. I am so glad that you got better even though you are having some problems now...Glad you recovered from the lexapro...Hug's to you Olivia...Erin

Hi Erin, I would be happy to share my story. I will try to make it as short as possible, but it's rather complicated. As I have said before, I am a therapist. I have seen many people who were victims of sexual abuse, as was I. I decided last summer as a favor to myself and everyone I see, that I needed to process my own issues, so I went to a therapist that I trust. By the end of the summer I had decided that I needed to speak to the person that had done the abuse and I was very nervous. I couldn't shake it. When I saw my family doc for something else but told him what was going on he suggested lex to "get me over the hump." I did not respond well, had almost a paradoxical effect, which is to say I got MORE nervous. I decided it was a dumb idea and quit after 2 weeks. When I went back to the doc so he could see how I was doing on the lex and I told him I had quit, he put me on propanolol to stop the side effects of the lex. I started becoming very ill after only one week on the propanolol. I was getting adrenaline rushes, nausea, stomach cramping, weakness, loss of appetite, etc. I talked to his nurse and she said to "soldier on", that that would pass. She said definitely not to stop it or I could get bad rebound side effects. After 3 weeks, I called my daughter who is a psychiatry resident and said help, I feel awful. We assumed it was still side effects from the lex. She sent me to a good doc that she knows who is good with psychopharmacology and she immediately said I think it's a liver enzyme problem. She wrote a script for cytochrome P450 blood test, checking 2C19 (where lex is metabolized) and 2D6 (propanolol). It was done at a lab in my town and sent to the Mayo Clinic. However, when it came back, no one really knew how to read the results. It had now been a month, and I was getting sicker by the day. I ended up in the ER with elevated blood pressure and heart rate, but all my tests came back fine. By this time, half my hair had fallen out, I was so weak I could only stand for 10 minutes at a time, and I was as white as paste and had lost 20 lbs, which I couldn't afford. I knew I was dying, but of what, I did not know. I called my doc who said I was depressed and should see a psychiatrist. He didn't even listen to my liver enzyme story. I took it for 2 more weeks as I was looking for a new doc, and my husband finally made me quit. He told me I would be dead soon if I didn't stop, no matter what my doc said, and I knew it to be true, so I quit. I took me 2 more months to find Dr. David Flockhart who is the Chief of Clinical Pharmacology at the Indiana University School of Medicine and an expert in pharmacogenomics. He agreed to see me at the end of Jan. and I went down there with my husband and duaghter. I need to interject that I grew up in a homeopathic family so have taken very little meds in my lifetime, which, it turns out, is a blessing. He looked at my test results and said that I have no activity at all on the 2D6 enzyme so my liver was not damaged because it never hit my liver. There are 2 alleles for every genetic trait and both of mine (*2 and *4) are nonfunctioning alleles. He said I was lucky to be alive and had at least 10x the normal concentrations in my body. He said after it bypassed the liver it went straight to my brain, muscles, fat cells, etc. I had (and still have) central nervous system toxicity along with very disorganized muscle activity which causes spasms everywhere, particularly the gut(causing nausea and setting up good conditions for an ulcer), but I twitch everywhere. I also hurt all over a lot. The worst is the cns toxicity, because I still don't feel like I have my own brain back. I live with a lot of adrenaline. I won't even call it anxiety, because I don't get anxious, it's just SO wearing on you. And the bad, bad dreams. Yuk. Anyway, all of you out there. Please take this very seriously. I almost died. I'm not sure why I didn't. Dr. Flockhart told me that just 2D6 enzyme problems alone (not counting the other 5 or 6 enzymes) account for 10-15% of the population with over 30 million in the US alone being affected. My son and grandson have been tested since I got tested and both are intermediate metabolizers, which means they have one functioning allele and one of my nonfunctioning ones. This means if they ever had to take a 2D6 med, they would have to take much less than a normal person because they can only process a portion of it. If this had not been detected and they had taken normal amounts, they could have destroyed their livers, and of course died. Please go to Dr. Flockhart's website drug-interactions.com if you suspect a problem and try to isolate which enzyme is giving you the problem by looking at which meds you've had trouble with. This helps the doc, because it is too expensive to test all of them. Thanks for listening. Olivia

[Aeroman]

Well, I am into 5 1/2 months since my last 10mg Lexapro pill after 2.5
years of use and a fantastic 1-month taper that my shrink had me do.
No new update. I am still feeling somewhat lightheaded, low back
pain, depression, anxiety and some restlessness. All I want to do is
go home, lay down, and simply close my eyes. I would love some
improvement from this but I understand it will be gradual. The Phase
2 emotional symptoms started at the end of Month 3, beginning of Month
4 for me. I thought it was a return of my anxiety/depression but
somehow this isnt the same...this feels more intense. Its kinda hard
to explain. I find it much more difficult to do ANYTHING. And I am
sensitive to mild anxiety attacks (i.e. I watched the new Batman movie
and I had a surge of adrenaline there!).

Hang in there everyone...

[auntybiotic]

I spoke to Mary/Ivy'sphotomom and she wanted me to let you know that she was going to the ER and may not be able to get back to you for a day or so. Keep her in your prayers. She has nausea and flu like symptoms.

aunty

[auntybiotic]

Originally Posted by mdavis13

Hi Yall

I have been reading many of the posts and I must admit I am a little scared. I took Exffexor for about 9 years after the birth of my 4th child, recently ( 3 + months ) switched to Lexapro because I could not get Effexor samples anymore ( we have no insurance ) So this past week I missed one day, skipped the next two just to see what would happen if I got off the meds. I have only had mild irritability and moodiness although last night I had a very hard time going to sleep. So here's my question after reading many of your notes, will it get worse as the days go by ? I read that someone got through the first few days ok and then after a week started to have a lot of symptoms. ( of yea I was only on 10 mg ) Should I be expecting this or if my withdrawl symptoms are only mild can I assume I will get through this with only mild withdrawl effects. I am a newbee and while I saw that auntie asked us to read through the whole blog so she didn't have to repeat herself I was getting a little nervous reading all the really difficult withdrawl symptoms some were having and did not want to put ideas in my head. Any help will be appreciated. Thanks yall

Hi,

Not to alarm you but you may feel worse with each passing week. Ten milligrams of lexapro is the normal dose that most take. You may feel dizziness, brain zaps/electric like discharges that run from brain to extremeties, nightmares, crying jags, sweats then shivering and flu like symptoms, sinus issues like a sinus infection and the runs and stomach cramping.

The third month of cold turkeying off lexapro or tapering fast you may experience a depersonalization and withdrawal from friends and family....this is all normal withdrawals.

You may be one of the rare lucky ones that get by with few withdrawals. Wait and see and if you begin getting the above mentioned withdrawals .you can always choose to reinstate the lexapro and taper off by 5% increments every three weeks.

aunty

[ShouldBeAShrink]

Welbutrin is the worst medicine I've ever been on. I was prescribed it with the Paxil CR 25mg because it was supposed to help with the sexual side effects from Paxil. The first two weeks I was on 100mg then it was upped to 300mg. The first two weeks I took it I was fine, I even felt like I had more energy when I got up in the morning, then I tried the 300mg and even though I had the Paxil CR and the Klonopin, I was jumping out of my skin. The doc said the Paxil CR would keep the anxiety at bay and the Welbutrin wouldn't cause any anxiety. I almost cussed him when I went back later that month for him to see how I was doing. I flushed the pills down the toilet and just stayed with the Paxil and bought a big bottle of KY and called it a day for that one. I would rather deal with the sexual side effects than go through that again. It was a different feeling than a panic attack. I guess because I wasn't on it that long and that I was also on the Paxil I didn't have any withdrawal effects from the Welbutrin but that is something I will never try again. I am no doctor, but I don't think any antidepressant combined with Welbutrin will make anyone feel better or help cure sexual side effects which at the time when it came out, that was the big thing for everyone to try to help with that. The thought of being on it, freaks me out. BLEH!

[erinkj]

Originally Posted by auntybiotic

I spoke to Mary/Ivy'sphotomom and she wanted me to let you know that she was going to the ER and may not be able to get back to you for a day or so. Keep her in your prayers. She has nausea and flu like symptoms.

aunty

Thanks alot for letting me know. I would have worried. She was feeling a bit better when I spoke to her last night but, I told her she should get checked out if all the symptoms continued or got worse. I will keep her and you, both in my prayers. I am glad that she went in and I hope she get's some answers. God Bless...Erin

[erinkj]

OliviaJ: Thanks for posting your experience. I just know that will be helpful to many. The link to your dr's website....WOW....a fountain of info available there, thanks for posting it.

Shouldbeashrink: I agree 100% about the wellbutrin. It makes you fell like you are shaking on the inside and jumping out of your skin...I tried zyban (aka:bupropion same chemicle as wellbutrin) many years ago to try to quit smoking...UGH...freaky stuff. People with anxiety should NOT take that med, it is far to stimulating.


Just a side note about med cocktails. As terrible as this may come off sounding, I admit that I feel fortunate to only be dealing with getting off of two med's. When my symptoms get real bad I look at my husbands med cocktail and count my blessings! I catch myself thinking, WOW, My problems are not so bad, they could be much worse, I could be on all the stuff he takes....Perhaps that is insensetive of me but, still, I will take my med's over his ANY DAY! Just to show you all how far out of hand psychiatrists can get with med's, some to treat and some to counteract side effects, I will list my hubby's med's and see how many eyeballs pop out ....
Clonodine for BP (is a calcium channel blocker also effects brain chemicls)at bedtime
Depakote ER 500 mgs at bedtime
klonopin 2 mgs at bedtime, 1 mg in the morning and 1 mg afternoon.
Cymbalta 40 mgs in the morning
Wellbutrin 100 mgs in morning. (he is supposed to up to 300 mgs but, don't think he will)
Dr just replaced stratera with the wellbutrin 2 wks ago.
Testosterone cream for HRT (don't remember dose) every morning.
Lunesta 2mgs at bedtime ( he rarely takes this one anymore)
Immitrex injections as needed.

Every single medication that he is on interact with each other and could easily cause serotonin syndrome at any time. The most he has been cautioned about any of this is from me of course, and his psych said that if he has to use the immitrex then he should skip his cymbalta the next day. At one point 5 months ago, he was on 12 mgs xanax a day with oxycodone for pain after back surgery....Doctors were all aware of his med's and not one even blinked over it. Except the shrink, she freaked about the xanax and got him switched over to klonopin which he is now tapered down to 4mgs a day. With all these med's it is very difficult to isolate what is helping and what is causing which side effects...strangely enough he has not had ANY sexual side effects at all...I atribute that to the test cream....In competition over who has more brain cooties, I bow down and hand him the crown....(personal joke)..Anyway, you all get the idea of what dr's will do.....We have already decided on our plan to eliminate his med's one at a time...Long road ahead for us both...Hang tight everyone...It could always be worse...Peace...Erin

[auntybiotic]

These are interesting links. Many people cannot metabolize SSRI antidepressant meds and therefore have bad side effects and much difficulty tapering off. Many years ago I wrote in depth about this but I will repost as this forum is in excess of 250 pages. Please read as this is VERY important!

http://www.erowid.org/psychoactives/...enzymes1.shtml

http://www.uspharmacist.com/oldforma...article_id=704

http://www.dextroverse.org/Archives/...teractions.pdf ***ERIN, This article is a must read after seeing the list of your husband's meds.
Please take a moment to read as this info is very valuable and could possibly prevent serotonin syndrome.

aunty

[auntybiotic]

I have added a link to a book on SSRI's and the P 450 Cytochrome Sytem. Save it and read it when you get a chance. It will help many not realizing how important the liver is in the metabolizing of Lexapro and how foods and other drugs can interupt the process.

http://www.ahrq.gov/downloads/pub/ev...450/cyp450.pdf

Save it to your favorites as it is very important.
aunty

[auntybiotic]

Specific Pharmacokinetic Features of Psychotropic Medications



Antidepressants SSRIs

Citalopram( Same as Lexapro for pharmacokinetic features)
Citalopram is metabolized primarily by P450 2C19, 2D6, and3A4.31–33 It is likely a mild to moderate inhibitor of 2D6,31,34 as evidenced by its ability to increase blood levels of desipramine and metoprolol.35 Citalopram is a substrate of P-glycoprotein.36

Escitalopram/lexapro
The pharmacokinetic features of escitalopram are basically the same as those of citalopram.37,38

Fluoxetine (norfluoxetine)
Fluoxetine and its active metabolite norfluoxetine are together metabolized by P450 2C9, 2C19, 2D6, and 3A4.15,39 Together, they potently inhibit 2D634,40 and mildly to moderately inhibit 1A2, 2B6, 2C9, 2C19, and 3A4.41–46 Fluoxetine can reasonably be considered a P450 pan-inhibitor, much like cimetidine. It is also a P-glycoprotein inhibitor.47

Fluvoxamine
Fluvoxamine is primarily metabolized by P450 1A2 and secondarily by 2D6.48,49 It is a pan-inhibitor like fluoxetine. It is a potent inhibitor of 1A2 and 2C19,45,48,50 and a mild to moderate inhibitor of 2B6, 2C9, 2D6, and 3A4.34,42,43,45,50,51 It is also both a substrate and an inhibitor of P-glycoprotein.47,52

Paroxetine
Paroxetine is primarily metabolized by P450 2D6 and secondarily by 3A4.45,53 It is a potent inhibitor of 2B6 and 2D634,42,54,55 but only a mild inhibitor of other P450 enzymes.41,44 It is also both a substrate and an inhibitor of P-glycoprotein.47

Sertraline
Sertraline and its mildly active metabolite desmethylsertraline are substrates of multiple P450 enzymes.56,57 Sertraline inhibits 2D6 in a dose-dependent manner. At doses under 100 mg/day, sertraline may only mildly inhibit 2D6. At doses above 150 mg/day, 2D6 inhibition may become moderate to potent.34,58 Sertraline is also a moderate inhibitor of 2B6 and 2C1942,44 and a mild inhibitor of 1A2 and 3A4.41,59–61 Possibly unique among the SSRIs, sertraline also appears to be a specific and potent inhibitor of UGT 1A4, as evidenced by the ability of 25 mg/day of sertraline to double the blood level of lamotrigine.62 Sertraline is also a P-glycoprotein inhibitor.47

Tricyclic Antidepressants
Secondary amine tricyclic antidepressants
Secondary amine tricyclic antidepressants (TCAs), including desipramine, nortriptyline, and protriptyline, are primarily substrates of P450 2D6, which performs hydroxylation on these compounds.20,21,63–66 They are also moderate 2D6 inhibitors.34,67,68 These TCAs also appear to be inhibitors of P-glycoprotein, and nortriptyline has been demonstrated to be a P-glycoprotein substrate.69–72

Tertiary amine TCAs
The metabolism of tertiary amine TCAs, including amitriptyline, clomipramine, trimipramine, imipramine, and doxepin, is much more complex than that of the secondary amine TCAs. Tertiary amine TCAs undergo both demethylation to secondary amine TCAs through the action of 1A2, 2C19, and 3A4 and hydroxylation by 2D6.63,65,73–77 UGT 1A4 also makes a minor contribution to the metabolism of tertiary amine TCAs.23,78,79 Tertiary amine TCA inhibition of 2D6, considered without the contribution of the secondary amine metabolites, tends to be only mild, and there is some evidence that amitriptyline and imipramine are mild inhibitors of 2C19.68 These TCAs also appear to be both substrates and inhibitors of P-glycoprotein.69–71,80,81

Other Antidepressants
Bupropion
Bupropion is primarily metabolized by P450 2B6.82,83 It is a moderate to potent inhibitor of 2D6.84,85

Duloxetine
Duloxetine is metabolized by P450 1A2 and 2D6.37,86 It is a moderate inhibitor of 2D6.86,87

Mirtazapine
Mirtazepine has multiple metabolic pathways, including metabolism by P450 1A2, 2D6, and 3A4.88,89 It has no significant inhibitory or inductive capabilities.90

aunty

[auntybiotic]

Perspectives on Psychopharmacology: Drug Interactions: A Tangled Web We Weave (Part I)
By Neil Sandson, M.D.

[Winter 2004; Vol. 30, No. 2; Pg 4, 9]

Psychopharmacology is a complex undertaking. As the array of available medications continues to grow, it becomes ever more difficult to remain familiar with their properties. It poses even more of a challenge to the busy psychiatrist to master the domain of drug interactions. This task requires that one become familiar with the metabolism of the agents we prescribe, as well as those metabolic pathways whose function is enhanced or impaired by these same medications. This is quite a daunting task, and yet it is an essential one if we are to remain true to the dictum, “First, do no harm.”

As our understanding of drug metabolism has increased over the years, we have learned a great deal about the physiologic elements which mediate drug interactions. Probably the most important of these is the Cytochrome P450 System, a family of mostly hepatic enzymes that perform oxidative (phase I) metabolism on most of the drugs we prescribe. The main P450 enzymes are 1A2, 2C9, 2C19, 2E1, 2D6, and 3A4. Substrates are those agents which are metabolized by particular P450 enzymes. Inhibitors impair the ability of specific P450 enzymes to metabolize their target substrates, thus producing increased blood levels of those substrates. For example, when the 2D6 inhibitor paroxetine (Paxil) is added to the 2D6 substrate propranolol (Inderal), this impairs the ability of 2D6 to metabolize the propranolol. This could manifest clinically as bradycardia, hypotension, and even syncope. Conversely, inducers cause an increase in the production of particular P450 enzymes, leading to increased metabolism of substrates by that P450 enzyme. For example, the addition of the 3A4 inducer phenytoin (Dilantin) to the 3A4 substrate quetiapine (Seroquel) may increase the clearance of quetiapine up to fivefold (and decrease blood levels tenfold), leading to subtherapeutic blood levels of quetiapine. A comprehensive P450 table is available through Dr. David Flockhart’s website, www.drug-interactions.com.

Let’s consider some brief case examples:

Case 1: A 72 year-old female with type II diabetes mellitus and atrial fibrillation had been receiving warfarin (Coumadin), 5 mg/d (INR = 2.9) and amitriptyline (Elavil), 50 mg qHS for neuropathic pain. When she developed a major depression, fluoxetine (Prozac), 20 mg/d was added to her regimen. Over the next 10 days, she experienced increasing dizziness, dry mouth, and inability to void. She eventually required transportation to an ER. Once there, a bladder catheterization yielded 2 liters of dark urine and her INR was found to be 17.3.

Discussion: This is an example of an inhibitor added to two substrates, whose effects synergized to produce the complications described above. First, warfarin’s metabolism mostly occurs at 2C9. Fluoxetine (in concert with its active metabolite, norfluoxetine) is a strong 2D6 inhibitor and a moderate inhibitor of 2C9, 2C19, and 3A4. Thus, the addition of the fluoxetine significantly impaired the ability of 2C9 to efficiently metabolize the warfarin, which led to an increase in the warfarin blood level, even though the warfarin dose remained unchanged throughout. This drastically increased the magnitude of the warfarin’s anticoagulant effect. Second, amitriptyline is a tertiary amine tricyclic antidepressant (TCA) whose metabolism depends mostly on the intact functioning of 2D6, 3A4, and 2C19. As above, fluoxetine+norfluoxetine significantly impaired the ability of 2D6, 3A4, and 2C19 to metabolize amitriptyline, which led to an increase in the blood level of amitriptyline + nortriptyline. The resultant increase in anticholinergic tone led to the inability to void and subsequent bladder wall distension. These combined effects of a hypocoagulable state and anticholinergic-induced urinary retention led to spontaneous bleeding within the patient’s distended bladder.

Case 2: A 25 year-old male’s psychotic mania was adequately stabilized with olanzapine (Zyprexa), 20 mg/d on a non-smoking inpatient unit, and he was then discharged on that dosage of olanzapine. He normally smoked 2 packs of cigarettes per day which he resumed after discharge. Despite strict compliance with his medication, he was readmitted within 3 weeks due to a relapse.

Discussion: This is an example of an inducer added to a substrate. Olanzapine is a 1A2 substrate, although it is also metabolized by 2D6 and phase II glucuronidation. Tobacco use, via cigarette smoking, is a significant 1A2 inducer. When the patient resumed smoking, this significantly increased the amount of 1A2 available to metabolize the olanzapine, resulting in a decrease in the blood level of olanzapine. Studies have demonstrated that smoking may increase the clearance of olanzapine by as much as 40%. Therefore, the patient’s smoking produced clinical decompensation severe enough to necessitate his readmission to the hospital.

Case 3: A 65 year-old male with GERD and depression had been successfully treated with doxepin (Sinequan), 75 mg qHS (blood level = 225 ng/mL) and cimetidine (Tagamet), 300 mg q.i.d. He began to experience increased heartburn, prompting him to visit his internist, who discontinued his cimetidine and started him on pantoprazole (Protonix). Within 5 weeks, the patient became desperately depressed, overdosed on tylenol, and required psychiatric hospitalization. A doxepin blood level performed on admission was only 104 ng/mL.

Discussion: This is an example of reversal of inhibition. Doxepin is a tertiary amine TCA whose metabolism depends mostly on the intact functioning of 2D6, 3A4, 2C19, and 1A2 in a manner similar to imipramine. Cimetidine is a potent pan-inhibitor of all major P450 enzymes except for 2E1. The discontinuation of the cimetidine led to an increase in the metabolism of the doxepin lowering its blood level, even though the dose had not been changed. Removal of the inhibitor (cimetidine) led to a loss of antidepressant efficacy, culminating in a recurrence of depression and an overdose attempt.

The complexity of this topic begs the question: How is one to keep up with all of this? Here are some drug interaction survival tips: 1) Become especially familiar with the properties of those medications which you prescribe or otherwise encounter on a regular basis. 2) Pay special attention to those agents with a low therapeutic index (LD50/ED50), such as digoxin, lithium, and tricyclic antidepressants. 3) Refer frequently to helpful tables, charts, drug interaction computer programs (such as ePocrates Rx ProTM, MICROMEDEX, Lexi-InteractTM, and the program of Dr. Jessica Oesterheld and Dr. David Osser at www.mhc.com/Cytochromes), and websites such as www.drug-interactions.com. 4) Encourage your patients to obtain all of their medications from the same pharmacy and ask them to enroll in that pharmacy’s drug interaction monitoring program, as this may not happen automatically at some commercial pharmacies. 5) Whenever possible, select agents with less of a propensity to interact with other medications. For instance, among the selective serotonin reuptake inhibitors, Citalopram (Celexa) and escitalopram (Lexapro) lack the ability to significantly inhibit any of the P450 enzymes. 6) There are books which address these topics. They are available through the American Psychiatric Press, Inc. (www.appi.org).

[auntybiotic]

PHARMACOKINETICS: Peak plasma levels of escitalopram occur 3 to 6 hours after single oral doses. The drug has a volume of distribution of about 12 L/kg, a clearance of 600 mL/min, and an elimination half-life of approximately 29 hours. It is metabolized extensively in the liver via the cytochrome P450 enzyme system to S(+)-desmethylcitalopram and S(+)- didesmethylcitalopram; these are 7 and 27 times less potent than the parent compound, respectively (In vitro data). Less than 10% of an oral dose of escitalopram appears unchanged in the urine.
Lexapro is metabolized primarily by P450 2C19, 2D6, and3A4.It is likely a mild to moderate inhibitor of 2D6,31,34 as evidenced by its ability to increase blood levels of desipramine and metoprolol.


Use caution taking other drugs metabolized by same pathways while trying to taper off lexapro as more severe withdrawals or serotonin syndrome may occur..

aunty

[auntybiotic]

P450: Enzymes With the Answers on Drug Risks

By David Brown
Washington Post Staff Writer

If you think p450 3A4, and its brothers 2D6 and 2C19, are cute little robots from the next "Star Wars" movie, you can be forgiven. Ten years from now, however, you might not make the same mistake.

P450 is the name of a family of enzymes crucial to the human body's ability to metabolize--or burn off--drugs. Discovered in 1958, the p450 enzymes were barely known outside the world of research pharmacology for three decades. In 1990, however, their importance in the shadowy world of drug side effects and interactions burst into public view, taking down the nation's fifth-best-selling drug in their wake.

Today, knowledge of the p450 enzyme system is changing the way drug companies develop drugs, the way the government approves them, and the way doctors prescribe them. The day may not be far off when people know their p450 profiles the way they know their blood types.

Drug metabolism was once an arcane subject beyond the worry of physicians and patients. That time is no longer. Americans take more medicine than any people in history. The average person gets prescriptions for eight different pharmaceuticals each year. A 1997 government survey found that 36 percent of people who visited doctor's offices were prescribed two or more drugs. Five percent got five or more.

Taking a single drug exposes a person to its side effects. Taking two introduces not only each substance's potential side effects, but also the risk of interactions between them. For mathematical reasons, the risk rises steeply when a person is taking three or more drugs.

The p450 enzyme system is not the key to understanding all "drug-drug" interactions. But it's a major window on some of the more important and hard-to-predict ones.

The formal name for the enzymes is "cytochrome p450 oxygenases." They're sometimes abbreviated CYP, followed by a specific enzyme designation, as in CYP3A4. The p stands for protein, the 450 for the 450-nanometer wavelength of light they absorb, which is part of their chemical signature.

As all enzymes do, the p450s promote specific chemical reactions that, without them, would occur too slowly to be of use to living things. More than 700 kinds of p450--each with its own gene carrying instructions for its production--have been found in animals, plants, fungi and bacteria. Some evolutionary biologists believe, in fact, that because p450s are so widespread, they will be a major tool in eventually drawing the definitive "tree of life" that will outline the kinship relationships of all living things.

Human beings have about 50 different p450 enzymes. Some are involved in the synthesis of complicated hormones (such as estrogen and testosterone) from simpler compounds. Their more important work, however, is in the break-up and detoxification of substances arriving from the outside, mostly through food.

One of the many insights of the last decade is that scientists can't reliably count on laboratory animals to show them how new drugs will interact with human p450 enzymes. That's because each species--to some degree, at least--has a collection of p450s tailor-made for its diet and environment. Although mice and men have much in common, those are two realms in which they don't.

There are now ways to determine, using yeast that contain human genes, whether a chemical compound is detoxified by p450 enzymes in people, and if so, by which ones. The Food and Drug Administration requires that all drug "candidates" be screened for those properties long before they go on the market.

That wasn't true, however, in December 1989, when a 39-year-old woman walked into the emergency room of the National Naval Medical Center in Bethesda after fainting at the dinner table.

She was taking terfenadine, a best-selling antihistamine sold under the trade name Seldane. After she was admitted to the hospital, an EKG monitor recorded a life-threatening rhythm when she fainted again.

Louis R. Cantilena, a physician and pharmacologist at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, was called in for advice. He knew the heart rhythm was one often caused by drugs. He queried the woman further, and she added a crucial detail.

Several days earlier she had felt a vaginal yeast infection developing and had taken a couple of tablets of ketoconazole, an antifungal medicine, left over from an old prescription. Cantilena knew that ketoconazole was a potent inhibitor of some p450 enzymes. (In fact, that's how it works, by blocking the enzymes in fungus cells.) After she went off the drug, her EKG returned to normal.

"She actually turned out to be a very lucky woman," Cantilena recalled last week. "She spontaneously converted [to a normal heart rhythm] from four of these episodes and survived. Many like her did not survive."

Much of the work that followed was done in the Washington area--at USUHS, Georgetown University and the FDA. Researchers determined that ketoconazole blocked p450 3A4. That allowed terfenadine--normally rapidly metabolized into another compound that actually functioned as the antihistamine--to build up in the blood. A Georgetown scientist, Raymond L. Woosley, determined that unmetabolized terfenadine blocked a specific "ion channel" in heart tissue, changing its function.

By May 1992, the FDA had learned of 83 serious cardiac events, including 15 deaths, associated with interactions between terfenadine and a growing list of p450 3A4-inhibiting drugs. Various drug label warnings and letters to doctors reduced this "co-prescribing" significantly, but not enough to eliminate the problem. The drug was eventually taken off the market.

Terfenadine wasn't alone. In recent years, three other drugs have been withdrawn because of p450-related risks.

The latest occurred last month, when Janssen Pharmaceutica announced it would stop making cisapride, an anti-heartburn drug sold as Propulsid. Propulsid topped out in 1995 as the country's 54th-best-selling prescription drug, according to the tracking firm IMS Health. It had been implicated in 341 reports of heart rhythm abnormalities, including 80 deaths.

Pharmacologists now know there are four potential problems involving p450 enzymes.

Some drugs are metabolized by only one or two of the enzymes, and consequently are subject to climbing to toxic levels if those enzymes are blocked. Some drugs block specific enzymes. A few drugs actually turn up specific p450s, speeding the body's ability to burn off certain compounds. (A list of important p450 drug interactions is available at http://dml.georgetown.edu/depts/phar.../clinlist.html.)

The fourth and trickiest problem is that sizable fractions of different ethnic groups lack certain p450s altogether. This means a lot of people are subject to potentially disastrous drug toxicity and don't know it. Pharmaceutical companies now look for this problem early.

Two years ago, Merck Research Laboratories discovered that one of the COX-2 inhibitors ("super aspirins") it was working on was metabolized primarily by p450 2C19. That enzyme is missing in about 22 percent of Japanese.

"We did not continue that developent program, but rather switched to another compound that didn't have that liability," said Thomas A. Baillie, the company's vice president for drug metabolism.

[auntybiotic]

Lexapro increases your cortisol by double.


Adrenal fatigue — the effects of stress and high cortisol levels
by Marcy Holmes, Women’s Health NP, Certified Menopause Clinician

Here are the topics covered in this article:

The role of healthy adrenal glands
How chronic stress causes adrenal exhaustion
The effects of adrenal fatigue — cortisol and DHEA
Should you have your adrenals tested?
Restoring adrenal health naturally
Our patients’ most common symptoms are fatigue, insomnia, weight gain, and depression. Does that sound like you? If so, your underlying problem may be adrenal fatigue.

Every woman who comes to our clinic with these symptoms gets an adrenal fatigue test, which consists of a series of tests of cortisol levels. And the results — in over thousands of cases — are remarkably consistent: only 1% have cortisol levels indicating healthy adrenal function, while 99% suffer impaired function, ranging from significant adrenal stress to complete adrenal exhaustion.

The effects of adrenal dysfunction can be profound: fatigue and weakness, suppression of the immune system, muscle and bone loss, moodiness or depression, hormonal imbalance, skin problems, autoimmune disorders, and dozens of other symptoms.

The good news is that adrenal fatigue can almost always be relieved. Let’s look at the relationships between stress, high cortisol levels and adrenal fatigue, and then we’ll look at how you can give your adrenals more support.

The original, life-saving role of the adrenal glands

To understand how adrenal fatigue develops, it is important to understand the original, evolutionary function of the adrenal glands. The adrenals are walnut-sized glands located on top of each kidney, and are important control centers for many of the body’s hormones. The outer layer of the gland, called the adrenal cortex, produces hormones including cortisol, DHEA, estrogen and testosterone. The centers of the glands produce adrenaline, the hormone named after them.

The basic task of your adrenal glands is to rush all your body’s resources into "fight or flight" mode by increasing production of adrenaline and other hormones. When healthy, your adrenals can instantly increase your heart rate and blood pressure, release your energy stores for immediate use, slow your digestion and other secondary functions, and sharpen your senses.

Let’s emphasize two points about this healthy stress response. First, it takes priority over all other metabolic functions. Second, it wasn’t designed to last very long.

Stress and the adrenal glands
Unlike our ancestors, we live with constant stress. Instead of occasional, acute demands followed by rest, we’re constantly over-worked, under-nourished, exposed to environmental toxins, worrying about others — with no let-up.

Every challenge to the mind and body creates a demand on the adrenal glands. And the list of challenges is endless: lack of sleep, a demanding boss, the threat of losing your job, financial pressures, personality conflicts, yo-yo dieting, relationship turmoil, death or illness of a loved one, skipping meals, reliance on stimulants like caffeine and carbs, digestive problems, over-exercise, illness or infection, unresolved emotional issues from our past or present and more. The result is adrenal glands that are constantly on high alert.

The destructive effect of high cortisol levels

What is cortisol? In its normal function, cortisol helps us meet these challenges by converting proteins into energy, releasing glycogen and counteracting inflammation. For a short time, that’s okay. But at sustained high levels, cortisol gradually tears your body down.

Sustained high cortisol levels destroy healthy muscle and bone, slow down healing and normal cell regeneration, co-opt biochemicals needed to make other vital hormones, impair digestion, metabolism and mental function, interfere with healthy endocrine function; and weaken your immune system.

Adrenal fatigue may be a factor in many related conditions, including fibromyalgia, hypothyroidism, chronic fatigue syndrome, arthritis, premature menopause and others. It may also produce a host of other unpleasant symptoms, from acne to hair loss. (Please click here to see a list of adrenal fatigue symptoms and related conditions.)

The loss of DHEA production
When the adrenals are chronically overworked and straining to maintain high cortisol levels, they lose the capacity to produce DHEA in sufficient amounts. DHEA (the full name is dehydroepiandrosterone) is a precursor hormone to estrogen, progesterone, and testosterone, and is necessary to moderate the balance of hormones in your body. Insufficient DHEA contributes to fatigue, bone loss, loss of muscle mass, depression, aching joints, decreased sex drive, and impaired immune function. (For more information, read our article on DHEA.)

Testing for adrenal fatigue
Conventional medicine is truly wonderful at treating disease-state conditions. Unfortunately its focus on drugs also tends to suppress early-stage symptoms rather than treat their underlying causes. This can have the effect of delaying treatment until a disease state has developed. This is true in the case of adrenal fatigue cortisol testing. In the conventional standard of care, any cortisol level within a very broad range is considered normal, and anything outside that range indicates disease.

In our practice, we measure cortisol levels at several points in the day to track the adrenals’ day–night pattern (called the “diurnal rhythm”) using a panel of simple saliva tests. We hope to see cortisol elevated in the morning to help you get going, lower but steady throughout the day to sustain energy, then fall in the evening to support restful sleep.

In the early stages of adrenal dysfunction, cortisol levels are too high during the day and continue rising in the evening. This is called “hyperadrenia.” In the middle stages, cortisol may rise and fall unevenly as the body struggles to balance itself despite the disruptions of caffeine, carbs and other factors, but levels are not normal and are typically too high at night. In advanced stages, when the adrenals are exhausted from overwork, cortisol will never reach normal levels (“hypoadrenia”).

Conventional medicine will detect only the extremes of these conditions, when damage to the adrenals has already occurred (Cushing’s disease and Addison’s disease). Within those extremes, you can feel miserable and still be told your cortisol levels are normal. But by responding to early-stage symptoms of adrenal fatigue, we can reverse the developing dysfunction.

Should you get an adrenal test?

In general, if you feel happy and well, have steady energy and emotions, sleep soundly seven to nine hours a night, wake up feeling rested, recover well from stress, and maintain a healthy weight without dieting, then your adrenals are probably doing well.

On the other hand, if your energy lags during the day, you feel emotionally unbalanced much of the time, you sleep poorly or less than seven hours a night, can’t lose excess weight even while dieting, use caffeine or carbohydrates as “pick-me-ups” — these are all red flags indicating adrenal insufficiency.

Natural adrenal support — how to restore healthy adrenal function
The first step is to have a full physical exam to rule out disease or other factors. In our experience, women with mild to moderate cases of adrenal fatigue can see significant improvement through these steps:

Dietary changes to enrich your nutrition and reduce carbohydrates and stimulants. We also recommend the addition of high-quality nutritional supplements, including essential fatty acids from fish oil.
Stress reduction, including moderate exercise and taking more time for yourself. It’s helpful to make a list of your stressors, especially those that are constant.
Get more rest. Your body needs time to heal.
Women with more severe symptoms, or those who have reached complete adrenal exhaustion, usually need greater intervention. At our practice we use the steps outlined above with the added natural support of phosphorylated serines, low-dose compounded DHEA, ginseng, and deglycyrrhizinated licorice. We personalize the therapy to each woman’s symptoms and test results. (We urge you not to self-prescribe these substances, as they can have adverse health effects. Please click here to learn more about DHEA supplements.)

It’s important to emphasize the role of emotional factors. Guilt, pain from past hurts, self-destructive habits, unresolved relationship problems — your past and present emotional experience may serve as an ever-present stressor. Dealing with these problems directly is much more beneficial than trying to compensate for the stress they create, in the same way that "an ounce of prevention is worth a pound of cure."

In all but the most extreme cases, we expect to see dramatic improvement within about four months. For mild to moderate adrenal fatigue the turnaround can be much faster. Remember, you may feel too tired to make changes now, but by moving forward in stages, you’ll build the strength you need to stay with it. You will love how you feel when you do!

[ivysphotomom]

Just up briefly from bed....

Went to the ER last night to have some tests run.

Want to give me a call today? I unplugged my phone yesterday for a nap, and lost all my caller ID numbers!

Thanks,

~Mary


Aunty - I'll call you later too....

Things seem fairly OK, but I'm still sick...

[stonecold]

I didn't talk to anyone about it, but i ran out of my monthly. and had gonne from 20, to 10 for two weeks then just stopped.

Im anxious. but i may not be a side effect.

I would offten go into times where i didnt want to be with anyone would just go to my room and watch tv..

should this stop?

[erinkj]

ScienceDaily (Aug. 14, 2008) — Scientists have unveiled a functional link between production of new neurons and the effectiveness of antidepressants (ADs) in an animal model. The study, published by Cell Press in the August 14 issue of the journal Neuron, provides exciting insight into a mechanism that might underlie a poor response to antidepressive medications for anxiety or depression.

Depression is a significant public health problem due to both its high prevalence and its devastating impact on individuals and society," says senior author Dr. Luis F. Parada from the University of Texas Southwestern Medical Center. "Despite much excitement generated by recent advances in the knowledge of brain development and function, the mechanisms underlying the pathogenesis of depression, as well as its amelioration by AD treatment, remain poorly understood."

Animal studies have indicated that chronic treatment with ADs leads to production of new neurons in a part of the brain called the hippocampus. Exercise, such as running, which has a documented positive impact on mental health, also stimulates hippocampal neurogenesis. In both cases, new neurons arise from neural progenitor cells (NPCs) that seem to be required for the behavioral response to ADs.

Brain-derived neurotrophic factor (BDNF) is increased in the hippocampus after chronic AD treatment, has been linked with AD-like responses in several behavioral paradigms, and promotes proliferation of hippocampal NPCs. Interestingly, mutant mice with abnormal BDNF exhibit anxiety-like behaviors that are not normalized by AD treatment. Taken together, this research supports a role for BDNF in the response of the brain to chronic AD treatment.

To further investigate the relationship among BDNF, neurogenesis, and AD treatment, Dr. Parada and colleagues removed the gene for the BDNF receptor, TrkB, in a regional and cell type-specific manner. TrkB was expressed in hippocampal cells, including NPCs. Deletion of trkB in mouse embryos or adults resulted in impaired proliferation and neurogenesis in the hippocampus and prevented behavioral improvements induced by AD treatment or wheel running. Conversely, deletion of trkB from only mature neurons in the same brain regions did not impact the production of new neurons or behavioral responses to ADs.

The researchers went on to show that removal of TrkB from adult NPCs alone was sufficient to block sensitivity to chronic ADs. "Our data establish an essential cell-autonomous role for TrkB in regulating hippocampal neurogenesis and behavioral sensitivity to antidepressive treatments and support the notion that impairment of the neurogenic niche is an etiological factor for refractory responses to antidepressive regimen in mice," offers Dr. Parada.

The researchers include Yun Li, Bryan W. Luikart, Shari Birnbaum, Jian Chen, Chang-Hyuk Kwon, Steven G. Kernie, Rhonda Bassel-Duby, and Luis F. Parada, of the University of Texas Southwestern Medical Center, Dallas, TX.

[erinkj]

ScienceDaily (Mar. 26, 2008) — While analyzing data from Saskatchewan health databases, Lauren Brown, researcher with the U of A's School of Public Health, found people with a history of depression had a 30 per cent increased risk of type 2 Diabetes.

Brown then studied the medical history of 2,400 people who were diagnosed with depression and were taking antidepressants to determine whether there was a clear correlation between that disease and type 2 Diabetes.

Brown divided the group into four categories: those who took antidepressants that were considered older therapies, patients who were using newer treatments, those using a combination of both an old and new treatments and people who were switching medications.

What she found was the risk of diabetes almost doubled for the patients who were using two types of therapies at the same time, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Brown says people are usually prescribed multiple medications "if they have severe depression or if they are having a problem finding the right therapy."

Brown believes these results, and results of previous studies demonstrating an increased risk of type 2 diabetes in people with depression, emphasize the need for regular screening for type 2 diabetes in people with depression, particularly those taking more than one antidepressant. She also encourages diabetes and depression organizations to educate their members about this link.

This study was recently published in Diabetes Research & Clinical Practice.

[erinkj]

ScienceDaily (Aug. 11, 2008) — Inborn differences may help explain why trauma gives some people bad memories and others the nightmare of post-traumatic stress. Scientists in Germany and the United States have reported evidence linking genes to anxious behavior. The findings appear in the August issue of Behavioral Neuroscience, published by the American Psychological Association.

By showing that people who carry a common variation of a gene that regulates the neurotransmitter dopamine have an exaggerated "startle" reflex when viewing unpleasant pictures, the researchers offer a biochemical explanation for why some people find it harder to regulate emotional arousal. Their sensitivity may, in combination with other hereditary and environmental factors, make them more prone to anxiety disorders.

Researchers including Martin Reuter, PhD, of the University of Bonn, Germany, recruited 96 women averaging 22 years old from the Giessen Gene Brain Behavior Project, which investigates biomolecular causes of individual differences in behavior.

The researchers first determined which participants carried which variations (alleles) of the COMT gene, which encodes an enzyme that breaks down dopamine, weakening its signal. (COMT stands for a catabolic enzyme named catechol-O-methyltransferase.) Scientists call its two alleles Val158 and Met158. Depending on ethnicity, more or less half the population carries one copy of each. The rest of the population is roughly divided between carrying two copies of Val158 and two copies of Met158.

Using a well-validated psychophysiological measure, the researchers next measured the intensity of each participant's startle response by attaching electrodes to the eye muscles that, upon emotional arousal, contract and cause a blink. Participants then viewed pictures that were emotionally pleasant (such as animals or babies), neutral (such as a power outlet or hairdryer), or aversive (such as weapons or injured victims at a crime scene) -- 12 pictures of each type for six seconds each. A loud, 35-millisecond white noise, called a startle probe, sounded at random while they watched. When participants blinked, showing the startle response, a bioamplifier took readings from the electrodes and sent the information to a computer for analysis.

People carrying two copies of the Met158 allele of the COMT gene showed a significantly stronger startle reflex in the unpleasant-picture condition than did carriers of either two copies of Val158 allele or one copy of each. The two-Met carriers also disclosed greater anxiety on a standard personality test.

This finding confirms that specific variations in the gene that regulates dopamine signaling may play a role in negative emotionality. The authors speculated that the Met158 allele may raise levels of circulating dopamine in the brain's limbic system, a set of structures that support (among other things) memory, emotional arousal and attention. The researchers said that more dopamine in the prefrontal cortex could result in an "inflexible attentional focus" on unpleasant stimuli, meaning that Met158 carriers can't tear themselves away from something that's arousing -- even if it's bad.

The Met158 allele was created by a relatively recent mutation and only in the evolution of human beings. Other primate species such as chimpanzees carry only the Val/Val genotype. Co-author Christian Montag, Dipl. Psych., observes that for humans, wariness may have been adaptive. He points out, "It was an advantage to be more anxious in a dangerous environment."

A single gene variation, says Montag, can explain only a small portion of variation in anxious behavior – otherwise, in theory, up to half the population could be anxious.

"This single gene variation is potentially only one of many factors influencing such a complex trait as anxiety," he says. "Still, to identify the first candidates for genes associated with an anxiety-prone personality is a step in the right direction."

Although a great deal more research is needed, Montag says that if this line of research bears fruit, one day "it might be possible to prescribe the right dose of the right drug, relative to genetic makeup, to treat anxiety disorders."

Journal reference:

Christian Montag et al. COMT Genetic Variation Affects Fear Processing: Psychophysiological Evidence. Behavioral Neuroscience, Vol 122, No. 4

[erinkj]

ScienceDaily (Aug. 11, 2008) — CNRS and Inserm(1) researchers, working at the future NeuroCampus in Bordeaux, have just shown how one of the stress hormones regulates brain neurotransmission on the short and long term and enables neuronal connections to adapt.

This work, directed by Laurent Groc and Francis Chaouloff, may lead to the identification of new therapeutic targets for psychiatric illnesses such as post-traumatic stress disorder and depression.

When we are subjected to a stress, our adrenal glands secrete hormones that affect our entire body. One of these hormones, cortisol, enables us to adapt physically and mentally to the stimulus. Following a major or repeated stress that the individual has no control over, however, cortisol is secreted in great quantities over a long period of time. This hypersecretion has damaging effects on the individual, to the point of accelerating aging and facilitating the onset of illnesses such as depression.

The researchers have shown that in one part of the brain, the hippocampus, corticosterone (the equivalent of human cortisol in laboratory rats) modifies the intensity of transmissions made by excitatory synapses(2). To the researchers' great surprise, this hormone increases the mobility of receptors found on the surface of neurons, thus allowing synaptic connections to adapt more effectively to the demands of brain activity. The stress hormone can be thought of as an alarm that mobilizes the receptors.

In addition, briefly exposing neurons to corticosterone increases synaptic plasticity(3), due to increased receptor mobility. Although this first effect is beneficial, in the case of prolonged stress (corticosterone stimulation over several hours), synaptic plasticity is reduced. This inverse effect can be explained by the fact that after a certain amount of time, the stress hormone not only increases receptor mobility, but also increases the number of receptors mobilized at the synapse level, leading to a decrease in plasticity.

The characterization of these newly discovered mechanisms opens up numerous possibilities for future research that could enhance both fundamental knowledge and clinical benefits. We can now imagine that in certain individuals subjected to major stress, lack of receptor mobility contributes to a lack of adaptation. Under stressful conditions, synaptic plasticity would then depend on the dynamic interactions between cortisol and the neuronal receptors that modulate brain activity. In the end, better mobility means better adaptation.

Notes:

(1) Laboratoire Physiologie Cellulaire de la Synapse UMR5091 CNRS and Neurocentre U862 Inserm, Université de Bordeaux.

(2) Excitatory synapses represent more than 80% of synapses. The neurons communicate between each other at the synapse level. Broadly, this junction contains a pre-synaptic element, which sends the information, and a post-synaptic element that receives the information. When the pre-synaptic compartment is stimulated by an electrical signal, it releases chemical messengers called neurotransmitters. Then, several milliseconds later, these neurotransmitters bind to special receptors.

(3) A synapse's ability to modify the information that it transmits.


Journal reference:

Groc L., Choquet D., Chaouloff F. The stress hormone corticosterone conditions AMPA receptor surface trafficking and synaptic potentiation. Nature Neuroscience, Online July 11, 2008

[ivysphotomom]

Sorry to have left you hanging...

Did I already post here? It's been a blur...

I was in and out of the ER Friday night. Everything's turning the corner, finally. I'm working from liquids to applesauce to chicken broth...

Erin, I unplugged my phone battery one afternoon, and lost your number! Aunty, I've got yours.

My family is all down at the Outer Banks. I'm terribly lonely, and anxious. But am trying to work through it. Am about to head over to a neighbor's to visit. Maybe will sleep at home, try to watch a funny movie, and pet the cats.

Am turning a corner, in more ways than one. Just wanted you to know not to worry about me. But I am having a super hard time falling asleep. Have insomnia now, and am again nocturnal. Taking my lexpro last night at midnight did not help. I was hanging out at home with the kids, to say goodbye, and forgot earlier...fell asleep around 7am.

Anyhow, I'm really going to appreciate your company, even if via phone, this week.

Just wanted to let you know before running out, I'm OK. I saw your posts the other day, and really, really appreciated them. I've been doing a lot of praying too lately, and meditating. More on this later.

Hope you're doing well!

hugs,
~Mary

[erinkj]

Hi Mary,
I called your studio number this evening and left you a message. I left my home and cell phone numbers for you and you can call me ANYTIME that you want! I would have called yesterday but, I didn't see your previouse post until today. Then, I had a busy day so, I waited until this evening to call you. Sorry that I missed you. I really hope you'r E.R. visit provided some answers. I also hope that you are feeling better even if only a little. If I don't hear from you sooner, I will call you tomorro in the afternoon. I only have you'r studio number so, that is where I will call....Hope you can get some sleep tonight...love and hug's....Erin

[auntybiotic]

Originally Posted by ivysphotomom

Sorry to have left you hanging...

Did I already post here? It's been a blur...

I was in and out of the ER Friday night. Everything's turning the corner, finally. I'm working from liquids to applesauce to chicken broth...

Erin, I unplugged my phone battery one afternoon, and lost your number! Aunty, I've got yours.

My family is all down at the Outer Banks. I'm terribly lonely, and anxious. But am trying to work through it. Am about to head over to a neighbor's to visit. Maybe will sleep at home, try to watch a funny movie, and pet the cats.

Am turning a corner, in more ways than one. Just wanted you to know not to worry about me. But I am having a super hard time falling asleep. Have insomnia now, and am again nocturnal. Taking my lexpro last night at midnight did not help. I was hanging out at home with the kids, to say goodbye, and forgot earlier...fell asleep around 7am.

Anyhow, I'm really going to appreciate your company, even if via phone, this week.

Just wanted to let you know before running out, I'm OK. I saw your posts the other day, and really, really appreciated them. I've been doing a lot of praying too lately, and meditating. More on this later.

Hope you're doing well!

hugs,
~Mary

Hi Mary,

I hope your liver testing was OK. Good that you are able to hold down some foods. Did you have the flu on top of lexapro withdrawal?

I will be out most of the day but home after 8 PM.

Cats can be great company, they are always availabe.

Aunty

[auntybiotic]

Originally Posted by stonecold

I didn't talk to anyone about it, but i ran out of my monthly. and had gonne from 20, to 10 for two weeks then just stopped.

Im anxious. but i may not be a side effect.

I would offten go into times where i didnt want to be with anyone would just go to my room and watch tv..

should this stop?

How long were you taking 20 Mg of lexapro. had you been on any other SSRi's prior? If so what and how long.

How long ago did you stop the 10 Mg lexapro?

A lot depends on the answers to the above questions. A small percentage get by with miminal withdrawals but most do not.

Any brain zaps, dizziness, nausea, sweating, inability to fall asleep and mania? If yes then you can most likely attribute these to withdrawals. They could last from 6 months to 18 months depending on your system. Withdrawals seem to improve slowly after 6 months and may typically last up to 18 months. Everyone is different and some improve much sooner.

Are you taking any other medications, such as xanax or anything else which may be cushioning the withdrawal?

Welcome to the forum.

I am not a doctor sp please check with a physician before following any advice.

aunty

[Nocturnal]

Originally Posted by stonecold

I didn't talk to anyone about it, but i ran out of my monthly. and had gonne from 20, to 10 for two weeks then just stopped.

Im anxious. but i may not be a side effect.

I would offten go into times where i didnt want to be with anyone would just go to my room and watch tv..

should this stop?

If it's at all possible, I highly, highly, suggest that you do an extremely slow taper. This is the only way to get off the drug with minimal side effects. You should cut your 10 to 5mg and then stay on that for a month or two until you stabilize and no longer feel any withdrawal effects. From there, drop down to 2.5mg. Again, stabilize.

This is the best way to get off the drug with minimal side effects. You will be so much more happier in the mean time while you're getting off.

[wffir]

I was on it for 6 weeks,then tapered for 2.I was great for 4 weeks after I stopped,then it came back with a vengeance.I stayed off for 2.5 months with not much improvement,then caved in...

Originally Posted by erinkj

If you have or have had anxiety then, wellbutrin is not a good med for you to be on! Wellbutrin is more deppression with fatigue type specific. It is very stimulating which is why it helps with deppression fatigue! Wellbutrin may cause an increase in anxiety and make you feel like you are shaking on the inside. It can also cause insomnia....If this were me, I would NOT take the wellbutrin or any other stimulating med.....PERIOD! Your DR. like most, is mis-informed concerning the withdrawl/discontinuation syndromes of all SSRI med's. So, I doubt this was a return of you'r original diagnosed deppression but rather a withdrawl symptom. Upon discontinuation of ANY anti-deppressant many people will experience symptoms of the original diagnosed condition which may, or may not be worse than before....That is part of withdrawl. Brain zap's are not, and never have been a symptom of deppression so, the fact that you are having the "zaps" only lends credence to the fact that it is withdrawl. How long have you been off of lexapro? and how long had you been on it? let me know...I hope you feel better soon...Peace...Erin

[Let's do something about it]

HEy all!

Thought I would write in and give an update. Over the past few months I have gone down form 20mg to 2.5. When I was at 5mg I tried going cold turkey and found out how dumb that was. So I went back on 2.5mg every other day for a week last week. So I haven't taken a pill for four days now and the only side affects that I have had were the "brain shocks" but not the "reset feeling", hot flashes-which I take care of by sitting in front of a fan, slight headaches, and a little forgetfulness and irritability. Sounds like a lot but this I can handle. And it's not on the scale it used to be. The worst was the "vertago" feeling, that's what made it unbearable. Keeping my fingers crossed hoping that never comes back. If I never experience that again then this will be a piece of cake! I do have the "Flu-like" symptoms which is to be expected but it's more like a sinus infection so its not that bad, no fevers or nausea or anything like that. It's actually been quite nice compared to two weeks ago seems like there is hope now. IF I can make it a week without Lexapro in my system and no vertago feeling the I will be convinced Im off of it and just need to bare through the slight symtpoms. The Brain shock everyone talks about feel more like parts of my head went to sleep and are waking up, its more like a tingling sensation. Really no that bad, it does happen frequently but ya kinda get used to it where it kinda tickles. I know it's weird. Anyways, I read alot of stuff on Lexapro withdrawals, I didn't really get into the whole SSRI's and why people need them like the last articles I've been reading on here but I did learn some intersting things on how to detox with less symptoms and these might help:
Aunty is right Lexapro has alot to do with hypoglausemic (for the spelling)

1. The insomnia at night comes from your body being low in sugar and the bad dreams. So here's a tip, before going to bed drink of glass of water to keep hydrated and eat a handful of walnuts, or some kinds of nuts so that your body breaks it down into sugar while you sleep.

2. During the day you might feel like you get "the shakes" or "tremors" etc. to solve this eat fruit. Obviously fruit is good sugar that your body breaks down so you don't have to worry about getting fat. But remember that it is alot of Carbs. Bananas and apples are the highest in sugar out of all the fruits so that would be a good place to start. Plus since bananas "clog" you up and apples "unclog" you it kinda works itself out into a good balance for the bowels if eating one of each a day, which in return might take care of the IBS that some are experiencing.

3. If you live near an amusement park, ride some roller coasters all day. Why you ask? don't know but I do know that I did this weekend right on the day I usually experience severe vertago, and seems like all the different states of change in eqalibrium-s.p? helped by being tossed all over the place and didn't even have to think about the vertago "dizziness" affect at all.

If these tricks help anyone besides me please respond because maybe we can help other get through the nightmares of coming off this terrible drug!