Fentanyl and anti-depressants - what works?

Under construction not complete for all revisions until this sentence is gone. I will periodically save in order to not loose info. Please, comeback and read when complete. I'm going to leave this as under construction for a few days. I find coming back and reading these things after a few days allows my brain to process it better. Thanks sas

The following is a pm between myself and another member whose name I have deleted. She asked me to look at a combination of things she put together because she had horrible insomnia. It was done in three PM's which I had her send back to me.

Her particular question was how would these OTC drugs interact with her Wellbutrin. When I looked at the OTC drugs it was in relationship to Wellbutrin. As I studied them I mentally noted how they would affect other SSRI's & SNRI's.

My cautionary to her was be cautious about suggesting this group to others b/c unless a serious look was given to what other drugs were on their list, it may be a problem. I have obviously decided to put my research her. The reason is there's allot of research, I don't want it lost. If someone were to consider taking any of these, please, use dailymed.nlm.nih.gov and Wiki to study how your drugs and these drugs work together.

As in all writings like this study them, and talk with your physician before taking and new med OTC or prescription.

I'm going to revise some.

 Remember--all drugs have consequencs.

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PM from BCO friend

"Hi SaS, Here are the 3 messages you sent, as you requested. I combined them into one.

So maybe I am pretty smart after all (HA!). I went to Costco today and found a product by Schiff Nutrition Group called "Melatonin Ultra". It has 5 mg B-6, 52 mg Calcium, 3 mg melatonin, 25 mg L-theanine, 25 mg GABA and an 8 mg proprietary blend of chamomile extract and valerian extract. So no 5-HTP but a little bit of the other things I'm taking plus the B vitamins you suggested! I'm going to look into what the calcium adds to the mix."

*member name deleted

(The following is an evaluation by sas of the drugs that the member put together for insomnia).

5-HTP  The 5HTP was recommended by her psychiatrist. I hadn't heard of it before. I was impressed with how necessary it is to making serotonin, melatonin, and tryptophan. Wiki gives a nice explanation. But this is one of the reasons that someone would not just want to take it without evaluating it against your own drugs. 5HTP is a precursor to serotonin. That means it is involved in making serotonin. If you make more serotonin, then more is available for work at the nerve ending when it's stimulated and released into the space between the nerve endings.

The body recycles serotonin by taking it back up into the nerve ending to use again when the next stimulus is received.

The SSRI's(Selective Serotonin Re-uptake Inhibitors) and SNRI's(Selective Serotonin Norepinephrine Re-uptake Inhibitors) work by inhibiting serotonin (and Norepi as in SSNRI's) from being taken back up into the nerve ending. By having more serotonin in the space between nerves it allows the stimulation of the next nerve ending on a prolonged basis.

So, theoretically, If you produce more+ inhibit reuptake does that equal more than necessary serotonin in the space.  If that were true what does that mean? I.E. could we get in trouble? Not sure I could find the answer to that one. The easiest answer is consider using 5HTP for a few weeks before considering a SSNRI or SSRI.  Reason: it's within the body and can be taken as a drug that mimics a chemical normally within the body. Versus a chemical like the SSri's/Snri's that interferes with a body process. That body process we know has to be altered slowly when discontinuing the inhibitors b/c it can cause serotonin withdrawal syndrome.

In Europe it is used in many anti depressants drugs. Not so in the USA b/c it would have to be put through clinical trials to pass FDA approval. Since it can't be patented, our drug companies aren't interested.

 I have included the Wiki link for 5HTP

I went to other evidence based web sites and they were way to difficult to decipher. Wiki I have learned over time is really a good source b/c they try to keep it simple

http://en.wikipedia.org/wiki/5-Hydroxytryptophan

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Melatonin----CYP 1A2 major and 2C19 minor. Can have a interaction with Fluvoxamine, USA FDA approved SSRI. Luvox is the trade name approved 1994. Never ever saw it till this search. Not likely you will see it either. But over many pages it kept referencing it. Then when Wiki told me it was approved in 1994 for OCD, I got it. Not that many with serious OCD, that I've had contact with.

There can be some interaction with Wellbutrin at 1A2, but nothing to get excited about i.e no red flags there.

Wellbutrin when I researched it while on Hot Flash forum, I noted I would have sworen it was an SSRI. At the time only a couple of years ago it said it was a dopaminergic--dopamine. Wiki says that's no longer true. Some more evidenced based stuff must have been published LOL. Whatever----it affects Dopamine and serotonin-----so, let's say it's a serotonergic& dopaminergic.

Cyp for Wellbutrin is 2D6-----1A2-----2B6. Can't read my own notes. At one of these sites it is a potent inhibitor. Another note I wrote down was "care should be taken when initiating or discontinuing the drug". Also, use with caution in liver/kidney/and hypertension.

Editing: This is a link to wiki about melatonin. Everything  you would want to know about it.

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

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GABA Again I used Wiki, didn't even bother with other sources.

http://en.wikipedia.org/wiki/Gamma-Aminobutyric_acid

1. GABA ingested/injected does not cross the blood brain barrier. But is converted to a chemical that can.

2.There was one study that orally administered GABA can increase Human Growth Hormone. Sleep deprivation can suppress it's production b/c it's produced during a phase of sleep. I'll link to Wiki',s Human growth Hormone page.

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

I don't see you taking GABA as a problem, as many parts of the body use it. Wiki-- "GABAergic mechanisms have been demonstrated in various peripheral tissues and organs including, but not restricted to, the intestine, stomach, pancreas, Fallopian tube, uterus, ovary, testis, kidney, urinary bladder, lung, and liver.[27]"

But I do see one cautionary. Wiki "In 2007, an excitatory GABAergic system was described in the airway epithelium. The system activates following exposure to allergens and may participate in the mechanisms of asthma.[28] GABAergic systems have also been found in the testis[29] and in the eye lens.[30]" I would suggest not to be used by asthmatics or possibly someone with cataracts(lens). No clue about the testis affect or consequence---we don't care do we?

I would suggest taking a B complex as there was mention of having B6 and Niacin in GABA's metabolism work. Not sure exactly how. But a B complex is great anyhow, so, it can't hurt. B complex is different than a stress B. Stress B has C in it. I think if you are going to take C use Hi C foods . The range of B's can be hard to get in the diet unless you work at it. . Years ago I did research it, I was convinced enough of B complexes need I take it daily. Great for anyone that drinks alcohol.

3. Useful in stress. Wiki--"While GABA may not cross the BBB(blood brain barrier), it is important to note that studies have shown that, within stressed individuals, GABA does indeed have a positive effect, albeit with side effects.[50]The only way to deliver GABA effectively is to circumvent the blood-brain barrier. Indeed, there are a small, limited number of over-the-counter supplements that are derivatives of GABA, such as phenibut and picamilon. Picamilon combines niacin and GABA and crosses the blood–brain barrier as a prodrug that later hydrolyzes into GABA and niacin.[51]" See number 1.

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Theanine Wiki. "Theanine has been reported to raise levels of brain serotonin, dopamine, and GABA, with possible improvement in to specific memory and learning tasks.^{[37][bare URL]}

The Wiki Theanine page is very technical, my head was swimming. I suggest drinking caffeinated TEA that has Theanine in it. it gives a small dose of about 20 mg per cup. it's cheaper then buying the supplement.

In theWiki page on glutamate, look at the neurotransmitter section. Besides all the other good stuff it does is it a precursor for GABA synthesis(making of) in the brain. Additional Theanine enhances the use of the GABA you are taking to help make GABA in the brain.

 Wiki http://en.wikipedia.org/wiki/Theanine

Phew---noise not a chemical abbreviation. Earlier, I said over-read the statistics in published articles and abstracts. This can be applied to some of my writing too.

Sorry if the above post seems a little hard to follow or allot. Needed to have it out there incase something happens to me.

Helloooooooooooo Lily Thanks, I have a tendancy to get into Terms Of Use trouble. If I weren't able to come back, I have too many things in storage that would be lost forever. The above post is confusing -------so much info. I decided to post it today b/c someone wanted help on their insomnia drugs. Remembered this post from a few weeks ago. So much I had already forgotten.

In a study like this I used to remember forever, NOW ------Not.     Thanks to BC etc.

To all, Wrenn deleted the above post at my request. I had my real name in the long post. She wondered who _______was, It was OOPs Wrenn can you delete that     I have no problem with anyone on BCO knowing my name, but not the outer world.

Fentanyl.(repost from another thread I was working on)

I'm including the black box warning in it's entirety. Not sure as yet, how I will annotate it. But will reinforce the last paragraph regarding heat sources since you will be using the heating pads. The statement at the very end is very well written. If you start using Fentanyl, you would have to discontinue the total body warm moist heat. But if the trade off is better pain control, it doesn't matter how you get there as long as you get there.

Not sure what your MO knows about the drug, if he thinks it only works for a small area. All Opiods work by affecting the opiod receptors in the brain which positively affects the whole body. Plus, Fentanyl has a positive serotonergic affect. That means it mimics the positive affect of increasing serotonin availibility( mechanism I'm not sure of). The antidepressants SSRI's & SSNRI's(see fentanyl thread for list if questions) increase serotonin. Fentanyl is the only opiod that has a positive serotonergic affect. It's two for one drug.

What's different about fentanyl from the other opiods is it doesn't space you out unless the dose is too high. My pain was the entire musculoskeletal system. Post polio & fibromyalgia  induced by the Aromatase inhibitors. The day I started, I was a pain scale of 10. Like you the tears were flowing. I was WORN out by pain. It was heaven as the drug started to take effect.+- 18 hours. The pain melted away. Memory on pain scale with it on, is sketchy. I was so used to living my life with a 5-7(predominantly 5). For the duration that I was on Fentanyl, pain control was effective enough that I rarely took meds for breakthrough. I had an OXY script of 120 pills prescribed to be taken every 4-6 hours for breakthrough. If you calculate that out, it was enough for a month. That script lasted 18 months versus 1 month.

The lovely positive serontonergic effect was one of mellow well being for the duration. Not High. Not spacey. With Oxy 10 mg,  I'm spacey without great pain control and a bit spacey on 5 mg. I much preferred Fentanyl over Oxy.

In the Duragesic monograph below you will see the discussion regarding 3A4. All opiods go through 3A4. My 3A4 is a intermediate metabolizer which means I process it slowly. At the time I was using it, we didn't know that. You've read the "Panicking about Pain" thread. I developed a 7 day plan. I won't restate it here. What it means for you is that you should have your genetics done. I'm taking an educated guess here that you are a rapid metabolizer at 3A4, b/c you are taking high dose without relief but are symptomatic with negative s.e.'s. Doesn't matter if I'm wrong or right. Testing of your 3A4 is critical to your pain control. Depending if there is an aberration in the metabolism, dosing of anything going through 3A4 should be adjusted. Likely hood if I hadn't developed my 7 day plan, I would have been overdosed if I had changed the patch every 3 days

With Genelex testing for the panel is as cheap as testing for one.(see Fentanyl thread). For completeness her the panel includes 2D6, 2C9, 2C19, 3A4, 3A5, Vkroc1.

Dosing: Ask for the 25 mcg patch to start.. They come in a box of 5. If after one week of use pain is not in target range and s.e's none to minimal discuss using 50 mcg. But as you go up in dose s.e's will become more prominent as is the case with all drugs. Once they screwed up my script and gave me 50 mcg. I used them , but was spacey.

Skin prep: Wash application site with non oily soap and dry well. Patch will fall off if the skin is oily. Avoid cleaning skin with alcohol before application. Might set you up for skin irritation. Application site should be moved around to avoid skin from becoming irritated from the adhesive. If a patch comes off, it's designed to not be able to be reapplied.

Skin site selection: Most practioners recommend the upper back area. I recommend anterior upper chest. Reason is if you become unconscious for any reason the upper chest area is exposed by EMT's/doc's to evaluate breathing. In an unconscious state the patch would be identified and removed. If the patch is on the back it may be missed.  Long term use, consider a Medic Alert bracelet.

Initiating drug: Ask for a HomeHealth Referral for "Evaluation of Medication" change. There's an ICDM-9 code for it that the HHA will use. It's covered by insurance. The importance of this is that the nurse will evaluate how you are responding to the drug. It's necessary to be done in your surroundings versus going to the docs office. This evaluation is usually done over 1-2 weeks. Should be repeated if there is a dosage change. review the monograph to educate yourself about the drugs workings.

Storage and disposal: Keep in a secure area from children and pets. Dispose of in the trash that is then secured. Disposal is controversial as it is with all drugs now. Drugs used to be recommended to be put done the toilet. Drugs were affecting the environment. In the trash it goes to the landfill. Communities have developed drug disposal plans.

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Drug Monograph 

Black box warning for Fentanyl( black box warnings means that these are serious considerations regarding a drug).

DURAGESIC^® (fentanyl transdermal system) CII contains a high concentration of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances which include fentanyl, hydromorphone, methadone, morphine, oxycodone, and oxymorphone have the highest potential for abuse and associated risk of fatal overdose due to respiratory depression. Fentanyl can be abused and is subject to criminal diversion. The high content of fentanyl in the patches (DURAGESIC^®) may be a particular target for abuse and diversion.

DURAGESIC^® is indicated for management of persistent, moderate to severe chronic pain that:

• Requires continuous, around-the-clock opioid administration for an extended period of time, and
• Cannot be managed by other means such as nonsteroidal analgesics, opioid combination products, or immediate-release opioids

DURAGESIC^® should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to DURAGESIC^® 25 mcg/hr. Patients who are considered opioid-tolerant are those who have been taking, for a week or longer, at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid.

Because serious or life-threatening hypoventilation could occur, DURAGESIC^®is contraindicated:

• In patients who are not opioid-tolerant
• In the management of acute pain or in patients who require opioid analgesia for a short period of time
• In the management of post-operative pain, including use after out-patient or day surgeries (e.g., tonsillectomies)
•   In the management of mild pain
• In the management of intermittent pain (e.g., use on an as needed basis [prn])

(See CONTRAINDICATIONS section of the full Prescribing Information for further information.)

Since the peak fentanyl concentrations generally occur between 20 and 72 hours of treatment, prescribers should be aware that serious or life-threatening hypoventilation may occur, even in opioid-tolerant patients, during the initial application period.

The concomitant use of DURAGESIC^®with all cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Patients receiving DURAGESIC^®and any CYP3A4 inhibitors should be carefully monitored for an extended period of time and dosage adjustments should be made if warranted. (See CLINICAL PHARMACOLOGY-Drug Interactions, WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections of the full Prescribing Information for further information.)

The safety of DURAGESIC^®has not been established in children under 2 years of age. DURAGESIC^®should be administered to children only if they are opioid-tolerant and 2 years of age or older. (See PRECAUTIONS - Pediatric Use section of the full Prescribing Information.)

DURAGESIC^® is ONLY for use in patients who are already tolerant to opioid therapy of comparable potency. Use in non-opioid tolerant patients may lead to fatal respiratory depression. Overestimating the DURAGESIC^® dose when converting patients from another opioid medication can result in fatal overdose with the first dose (see DOSAGE and ADMINISTRATION – Initial DURAGESIC^® Dose Selection - section of full Prescribing Information for further information). Due to the mean elimination half-life of approximately 20-27 hours, patients who are thought to have had a serious adverse event, including overdose, will require monitoring and treatment for at least 24 hours.

DURAGESIC^® can be abused in a manner similar to other opioid agonists, legal or illicit. This risk should be considered when administering, prescribing, or dispensing DURAGESIC^® in situations where the healthcare professional is concerned about increased risk of misuse, abuse, or diversion.

Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse, or addiction.

DURAGESIC^® patches are intended for transdermal use (on intact skin) only. Do not use a DURAGESIC^® patch if the seal is broken or the patch is cut, damaged, or changed in any way.

Avoid exposing the DURAGESIC^® application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs and heated water beds, while wearing the system. Avoid taking hot baths or sunbathing. There is a potential for temperature-dependant increases in fentanyl released from the system resulting in possible overdose and death. Patients wearing DURAGESIC^® systems who develop fever or increased core body temperature due to strenuous exertion should be monitored for opioid side effects and the DURAGESIC^® dose should be adjusted if necessary.

Wow! Schatzi you are da bomb! How very compassionate and generous and knowledgable! You rock. Thanks for sharing.

Aio. Hope this helps. I know you eat well and walk daily. I have found fish oil and a light therapy box help my mood. I found the box on amazon.

I think you have been dealt a terrible hand. You are still processing and unfortunately the crap never ends. Out if the blue you lost your job/identity and your health. Now you've lost your home and contemplating your possessions. Fair play that you want a better mood and not wallow in your misery.

I take Xanax at night to help sleep. I have split the dose in half if I feel I need it during the day. I am looking for a cognitive behavioral therapist to help redirect my thinking. Regular talk therapy makes me feel better for a little while but I climb back in that stupid hamster wheel and my thoughts go round and round. Journaling also helps for the moment. I'm still trying to find a hobby I'm passionate about.

Do you think you could do tai chi?

Just know there is someone always here if you need to vent/rave. No one really understands except those that are walking the same path.

Bach's remedy ---the candy?  Give..... We need what ever works sassy

Can you copy more info and I'll try to research it .Thanks Zill, sassy

Z are they still using brandy as the base for the Bach? I used to use it for my dog. Good stuff

Zil  I can't offer insight into Bach's remedies. Research on these types of things doesn't happen b/c the big pharma companies can't patent them. Without well controlled studies it's an unknown as to how they work, interact, etc.

I was going to write that all medications come from four sources. Typical, I couldn't remember all. Googled it. There are two more sources from the time, I used to have to teach it. It was a duh moment as we read about 5&6 lots in relationship to BC and other conditions and they have been around awhile.

Drugs are obtained from six major sources:

1. Plant sources
2. Animal sources
3. Mineral/ Earth sources
4. Microbiological sources
5. Semi synthetic sources/ Synthetic sources
6. Recombinant DNA technology

I have teas that contain many of the same things Bach's uses, so, even though I can't say something, I do use some.

Not sure what that number 7 is doing hanging out there, but it doesn't show on my page writing this     ?

Bump

Whoa Nellie-------------Aio LOL, I posted this a couple three or four years ago on Insomniacs thread in the topic box. I have never looked at it again.

"May help with sleeplessness: circadian rhythm, melatonin--pub med evidence based research. http://www.ncbi.nlm.nih.gov/pubmed/21476953   Agometaline is approved for use in Europe/Australia  for insomnia. It is NOT approved in the USA   http://en.wikipedia.org/wiki/Agomelatine "

When I put the 'valdoxan, melitor or thymanax' in google it brought up Agometaline. The drugs appear to be available still only outside the USA as they are not in the dailymed.nlm.nih.org data base of drugs.

Can't remember if I've said it here Wikipedia is a good source of info. It defines. Then goes through sections explaining. It brings together the history of whatever the topic is decently. From reading this again from long ago. This topic in Wiki has immensely expanded. Which is typical to Wiki b/c it's designed to be added too. I learned that Novartis bought the rights to work through approval process in USA. In 2011 it dropped Agometaline after a clinical trial. The bibliography link required a registration. No point b/c this 2015. Dead issue in USA. But it's gotten to Ireland AIO.

Look at how it's metabolized-----compare it to what I previously wrote. It doesn't go through 2d6 or 3a4. It doesn't say it, but it's primary route is 1A2. It mentions others.

A section I particularly liked was the way Wiki presented the side effects.

Sometimes Wiki can make me/you crazy with all the hyperlinks. But it's good if you chose to read further. Those links come from all the folks adding things to the topic trying to expand the knowledge about the topic.

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

I love research . It's all the new stuff that I learn. AND the things I bump into along the way. The research around Melatonergic  activity was kind of dead ended when I looked at agomelatonin a few years ago. But it was ALIVE and being researched. This article was dated Feb 2015. talks of melatoninergic  potential of helping neuropathic pain. This is huge for our BC community. Novartis dropped the ball, the folks in Novartis's boardroom are probably not happy. Still haven't found out what happened with Novartis. May sound like a 'who cares?' All kind of questions?

 BTW When you check this link out, put the home page in your favorites. It's search mechanism is internal to the web site. The articles authors have done the literature research and done an interpretation. It's then written in almost humanspeak versus sciencespeak.

LOL anyone that has followed my writings , knows I'm prone to making up words.

http://www.news-medical.net/news/20150219/International-study-shows-potential-new-therapy-to-treat-patients-with-neuropathic-pain.aspx

International study shows potential new therapy to treat patients with neuropathic pain