vekkersc, please do not get discouraged by the length of my response and choose not to read it. I believe that I can really help you and give you some really good advice. I just wanted to give you all of the information I possibly could in relation to your question; based on the limited information that was provided in your first post. I do apologize for writing such a long response and for adding a lot of extra information that you did not ask for. However, IMHO all of this information I have written so far as well as a lot more info, is very relevant when even attempting to answer the question you have asked us. I am hoping that all of this cited information is of use to you and can be somewhat helpful. I did not want to just give you a generic, short, or careless answer to a very serious and legitimate question with possible life changing consequences
First off, a little about my own benzodiazepine tolerance/dependency. I am prescribed 2mg Xanax twice a day 'as needed', and I am on long term benzodiazepine therapy. I have been on benzodiazepines for over 6 years and after having tried almost everything else (except for things that you have tried like midazolam and flunitrazepam), the Xanax was the only medication that was able to help my lower my overall anxiety, my mild insomnia, and my random panic attacks. At first I did not need it every day, nor did I usually even need the full dose. At that time (circa 2004) I was considered to have depression, general anxiety disorder, and moderate social anxiety. However, (in my experience) just by taking this type of medication every few days, or every other week (in the beginning), I still built up a tolerance rather quickly and was soon having to take the full 2mg to just to be able to leave the house. Now my diagnosis in regards to anxiety has been reevaluated to "severe panic disorder with agoraphobia and some features of psychosis".
As we start to focus on your question; when asking something like this, you have to consider all the angles and everything that can actually affect ones tolerance and likelihood to develop a physical and or psychological dependence to benzodiazepines such as, but not limited to: other GABAergic medications, supplements, vitamins, etc. For example; a type of Vitamin B3 (generally sold as some form of Niacin) is also available in the form of Niacinamide. Although is is just a vitamin "Animal studies show that nicotinamide has anti-anxiety (anxiolytic) properties. It may work in a way similar to benzodiazepines"(Tallman JF, Paul SM, Skolnick P, Gallager DW (1980). "Receptors for the age of anxiety: pharmacology of the benzodiazepines". Science 207 (4428): 274–81. ) "Niacinamide locks onto the same receptor sites in the brain as do tranquilizers such as Valium, and is a natural tranquilizer. The manufacturer of valium is also the worlds largest manufacturer of niacinamide." (Nature 278: pp.563-65,1979) This showing that even things as simple as Vitamins are speculated to help with anxiety and can influence how a specific benzodiazepine tolerance occurs and to what degree, speed, and severity.
Niacinamide might exert its effects through its modulation of neuro-transmitters that are commonly unbalanced in those areas of the brain associated with anxiety. Niacinamide might also reduce anxiety by shunting more tryptophan toward the production of serotonin and/or by simply correcting a vitamin B3 dependency Also "research indicates that niacinamide and inositol enhance the effects of GABA" (Valli M, Pringuey D. New Trends on Biochemical Mechanism of Bezzodiazepines, Therapie (sic)1980 Sep-Oct, 35(5): 561-9.). There are five sub-receptors of the sub-receptor GABA(A). These subreceptors determine the actions of a specific GABAergic drug such as benzodiazepines. For example, benzodiazepines have a high affinity for GABA(A) A1, also known as alpha-1, are highly sedating. Alpha-2 ligands are powerful anxiolytics. Each benzodiazepine has a slightly different affinity profile which makes each benzodiazepine and GABA agonist unique. However, There are many GABA agonists out there from alcohol, to Niacinamide, to benzos, to 'Z-drugs' aka "non-benzodiazepine drugs" such as Zolpidem, Eszopiclone, Zaleplon, and all those other prescription sleep aid goodies.
All of this information and more is necessary to even attempt to answer the question you have asked. A lot goes into what causes you to develop a tolerance to benzodiazepines, even simple vitamin supplements that contain Nicotinic Acid, Nicotinic Acid Amide, Inositol, etc. They can all affect your tolerance. So youve really got a lot to take into account when inquiring about how you will react to benzodiazepines, tolerance, and other GABA agonists. Also it involves your own body chemistry, your genetics, family history of addiction, whether or not you smoke tobacco. Niacinamide might exert its effects through its modulation of neuro-transmitters that are commonly unbalanced in those areas of the brain associated with anxiety. Niacinamide might also reduce anxiety by shunting more tryptophan toward the production of serotonin and/or by simply correcting a vitamin B3 deficiency. I mention neurotransmitters and tobacco only because most people do not know that tobacco smoke contains potent Monoamine Oxidase Inhibitors. "Tobacco smoke contains the [MAOIs] harman, norharman, anabasine, anatabine, and nornicotine. These compounds significantly decrease MAO activity in smokers."(Fowler JS, Volkow ND, Wang GJ, et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition". J Addict Dis 17 (1): 23–34) which affect nearly every drug, food, vitamin, whatever, that you put into your body. "Working with mainstream smoke collected from commercial cigarettes we confirmed that cigarette smoke is a potent inhibitor of human MAO-A and -B isozymes. MAO inhibition was partly reversible, competitive for MAO-A, and a mixed-type inhibition for MAO-B. Two beta-carboline alkaloids, norharman (beta-carboline) and harman (1-methyl-beta-carboline), were identified by GC-MS, quantified, and isolated from the mainstream smoke by solid phase extraction and HPLC. Kinetics analysis revealed that beta-carbolines from cigarette smoke were competitive, reversible, and potent inhibitors of MAO enzymes. Norharman was an inhibitor of MAO-A (K(i)=1.2+/-0.18muM) and MAO-B (K(i)=1.12+/-0.19muM), and harman of MAO-A (K(i)=55.54+/-5.3nM). beta-Carboline alkaloids are psychopharmacologically active compounds that may occur endogenously in human tissues, including the brain. These results suggest that beta-carboline alkaloids from cigarette smoke acting as potent reversible inhibitors of MAO enzymes may contribute to the MAO-reduced activity produced by tobacco smoke in smokers."(Herraiz T, Chaparro C. Spanish Council for Scientific Research, CSIC, Instituto de Fermentaciones Industriales, Juan de la Cierva, 3, 28006, Madrid, Spain. Biochem Biophys Res Commun. 2005 Jan 14;326(2):378-86) So back to the point
There is no real or accurate way for anyone to determine how your body will respond to the ingestion of short acting benzodiazepines and the tolerance that the use of them most likely will result in. And it is generally known that short acting benzos are more likely to cause a faster tolerance than longer acting benzos such as diazepam and clonazepam) So the only real answer I (or anyone) can truthfully give you is; no one can respond to your inquiry with one perfectly accurate or absolutely correct answer due to so many factors such as: neurotransmitters, your individual chemistry, history of addiction, family history, the fact that these meds can also make you feel good, the foods you eat, the vitamins you may or may not take, whether or not you are a smoker or spend any amount of time around smokers, the mechanism of action of benzodiazepines (even their differences between each other) and so very many other factors. So you will just have to be very careful; especially with very short acting benzodiazepines such as Halcion. So anyway you look at it, with GABAergic medications like Triazolam, you need to be even more careful than with other short acting benzodiazepines like Xanax and Ativan when it comes to developing a tolerance both physically and psychologically. Also, Nootropics can have an effect on tolerance.
Again, I am sorry this is so long, I just wanted to provide you with the most accurate and thorough answer that I possibly could; hence the citations. I see that you have tried other medications to help you with this situation. Even though I am not a doctor; however, I am majoring in premedical sciences at one of the top three research universities in the United States: I would suggest that before resorting to such short acting benzodiazapines such as Triazolam and Midazolam that you try other medications, supplements, or relaxation techniques. In absolutely no way am I an advocator for herbal supplements, but you may want to try some.
Before I could even begin to suggest alternative medications, supplements, vitamins, techniques, or any sort of more specific helpful answer, I would have to know a little more about you as well as your medical history such as; what other medications/supplements you are currently taking (both OTC and prescription), what kind of testing you have had done, what type of doctor is prescribing this to you, what, if any, other psychological conditions you may suffer from, aside from severe insomnia and moderate social anxiety, as you mentioned in your post, as well as some other things.
Out of my own curiosity, what have you tried prior to Flunitrazepam? Even though it is a schedule IV medication like other benzodiazepines and it is an intermediate acting benzodiazepine derivative with very very potent hypnotic and sedative effects; because of its current reputation, I am wondering if you been hospitalized due to your severe insomnia or your anxiety problems to obtain prescription for Rohypnol in the first place. I only ask that because this particular medication is usually reserved for severe insomnia for people in inpatient hospital care and is not generally a prescription given often outside of a hospital. Other sleep aides such as Doxylamine, Benadryl, Z-drugs (though cross tolerant with benzodiazepines), and others are generally more common, safer, and usually better for the patient before doctors resort to benzodiazepines for sleeping issues (even though they seemingly work well for sleep related issues). This is because when benzodiazepines are used for the treatment of sleep issues such as insomnia, they disrupt the natural sleep cycles of the mind and decrease delta wave activity in the brain during benzodiazepine induced sleep. For now, there is not definitive reason for this because the effects of benzodiazepines (like Flunitrazepam, Midazolam, Triazolam, etc) on delta waves may not even be affected by the actual benzodiazepine receptors. In case you were not aware, delta wave activity is an indicator of the depth of sleep within non-REM sleep and the higher the levels of delta wave activity during sleep indicates a better quality of sleep. This means that Flunitrazepam as well as other benzodiazepines, usually cause an overall deterioration in sleep quality because of the decreased delta wave activity. The fact that benzodiazepines contribute to a lower quality of sleep could be contributing to your severe insomnia and anxiety issues and possibly creating a cycle making your conditions progressively worse. Something that I have recently learned about is that there have been new studies and evidence supporting the fact that Periactin, and antihistamine, can in fact help people who suffer from severe chronic insomnia. I honesly know very very little about this medication except for the fact that it is used generally used to help people who are suffering from mild or moderate cases of serotonin syndrome and has been shown to relieve nightmares related to PTSD. It does have adverse effects on growth hormone by suppressing it when Periactin (Cyproheptadine) has been used in doses of higher than 8mg a day for more than 5 days in a row. Even with the anti serotonin effects on the body that this medication has, it has recently been shown that "Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia as it enhances sleep quality based on EEG studies.", (Tokunaga S; Takeda Y, Shinomiya K, Hirase M, Kamei C (February 2007). "Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats" (pdf). Journal of Pharmacological Sciences 103 (2): 201–6.) Though as far as the use of antihistamines for sleep, I would definitely try something that does not appear to affect serotonin so much since serotonin as well as other neurotransmitters play a crucial role in so many aspects of your overall health. Also Cyproheptadine may actually cause sleep problems and depression because of its anti-serotonin effects because a hormone that promotes sleep is directly related to and comes from serotonin called (N-acetyl-5-methoxytryptamine) more commonly known as Melatonin. Though most people do not know that melatonin is directly related to serotonin; actually requiring serotonin to be synthesized naturally in the human brain for our body's natural sleep rhythm. It begins with Tryptophan (which is what makes you tired after you eat turkey) which is catalyzed by the enzyme tryptophan hydroxylase into 5-Hydroxytryptophan (5-HTP) which is decarboxylated to form (5-HT), which is in fact Serotonin intself; which we know cannot cross the BBB. Therefore there is currently much debate and many studies being done testing the the effects of extended use of Cyproheptadine and how it could in fact cause a lot more problems than benzodiazepines thereby negating the entire argument of cyproheptadine's supposed superiority to benzodiazepines for insomnia issues.
That is one of the reasons that benzodiazepines are generally indicated only for short term (generally 4-6 weeks as needed) relief of anxiety, panic, insomnia, etc; because in the long run, long term use of benzodiazepines usually exacerbates the original problem that required the medication in the first place. This is why I mentioned my own experience with my current Xanax issue in the beginning of my response (how I went from a vague diagnosis of generalized anxiety disorder/social anxiety to the severe panic disorder I suffer from now and the increase in frequency and the severity of my panic attacks). Now I am physically dependent on benzodiazepines and I do go into withdrawal if I do not have some sort of benzodiazepine type medication daily, I experience withdrawal and risk seizures and all the other fun stuff associated with benzodiazepine withdrawal. The absolute best thing you could do when it comes to benzodiazepines is do your absolute best to avoid them, or take as low a dose as possible for as little time as possible, then gradually change to a different type of sedating medication like benadryl, doxylamine, Hydroxyzine, as well as other antihistamines. And of course, there are other sleeping aids than just the ones we have discussed.
If you would like me to give you a better more concise response, you can PM me with some of the additional information I mentioned above, or you could respond in the thread, whichever you are comfortable with; if you even want to that is. I would like to try my best to answer your question, or at the very least help you with your issue of sever insomnia and moderate social anxiety before it gets worse and requires even stronger medications. I will even do some research from medical journals in my library (as well as online) and if necessary, speak with my professors if you would like. I just do not want you to end up in the benzodiazepine circular hell that I have gotten myself into. Just PM me or respond on the thread and let me know if I can do anything more to help.
