Is there any possible side effects that should be watched for , that could be life threatening - That wouldn't be obvious to someone on the drugs?
The patient wouldn't be using them at the same time, but would be daytime use of etizolam and night use of zolpidem.
Also, it should be noted that etizolam was chosen over other common benzos due to the possibility of target receptors being over stimulated 24/7 Which could lead to more severe withdrawal than normal ( the withdrawals do kill - so it was something discussed by the doc and myself).

Agreed^, GABAa agonists (or rather, strictly speaking, positive allosteric modulators) are completely unsuitable for daily use as either anxiolytics or sleep aids, unless for very short periods, short courses of a benzo, Z-drug or other GABAergic sedative, ranging from a few days to a week can be indispensable for those times when one just cannot seem to sleep, or is only getting a minimal amount of crappy, restless sleep.

Likewise for anxiety, they are perfect for dealing with a situation that would otherwise make one anxious and stressed out, such as say, for those who have a public speaking engagement and who don't do well with that, but daily use or regular use will lead to withdrawals.

GABA agonist withdrawals are  seriously nasty, much more so than even strong opioids. The potential for seizures is real, as is the possibility of fatality, it would take a serious habit though to risk actually dying.

A particular side effect of etizolam is blepharospasm, and/or twitching of the eyelids rather than full blown spasm, forcing the eye closed. It also raises prolactin levels, although I don't know if this effect is clinically significant, even if it is, I doubt its of any serious acute danger, despite the vast number of biological processes regulated by prolactin. Significant degrees of hyperprolactinaemia cause breast enlargement and milk production/release in both males and females, along with possible erectile dysfunction in males and suppression of ovulation in females. Prolactin also has immunomodulatory effects and is a ligand for several cytokine receptors.

Neuro Endocrinol Lett. 2000;21(6):475-476.
Short Communication: Prolactogenic effects of etizolam
PMID: 11335869  (no abstract on pubmed, and I have no access, ask in the ref request thread)


Journal article, fulltext on etizolam induced blepharospasm: hxxp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738986/pdf/v075p00506a.pdf

According to the article, there is a larger statistical risk the longer one is on etizolam. The duration of treatment seems far more important than the dose taken, also, there appears to be a greater risk if one is female. Most cases resolved after discontinuation of treatment, although some users (5) affected required treatment with botulinum toxin also.

Some cases did not improve though, of those patients in the study who stopped taking the drug, rather than lowering dosage, or changing drug, two of them did not improve. One was taking 0.5mg/d for 17 months, and the other took the same dosage for a period of 7 years, both without any resolution of symptoms in the follow up period of six months after the study.

Whilst duration of treatment seems an important factor, there are multiple patients in the study who developed blepharospasm after taking etizolam for a short time only, 1 month, 2 months, 10 months, some of whom required botulinum toxin treatment to paralyze the muscles responsible for the eyelids erratic, dystonic movement and blepharospasm.

Also, according to this journal article (abstract, I don't have access to the full text, but others here might) hxxp://www.ncbi.nlm.nih.gov/pubmed/11952667  longterm use of etizolam can cause a kind of skin lesions called  erythema annulare centrifugum, namely ring-shaped lesions that spread outwards, which should resolve with discontinuation of the drug, although disappearance of the lesions may take several months.

Being a thienodiazepine, as opposed to a classic, bog-standard 1,4-benzodiazepine, and bearing, to a degree, some chemical similarity with another thienodiazepine of an altogether vile nature, the antipsychotic dopamine antagonist olanzapine. Dystonias as very well known to be side effects of neuroleptics thanks to them not being selective for the dopaminergic circuits believed to be of import to the aetiology of psychosis, and affecting the nigro-striatal tract involved in movement.

Given the reports of increase in prolactin, and that certain degree of similarity of etizolam to olanzapine, I think it likely that etizolam possesses some activity as a D2 antagonist in addition to its well known GABAergic effects.

hxxp://www.ncbi.nlm.nih.gov/pubmed/12424963  This is more worrisome. It describes a case of neuroleptic malignant syndrome after discontinuing etizolam. NMS is an infrequent side effect of antipsychotics, and manifests as a high fever, disturbances in consciousness, fluctuating BP, caused by dysfunction of the autonomic nervous system, delirium, severe muscular rigidity and/or tremors, possible coma and death. NMS isn't common, but it can prove fatal.

Etizolam is apparently also an antagonist of platelet activating factor, a substance mediating various white blood cell functions, inflammation and aggregation of platelets in the blood. Makes me think it probably has some antiinflammatory properties, and may possibly prolong bleeding time in case of injury.

hxxp://www.ncbi.nlm.nih.gov/pubmed/2890779 (free full text, study focusing on the effects on platelet aggregation and etizolams effect on the platelet aggregating factor receptor)

Study gives an IC:50 of 3.8uMol for PAF-induced aggregation of platelets (rabbit) in vitro.

Looking at various studies on etizolam, it seems like it has quite a surprisingly complex and varied range of biological activity.
hxxp://www.ncbi.nlm.nih.gov/pubmed/16107249
Eur J Pharmacol. 2005 Sep 5;519(1-2):31-42.
Low tolerance and dependence liabilities of etizolam: molecular, functional, and pharmacological correlates. (abstract)
PMID: 16107249

The abstract mentions that etizolam has somewhat of a reduced tendency to induce tolerance and dependency than other benzos. Don't let that make you careless or complacent with the stuff though, or you will pay for it dearly.


As for side effects of zolpidem...heh, that one is one seriously WEIRD sedative. It can in many patients, cause a dissociated, hallucinatory experience, with little to no memory of doing whatever might have been done under the influence. People have been known to cause car accidents when they drove their car essentially on autopilot, and do all sorts of illogical, fucked up and far out things on zolpidem, this is not uncommon even at the basic starting dose of one 10mg pill, plenty of bluelight threads on the stuff, it has quite a bit of popularity as a recreational substance causing an atypical form of psychedelic experience. Highly amnestic due to its strong tendency to bind to alpha5 subunit containing benzodiazepine-sensitive populations of the GABAa receptor.

I've was scripted it for a short time in the past when I went to see my GP for some help getting to sleep, got given a Rx for zolpidem@10mg at night. Took on and reacted that way, although I remember nothing at all of the perceptual effects after it kicked in. Gave me a hell of an appetite too.

As needed use with any of this sort of drug is the safest way to use them, bloody useful at times, I always make sure to keep a couple of boxes of nitrazepam, loprazolam and a bottle of chlormethiazole caps around in case I need them.

Regular use is another matter, unless its for something like seizure control where continuous dosing to treat a permanent condition is unavoidable, I don't take my downer scripts anything like as often as my script allows for, but in the past, when I was much less experienced with benzos, and less aware of their dependence liability took a script I had at the time for 1mg lorazepam daily, for several months, and after a time, decided I no longer needed it, knew to taper but did it too fast. Ended up with severe chest pains, tachycardia, muscle spasms which ended up with my tearing a muscle in the wall of my chest, etc.  Ended up in hospital over that one, turned up to casualty, explained the situation, only for them to leave me waiting about 8 hours, and then fuck up completely by sending me home with a script for 10mg co-dydramol tablets (which are OTC here). Had a temporal lobe seizure the morning afterwards.

Also-The risk for dependence is going to be far greater when under the influence of one or the other drugs 24/7 (and don't forget the active metabolites of etizolam which have half lives similar to the parent drug)

I wouldn't say don't take benzos, Z-drugs etc. But you are going to have to be very careful, and the pattern of use you suggest is not a safe one, unless for very limited periods. Oh...and I recommend never using them for a period of time without having enough further supply appropriate to however long you used for to use for tapering, and make it a generous further supply, so as to avoid being cut off suddenly.

If 5 days a week use was going to be typical pattern -Then Would it be better to switch between drugs on regular basis?

in a nutshell, No.....the key word here being "regular"

Sadly, too many doctors are unaware of the dangers associated with modified diazepines, and the drug companies work VERY hard at keeping it this way

that said, some countries (UK, Oz) have "educated" medicos, far more than the US, as well as not having DTK (direct to consumer) advertising

Check out "paroxetine" aka Paxil and co, for a perfect example of this behaviour....there are people who have tried to taper off this drug with NO success.....aaah MILLIONS of people!!!

Also, it seems fairly clear that drugs that affect one overall seratonergic systems, have a frightening ability to cause psychotic episodes when discontinued!

Think Columbine, and most recently Norway for just a few examples

If your "stress" is mainly "physical" like exam stress or somesuch, beta blockers reduce blood presure have been known to alleviate the symptoms associated with these temporary states, as well as being effectively benign drugs overall

Beta blockers block the action of endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) in particular, on ?-adrenergic receptors, part of the sympathetic nervous system which mediates the "fight or flight" response.[7][8] There are three known types of beta receptor, designated ?1, ?2 and ?3 receptors.[9] ?1-adrenergic receptors are located mainly in the heart and in the kidneys.[8] ?2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle

  wiki..

There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known.[15] Some people have used beta blockers for performance enhancement, and especially to combat performance anxiety. In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright and tremor during public performance and especially auditions.

Matey the fact you float around here, suggests you are no fool, so be aware that doctors are no gods, and very fallible, most having little or no personal experience with the drugs they prescribe

 Bee informed, and bee careful, what you are reading here comes via LONG time experience, rather than a drug company rep

f1

Yeah I agree, I just thought throwing in some kind of alternative, may help...

personally I like diazepam, but my experience with clonazepam is "better" however I refer back to the idea that ANY mood or mind altering drugs will have some kind of withdrawals...even pot!

Stay away from venlafaxin or ANY of the SSRI family IMO they create more problems than they solve!