Some older knowledge may give some hints - and moreover: should (at least) not be forgotten :-)

1: Rush CR, Frey JM, Griffiths RR. Zaleplon and triazolam in humans: acute

behavioral effects and abuse potential. Psychopharmacology (Berl). 1999

Jul;145(1):39-51.

2: Piper A Jr. Addiction to benzodiazepines--how common? Arch Fam Med. 1995

Nov;4(11):964-70. Review.

3: Byrne A. Benzodiazepines: the end of a dream. Aust Fam Physician. 1994

Aug;23(8):1584-5.

4: Warneke LB. Benzodiazepines: abuse and new use. Can J Psychiatry. 1991

Apr;36(3):194-205. Review.

5: Juergens S. Alprazolam and diazepam: addiction potential. J Subst Abuse Treat.

1991;8(1-2):43-51. Review.

6: Smith DE. Benzodiazepine dependence potential: current studies and trends. J

Subst Abuse Treat. 1984;1(3):163-7.

Michael,

If you had to summarize the finding of these research articles, how would you do so?

Addiction and dependency are more complex phenomena than can be explained by looking simply at the pharmacology. Many substances and behaviours create dependency without any biochemical mechanism and some people are more prone to developing addictions than others. The half life of the drug may be one feature in abuse but abuse comes before addiction, use before dependency. I wonder if individual metabolism of psychoactive drugs by P450 cytochromes may be a potent factor in addiction as well as psychosocial pressures.

Most benzodiazepines can cause some physiological dependence. However the ones which have short half life tends to cause more dependence.

Several factors come into play: Dosage, duration, potency, half-life, individual susceptibility to addiction, individual differences in how the drug is metabolized, and more. Most docs avoid short-acting alprazolam, for example, because some patients "feel" the withdrawal as the dose wears off, then desire more drug to avoid this dysphoric state. Each person is different. There is a clinical summary here: http://www.aafp.org/afp/2000/0401/p2121.html. It is outdated but is freely available and will give you some clinical questions to consider and some reference leads.

Medications like alprazolam and valium seems to have more abuse potential.

BZD with a short half-life have a higher potential of abuse.

Fulltext available.This should be useful. The paper does not hald a unitary answer.

And probably the risk of these outcomes is different with different individuals; at least it appears to the clinician that no-one is immune but people bear different risks for different substances.

Pharmacol Biochem Behav. 2008 Jul;90(1):74-89. doi: 10.1016/j.pbb.2008.01.001.

Epub 2008 Jan 12.

Abuse and dependence liability of benzodiazepine-type drugs: GABA(A) receptor

modulation and beyond.

Licata SC(1), Rowlett JK.

Over the past several decades, benzodiazepines and the newer non-benzodiazepines

have become the anxiolytic/hypnotics of choice over the more readily abused

barbiturates. While all drugs from this class act at the GABA(A) receptor,

benzodiazepine-type drugs offer the clear advantage of being safer and better

tolerated. However, there is still potential for these drugs to be abused, and

significant evidence exists to suggest that this is a growing problem. This

review examines the behavioral determinants of the abuse and dependence liability

of benzodiazepine-type drugs. Moreover, the pharmacological and putative

biochemical basis of the abuse-related behavior is discussed.

PMCID: PMC2453238

PMID: 18295321 [PubMed - indexed for MEDLINE]

My answer - multifactorial, specifying for discussion the definitions of addiction, dependence to be used w/ some precision is a good idea. I'm tending to think of dependence as connected w/ manifesting pharmacologic tolerance and a withdrawal syndrome (and the latter may include features that can be directly measured and features which have to be reported by subjective account, or interpreatation of behavior - so this can confuse the issue right away.) While I'm thinking of addiction as a syndrome of drug-seeking, compulsive drug administration, self-administration despite consequences, and usually the facilitated return or reinstatement of self-administration, which often reaches previously achieved doses involving tolerance. As well as tolerance/withdrawal,what we call reinforcement probably must be involved in addiction defined this way. Prazosin and propranolol will manifest purely pharmacologic tolerancnd withdrawal, but no-one I'm aware of has broken into a pharmacy to steal those medications. Reinforcement to me appears to be related to factors involved in substance speed of entry to the brain and duration of effect (half-life probably part of that). Crack cocaine> IV cocaine> snorted powder cocaine> chewed cocaine leaf w/ a little alkali on the side to promote liberation of the alkaloid into solution. Speed of entry varies w/ each method of administration.

A model for drug seeking that likely corresponds to motivational aspects of reinforcement would be conditioned place preference. A model for subjective reinforcing effects would be drug discrimination trials, these are usually comparative with substances that we commonly accept as producing the addictive syndrome reliably. As a patient once said to me, "The xanax really comes in handy when I can't get what I'm looking for right away." Substitute medication of choice, of course.

Hope that's helpful.

Rob

Long acting benzos are slightly better.

Hello,

i just wouldnt be me if I didn’t challenge posts made against benzodiazepines (BZDs). First, let’s start with some common ground, BZDs ARE prone to causing dependence in those who use them for long periods of time. BUT! Guess what, all SSRIs/SNRIs, TCIs, irreversible MAOIs, pregabalin and many others cause the same frustrations (Nielsen et al., 2011; Pande et al., 2003).

What’s more is that, before the gigantic pharmaceutical push for antidepressants, and the accompanying slick change in the definition of addiction and dependence in the DSM-3 to demonize BZDs (Nielsen et al., 2011; Starcevic, 2011), there was and still is an abundance of research showing just the opposite. for example, one study showed that in patients taking diazepam in dosages up to 60mg/day for numerous years had minimal to no withdrawal (Bowden et al, 1980). of note, is that, situations Where BZDs are associated with addiction they are seldom to never the sole drug of use (think ethanol, opioids, and as a comedown agent for stimulants).

Allow me to further elaborate on this statement with a cogent deduction; addiction studies in animals are useful, but they do not fully represent the complexity of human drug consumption In its entirety. Therefore, the addictive potential tends to be more severe in animals (think cocaine using rats that were caged with nothing else to do but use blow till they died) than humans. Now, what if there were multiple animal studies failing to show a reinforcing effect of BZDs (more specifically chlordiazepoxide, diazepam and triazolam) (Woods et al., 1992). Is there a paradoxical addiction occurring In humans but not rabbits, rats, and primates? Of course not, the studies were augmented with drug regimens of ethanol and other proven reinforcing drugs to create a conditioned response associated with the BZDs. Once a plethora of substances were given, the animals sometimes found reinforcement from BZDs (Woods et al., 1992).

I don’t need to ramble for too long, and I am writing this response on my iPad which is hellish and probably jam packed with typos. But I Will say this, the attachment is a figure showing the likelihood of abuse of various sedative and as you can see, quazepam is less likely to be abused than benedryl Whereas the other traditional sedatives are ranked as would be expected (Griffiths et al., 2005). I say this final part in order to address the initial question that NO not all BZDs are the same in terms of addictio/dependence.

sorry, one more note. Robert Coberly’s response was great In terms of differentiating dependence from addiction. However, the asshole in me coupled with my OCD is unable to dismiss the reinforcing order of Cocaine; it’s intravenous > smoking = rectal > insufflation > oral with corresponding rates of absorption being 100%, 80%, 80%, 60%, ~=40%. Sorry for nitpicking and being annoying, but let’s avoid demonizing crack because we are 30 years over an epidemic used to demonize Black Americans.

Sincerely,

Logan Netzer

References:

Bowden C, Fisher JG. Safety and efficacy of long term diazepam therapy. Southern Medical Journal. 1980;73(12):1581-4.

Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: A conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry. 2005;66(suppl 9):31-41.

NielsenM, Hansen EH, Gøtzsche PC What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitor. Addiction. 2011;107:900-8. doi: 10.1111/j.1360-0443.2011.03686.x

Pande AC, Crockett JG, Feltner DE, et al. Pregabalin in generalized anxiety disorde: A placebo-controlled trial. Am J Psychiatry. 2003;160:533-40.

Starcevic V. Have anxiety disorders been disowned by psychiatrists? Australasian Psychiatry. 2011;19(1):12-6.

Woods JH, Katz JL, Winger G. Benzodiazepines: use, abuse, and consequences. Pharmacological Reviews. 1992;44(2):151-347.

I have found that the addictive potential of some, such as Alprax, is more than others. Probably related to potency and half-life.

In general, anything that works quickly to produce relief of pain or anxiety or that quickly produces a feeling of euphoria is addictive. Slow is best in many areas of life.