It sounds a little bit  like the first experiences made with the Z-drugs... we see a big potential of missuse and a fast loss of effect in IVDUs. The street price is high for pregabaline - so I think, we shout be very careful wirh this drug!

I took pregabalin (75mg) for around 9 months last year as a treatment for trigeminal neuralgia (didn't completely eradicate the pain but did make it manageable).  One thing I noticed from day 1 is that my tolerance for a whole range of substances changed - for me, most noticeable was caffeine where I could suddenly drink at least twice the amount of coffee without any of the nasty side effects (e.g. nausea, agitation, tremors).  I also found I was enjoying the caffeine more and because I could drink more, I wanted more.  My tolerance/desire for nicoteine also increased as did my tolerance (although not desire) for alcohol.  I also found pregabalin interfered with my sleep patterns - most noticeably dreaming (I've always been a vivid dreamer so felt kinda ripped off when I no longer had, or could not remember, them).  On the +ve side, when I stopped the pregabalin, everything went back to the way it was before within a matter of a few days.  Based on my experience, I would be somewhat dubious about using the drug in addiction treatment...yes, it stopped the "buzz" of alcohol for me, but I drink for taste not effect so I actually found the pregabalin useful - instead of politely excusing myself at social events after 2 or 3 drinks (so I could go to bed!), I could easily manage much more.  And it's effect on me with caffeine was, perhaps, concerning - not only could I drink more coffee, I was enjoying it more and wanting it more...for an addict struggling with "wanting" a substance, I'm not convinced that's an ideal outcome.  As with other addiction drugs (e.g. Champix) there is probably a huge amount of individual variation...and pregabalin is likely extremely useful for some people with addiction issues...but as a general purpose treatment, I'd like to see a heck of a lot more research conducted first - I suspect its efficacy would be somewhat limited outside of epilepsy and neuralgia treatment.

Bernadine,

It's not surprising that pregabalin, a neuroleptic and gabaergic drug, would reduce the "side effects" of stimulants like nicotine and caffeine.  Theoretically, it would *increase* the effects of alcohol - so your experience is very interesting (and anomalous from some research reports).  

In the US, pregabalin is prescribed widely for psychiatric uses - predominantly to treat mood lability and also anxiety.  It's usefulness in (a) detoxification and (b) substitution for alcohol/opioid/benzodiazepine dependence has not yet been sufficiently studied, but it is used in clinical practice for those purposes -- from the clinicians I've spoken with, it's viewed as safer than benzodiazepines.  However, some disagree.  

Neurologically, it's an interesting drug, because it seems to upregulate glutamate as well as GABA - which is where it differs from most benzos and other neuroleptics.  

Best regards,

Devin

Chaim,

With regard to abuse potential of pregabalin, I think your fears may be justified, but there is also considerable evidence to the contrary.  In the US, the FDA & DEA (Drug Enforcement Agency) classifies pregabalin as a Schedule 5 controlled substance, which  means it has the least abuse potential of any controlled substance.  For example, oxycodone and other drugs with opioid-binding potential like heroin are Schedule 2 (most dangerous in terms of addictive potential), hydrocodone and buprenorphine are Schedule 3, benzodiazepines are in Schedule 4, and Schedule 5 is the province of drugs determined to be relatively safe.  I'm not saying the US regulatory authorities are the final word here, but they generally are close to right.  

In terms of rapid development of tolerance, I have seen studies showing that pregabalin has a much steeper dose-response curve and slower tolerance development than BZDs.  In fact, it seems to be common practice to use pregabalin to detox patients taking large doses of benzodiazepines.  

Anecdotally, at least here in the US, there is little to no abuse of pregabalin of which I am aware.  High street prices do not always reflect a drug's "desirability" amongst substance users.  First of all, all pregabalin available on the street is diverted from the pharmacopeia. Second, the market is probably very small, meaning the street prices are inefficient.  Third, the retail cost of pregabalin (Lyrica branded by Pfizer here in the US) is quite high to begin with.  

We track the street prices of many drugs, especially opioids, in the hope of finding some interesting trends in the data.  For example, oxycodone in the US sells for 1 US dollar/mg almost everywhere - from New York City to rural North Dakota.  Hydrocodone sells for about $0.50 a milligram.  Buprenorphine sells for $1/mg - but it is not sought out for its abuse potential, rather for heroin or oxycodone dependent patients (DSM 304.xx) who are (a) trying to stop using those more dangerous drugs, or more often (b) trying to "bridge" the gap when they temporarily lose access to stronger opioids of choice.  An $8 pill of buprenorphine/naloxone (Suboxone as branded by Reckitt Benckiser) will keep an opioid dependent patient from getting sick for 24-36 hours while he or she seeks out oxycodone/diacetylmorphine/hydromorphone -- or other Schedule 2 opioids.  I think you are right that, in general, street prices reflect "desirability" or "abuse potential" but there are exceptions to that rule -- and market forces.  For example, heroin is much cheaper here in the US because it is in abundant supply -- and because it (usually) requires IV administration, whereas oxycodone has high bioavailability when taken PO.  Unfortunately, many patients shift to IV heroin when they can no longer afford PO oxycodone (of course, oxycodone can also be insufflated or administered IV) but here it is much more expensive than the morphine-equivalent dose of heroin.  

From anecdotal clinical reports, we have not heard of patients who seek out pregabalin on the street.  The situation must be different in Berlin.  Do you happen to know how much pregabalin costs on the street in Germany?  

I just ask because here in the US pregabalin is regarded as a pretty safe drug, with almost no mortality risk, and also little abuse potential.

Very best regards,

Devin

Dear Devin,

we will have to wait für further investigations... today i started to prescribe pregabalin for a patient willing, but still not able to stop diazepam-use. until now she tried hard, but coulndt stop for langer then some weeks.

best regards

chaim

Well, I wish your patient the best.  Have you seen Dr. Heather Ashton's Guide to Benzodiazepine Withdrawal - at http://www.benzo.org.uk/manual/ ?  She's at the Neuroscience Institute at the University of Newcastle in the UK, but the Guide is very practical - it is written for patients as well as physicians.  Interestingly, it advocates substituting diazepam for any other benzodiazepine and then VERY SLOWLY tapering off.  Of course, very few pts who have been on benzodiazepines long-term (years) ever manage to stop taking them.  In the US, at least as of a few years ago, diazepam was THE MOST PRESCRIBED controlled substance nationwide (measured by number of prescriptions written).  A really good Tx protocol is desperately needed for patients who want to withdraw from benzodiazepines -- I think that pregabalin will help, and that because pregabalin withdrawal causes much less discomfort than diazepam withdrawal, your patient may be able to stop taking any tranquilizer/neuroleptic after some months/years.  

Thank you very much, Devin! 

this manual at http://www.benzo.org.uk/manual/ is realy interesting and quiet important for every clinician confronted with benzodiazepine addiction!

we often used oxazepam, because its easy to control in oral fluid how much the patients realy use.

chaim

Devin Hosea, a really interesting question and discussion that followed it. As your question allows for sharing personal experience in addition to empirical evidence let me add few points:

1. We (a tertiary addiction medicine centre in Southern part of India) have been using Pregabalin in doses of 300-600 mg per day almost always giving a timed release preparation for high dose Benzodiazepine dependence. Our experience is that it allows a faster tapering of Diazepam dose. In this group of patients we have rarely encountered abuse of Pregabalin.

2. Another observation - Pregabalin has proved to be useful in two completely distinct types of Opioid users. Firstly, we have used it in patients having low dose opiate abuse (Poppy husk tea/Poppy husk joints). This group of patients usually do not qualify for Buprenorphine maintenance treatment but require extended pharmacological management of withdrawal and craving. Such cases are usually helped with Pregabalin along with other symptomatic treatments. 

Another group of patients that benefit with Pregabalin are chronic high dose heroin abusers who have withdrawal symptoms despite maximum Buprenorphine dose (32-34mg). Since Methadone is not available in our country we have found that Pregabalin acts as an augmenting agent.

Coming to the other part of discussion - evidence does suggest that Pregabalin may have a facilitatory role in opioidergic pathways. For example it has an opioid sparing effect during post operative period. Does Pregabalin have addictive potential?? We have seen a couple of cases of Opioid users who went on to abuse Pregabalin when opioids were not available. One of these cases with Gabapentin abuse was reported. 

A 2004 document submitted by Pfizer to FDA actually clearly states the euphorigenic effects of Pregabalin. Find the document attached.

However, the jury is still out on this one.

http://www.ncbi.nlm.nih.gov/pubmed/16846695

http://www.ncbi.nlm.nih.gov/pubmed/25716498

Are company reps pushing off-label use of Lyrica? What has been your experience?

No such experience with Pfizer reps - med will be generic in 2018 in US and already is so in Canada and elsewhere, so while Lyrica is expensive now it will certainly be less so by the end of the decade...and therefore an Rx:Tx possibility for detox and OST as lekhansh observes above. Very interesting that it is used for dependencies too low for buprenorphine maintenance.  What are pregabalin withdrawal symptoms like if any?  Gabapentin dep interesting. See article in this month's Addiction (UK/SSA) on gabapentioid addiction. I was not impressed and I'm writing letter expressing my view that study was deficiency was troublesome. My view: don't let the best be the enemy of the good. Authors were advising prescribers to avoid GP...but we know it's mild and could be a good OST or PAWS med. I think most clinicians would prefer their patients be on gabapentioid (Gapapentin/and/or/Pregabalin) than on...diamorphine, oxycodone, etc. have yet to hear of a *purely* GP-induced mortality. ALso it might be a good BST - bento substitution therapy. In my view barbiturates:benzos as benzos:gabapentioids. 

Sorry for late access to the discussion. I wanted to add some practical remarks. In our department detoxifications from benzodiazepines and Z-drugs are routinely conducted, following the method we have been developing for ten last years. As time passes and we grow in popularity, some other-drug addicted patients come and ask for help. Among them we meet patients addicted to pregabaline. I think their amount is underestimated because many symptoms secondary to addiction are taken for symptoms of their primary (psychiatric) illness. It is to note that apart from neurological applications and treatment of neuropathic pain, for some recent years pregabaline has been promoted as a new line of treatment of anxiety and mood disorders. Following such a treatment, after an initial improvement some patients experience spectacular exacerbation of the illness (as they think), because of a relapse and then an increase in intensity of  the former (as they think) symptoms or even due to onset of quite new ones. The symptoms actually result from increased tolerance and growing demand to the drug. Since these symptoms include (among others) fear, anxiety or agitation, they mimick the primary illness and even psychiatrists often do not associate them with possibility of drug dependence.  Like in case of Z-drugs, the pregabaline withdrawal symptoms are quite similar to those occurrying in benzodiazepine withdrawal. There are some more examples of non-BZD OUN-depressants which may cause dependence and worsen the course of a primary illness, for example baclofen. The similarities in symptoms and course of addiction seem transcend differences in receptor affinities (GABA-A vs. GABA-B) among these substances. Furthermore, after typical detoxification procedure (conversion q.s. into long-acting weak benzodiazepine, such as diazepam, and then controlled tapering up to zero serum level), the pregabaline patients achieve definite relief of symptoms. 

I do not claim against pregabaline at all, of course, as it is apparently useful medication. But we should still keep in mind that possibility of involuntary addiction is quite real, in order to apply pregabaline with caution, and in order to know what is happening and what to do if certain (withdrawal) symptoms occur.

What should I do for Clonotril veithdrawal?

With regard to question regarding Clonitril (clonazepam) withdrawal, I would refer you to PRof Heather Ashton’s www.benzo.org.uk/manual/bzsched.htm. Bottom line: very slow taper (if daily dose > 3mg you are talking many months, perhaps a year) then switch to diazepam at appropriare time. The whole protocol is explained on Ashton’s website above.