Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials John Girvan McConnell Ulster Hospital, Care of the Elderly, Dundonald, Belfast. E-mail: [email protected] Other Sections▼ REFERENCES I investigated reports of an abnormally high incidence of adverse reactions to fluoroquinolone antibiotics in patients dependent on and withdrawing from benzodiazepines. Participants of an online benzodiazepine withdrawal support group (www.thetrap.org.uk) who reported fluoroquinolone use were asked to fill out a structured questionnaire. Eleven participants reported severe or very severe adverse reactions, one participant reported a moderate adverse reaction, and a further participant reported no reaction to fluoroquinolone treatment. In most cases adverse symptoms resolved within 1 month of cessation of fluoroquinolone dosing. However, in some cases the symptoms persisted with gradual improvement for a period of several months. All participants reported adverse effects similar to those of acute benzodiazepine withdrawal which included depression, anxiety, psychosis, paranoia, severe insomnia, paraesthesia, tinnitus, hypersensitivity to light and sound, and tremors. Four patients became acutely suicidal.One participant, a female aged 44 years, who had detoxed off high prescribed doses of benzodiazepines 3 months previously, experienced an acute psychotic reaction within 1 hour of commencing norfloxacin and attempted suicide. Her condition quickly deteriorated and she developed repeated seizures; this progressed to status epilepticus, which failed to respond to treatment in ICU. Worryingly, her medical attendants continued to prescribe norfloxacin while in ICU. Her seizures were only controlled after finishing her norfloxacin course.Chronic use of benzodiazepines causes compensatory adaptions which cause GABA receptors to become less sensitive to GABA. On discontinuation of benzodiazepines, withdrawal symptoms typically develop which may persist for weeks or months.1 Antagonism of the GABAA receptor is believed to be responsible for the CNS toxicity of fluoroquinolones affecting 1�4% of patients treated.2 Fluoroquinolones have also been found to inhibit benzodiazepine receptor binding.3 The results of this small study seem to confirm that adverse reactions to fluoroquinolones occur more frequently in the benzodiazepine-dependent population than the 1�4% seen in the general public and may be severe.Possible explanations for the adverse fluoroquinolone-induced reactions in the current reported patient group include: �Fluoroquinolones compete directly with benzodiazepines for the benzodiazepine receptor site displacing benzodiazepines and precipitating an acute withdrawal effect. �Alterations in the GABAA�benzodiazepine receptor complex (during benzodiazepine tolerance/dependency status) may increase fluoroquinolone-induced stimulation of the receptor complex. �Benzodiazepine dose-tapering and/or cessation might be associated with GABAergic underactivity but rebound neuro-excitation following fluoroquinolone exposure. Participants were asked in the questionnaire about medication and alcohol or drug usage at time of adverse reaction. None of the participants reported anything which could explain their adverse reaction apart from the introduction of a fluoroquinolone. Physicians should, wherever possible, avoid fluoroquinolones in patients who are dependent on or withdrawing from chronic benzodiazepines.
Posted by Stefan (Member # 19150) on :
I did Lorazepam with levofloxacin. Anyone else too quinolones and benzodiazepines togeteher?
Posted by Dawn in VA (Member # 9693) on :
Oh crap! Like you, I did too.
This is a very interesting and informative post. Thank you so much for listing it.
Posted by jwall (Member # 22999) on :
I'm scared. I am supposed to be on IV levaquin next month. I had a terrible withdrawal experience from just one month of taking klonopin!! I have been thoroughly warned (by the benzo withdrawal community...yes, there is an entire forum just like this one for benzo sufferers) to steer clear from this class of antibiotics. Too bad our doctors don't about this interaction and we have to find out the hard way!!!!
Even one year after withdrawing, I am still experiencing adverse effects from klonopin! They are right when they say withdrawal effects can last weeks to months...not for everyone, just for an unfortunate percentage.
Posted by 'Kete-tracker (Member # 17189) on :
THANKyou for posting this, Stefan.
I've been on lo-level doses of lorazepam for years now to occasionally help with sleep.
And here I'd of prescribed myself (if I Could) some levofloxacin for a month or so to see if it took care of- or improved- my remaining peripheral neuropathy, which I've been alternately blaming on an untreated BLO co-infection... or unresolved Lyme in the neuro-bundles. (The former is considered best treated with "levo" according to Dr. B's guidelines).
Never was made aware of the possible incompatibility between the 2 groups of drugs before. Didn't realize there might be such a serious potential of messing with my "state of mind"! Posted by Stefan (Member # 19150) on :
Hi Kete -tracker - where do you have your peripheral neuropathy?
Posted by 'Kete-tracker (Member # 17189) on :
Currently lower arms & slightly in the mid-legs. But it's migrated... Twice! Started spreading down the arms SLOwly, back about 2 months into my initial treatment for the acute Lyme (post-diagnosis).
As the "fuzziness" reached my hands (Only really noticable just after awakening- never present during the day), I noticed [hey!] my knuckles were reddened, esp. where the early-AM numbness was worst.
By the time I was back to normal energy levels & enjoying life again (about 6 l--o--n--g months after this) the early-AM numbness was confined to my hands, but would magically 'vanish' over just a minute or 2 after waking up. But I could still move my hands & fingers just Fine even with severe local "fuzz"... not a cut-off circulation issue. The reddened knuckles? They'd fade over 5 to ~15 minutes. I just ignored it all.
Then, just about 15 months later, this 'upon-awakening Numbness' started slowly spreading back UP each arm... until it involved the whole appendage! Went back to my LLND. We upped support for nerve repair & started c.silver.
Within a couple weeks after That, I noticed my legs were also getting a little fuzzy (1st time!) mostly between mid-calf & just below the knee. The feet have never been involved.
I've shown pics I've taken at 5AM of the reddened knuckles to my LLMD & LLND, as well as explained ALL of this to 'Dr. R' of NYC one eve, but they're all stumped. I still remember Dr R's initial comment: "That's Odd." (S%#$! And he was my best hope.)
Dr. R thinks it's NOT Lyme but likely a "co-" that was never addressed & recommended further blood tests. I'll have 'em run by my LLND when I have the $$.
Sorry for such a long answer. Maybe a medical person might chime in here. Posted by Stefan (Member # 19150) on :
Anyone else used quinolones and higher doses of benzodiazepines togeteher?
And hopefully did not had withdrawal symptoms.
Posted by Stefan (Member # 19150) on :
I am asking this because I am on benzos and cannot quit them so fast, but levofloxacin helps best for my back pain...and i want to use it again even with benzos together. The last time i took them together I had no problems. Please tell me your experiences..
Posted by feelfit (Member # 12770) on :
Have been on klonopin for years. low dose, .50 mg.. Have also been on Levaquin for short periods about 3 times. I am currently on my 3rd attempt with levaquin and still taking .50 klonopin daily.
the only brain sx. that i notice is restless sleep. Taking Levaquin early in the day can help with the restless sleep issue.
Posted by Stefan (Member # 19150) on :
anyone elsecan share their experiences?
Posted by Stefan (Member # 19150) on :
Bump ! Wanted to know if somebody else tokk benzodiazepines in Combination with Levofloxacin or other quinolones and had side effects? (withdrawal symptoms?)
Posted by Stefan (Member # 19150) on :
Bump ! Wanted to know if somebody else tokk benzodiazepines in Combination with Levofloxacin or other quinolones and had side effects? (withdrawal symptoms?)
Posted by Stefan (Member # 19150) on :
@Dawn in VA - your mailbox is full
You wrote you took benzos and levofloxacin or quinolones together?
May I ask you which dosage of benzos and which type and for how long together with quinolones?
Did you had withdrawal symptoms?
You wrote : Oh crap! Like you, I did too.
Posted by seibertneurolyme (Member # 6416) on :
Hubby has been on ativan -- doses from 4 mg orally up to 8 mg IV (in hospital) while taking both levaquin and factive. He decreased his ativan from 4 mg daily to 1/2 mg daily over 8 months in 2010 before he had a symptom crash and was put back on 4 mg daily. He was on the levaquin for about 8 months I think and the factive for about the same.
Hubby has been on the ativan in varying doses for a total of at least 7 years while treating tickborne infections. Used primarily for seizure-like issues (in the past none of the half a dozen seizure-meds he tried helped). But he is currently taking low dose topamax as well as the ativan.
He has noticed no problems taking the ativan with either levaquin or factive. The factive especially actually seemed to lessen hubby's muscle and tendon pain.
Hubby also takes high dose passion flower extract for sleep. 5 -7 droppers nightly. This herb supposedly works on the Gaba receptors as well.
Bea Seibert
Posted by anjiell (Member # 28322) on :
i was on 2mg of lorazapam with my cipro treatment for a few months the only thing i noticed was increased rib cage burning and spine,which subsided and actually do not have many episodes of the rib cage anymore.as far as having neuro depression symptoms,not wanting to wake up to lyme anymore and increases with meds i just think that before i had a positive western blot i pretty much was out of my mind with lyme symptoms and i was on no treatment.i think lyme just messes with your head anyways.
Posted by Stefan (Member # 19150) on :
thanks alot for all your answers - ativan is the same as lorazepam as i see
I took levaquin with ativan 5 mg too and had no side effects.
I was just a little scared about the article above and i have to take it again.
Posted by Stefan (Member # 19150) on :
Another article which scares me....I can t go off the benzos quickly but need levaquin for bart.
"Fluorquinole antibiotics have been noted by Professor Heather Ashton and confirmed in a study as often causing serious complications in patients chronically taking benzodiazepines or undergoing withdrawal from benzodiazepines. This is probably the result of the GABA antagonistic effect of fluoroquinolones. Fluoroquinolones have also been found to competitively displace benzodiazepines from benzodiazepine receptors which can precipitate acute withdrawal symptoms in benzodiazepine dependent subjects. A study reported higher than usual CNS toxicity from fluoroquinolones in subjects who were dependent on or in withdrawal from benzodiazepines. Of the general public 1 � 4% of the public will experience CNS toxicity from fluoroquinolones which may be severe. The incidence of severe CNS toxicity occurs significantly more frequently in the benzodiazepine dependent population. The CNS adverse reactions from fluoroquinolones were similar to those seen in benzodiazepine withdrawal and persisted for weeks or months before subsiding. The symptoms included depression, anxiety, psychosis, paranoia, severe insomnia, parathesia, tinnitus, hypersensitivity to light and sound, tremors, status epilepticus, suicidal thoughts and suicide attempt. The study confirmed that fluoroquinolone CNS toxicity can be serious, occurs more frequently in benzodiazepine dependent subjects and concluded that fluoroquinolone antibiotics should be contraindicated in patients who are dependent on or in benzodiazepine withdrawal. A person with an already compromised GABA system for example one going through benzodiazepine withdrawal is likely to be at an even greater risk of severe adverse reactions.[3][90][91][92][93] NSAIDs have some mild GABA antagonistic properties and some may even displace benzodiazepines from their binding site according to animal research. They do not cause as potent antagonism of GABA function as fluoroquinolones. However, NSAIDs taken in combination with fluoroquinolones causes a very significant increase in GABA antagonism which may result in very severe GABA antagonism, GABA toxicity, and seizures and other severe adverse effects (see fluoroquinolone toxicity).[94][95][96]"
Posted by Stacyb (Member # 13084) on :
I agree with Feelfit and have been on and off Benzo's with various Florquins and did not have the side effects that are stated.
I can say that the Levaquin must make the Benzos less effective and the Floroquins are know to disturb or effect sleep (quoted from my LLMD). In fact most Bart tx such as when I was on Rifampin had a reducing effect on the Benzos I took for sleep. I actually got better with sleep after many months from Rifampin and could sleep with out Benzos and just herbs/supplements.
For now I switch up Benzos with other Rx sleep meds and combine that with sleep supplements to help combat the effects of the Levaquin blocking the sleep meds. Also I do not take Benzos every night as I try and switch around to not become to dependent.
I took Zanax for almost 2 straight years when first in tx and went off almost cold turkey and did not have any of the mention with drawl symptoms.
I would suspect that if the Floroquins and Benzos compete for the same process pathway and interupt Gaba effect that maybe adding Gaba in to the mix can help this reaction too.
Posted by Stefan (Member # 19150) on :
Ty stacy for your reply .... just want us to feel secure ....didn t had withdrawal symptoms too...except some nerve stinging in in the face (cheeks) May I ask which doses you took?
Posted by Stefan (Member # 19150) on :
I cannot tolerate melatonin - but maybee its interesting for you R�sum� / AbstractAn open pilot study on the safety and efficacy of melatonin in the treatment of insomniac patients was conducted in 22 subjects (16 females), mean � S.D. age 60.1 � 9.5 years. All patients received 3 mg of gelatin melatonin capsules per os daily for 6 months, 30 min before expected sleep time. Twenty of 22 patients were on benzodiazepine treatment and they continued this treatment for part of or for the entire melatonin administration period. Serum concentrations of prolactin, follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), or estradiol were measured by radioimmunoassay (RIA) in morning samples at the beginning and after 6 months of melatonin administration, and standard clinical laboratory tests for blood components were performed. Urinary 6-sulphatoxymelatonin (aMT6s) excretion was measured by RIA before treatment. Serum concentrations of prolactin, FSH, TSH, or estradiol did not exhibit changes after 6 months of melatonin administration, nor were any indications of hematologic or blood biochemistry alteration found. Melatonin augmented significantly the quality and duration of sleep, and decreased sleep latency and the number of awakening episodes, as assessed from sleep logs filled by the patients (first 21 days) and from structured interviews performed by incumbent physicians (up to 6 months). Estimates of next-day function (i.e., alertness in the morning and during the day) also improved significantly during melatonin treatment. The observed effect lasted for the entire period examined (up to 6 months), with 22 out of 22 patients showing improved sleep at the end of treatment. The urinary excretion of aMT6s before starting administration of melatonin correlated negatively and significantly with age, but not with the intensity of sleep the disorder or the outcome of treatment. In 13 of 20 patients taking benzodiazepines together with melatonin, benzodiazepine use could be stopped, and in another four patients, benzodiazepine dose could be decreased to 25-66% of the initial dose. The results of this open, subacute administration trial indicate that melatonin is a safe and useful treatment for sleep disturbances in middle-aged or elderly patients, either by itself or together with benzodiazepines.
Posted by Stefan (Member # 19150) on :
How can we substitute gaba?
I would suspect that if the Floroquins and Benzos compete for the same process pathway and interupt Gaba effect that maybe adding Gaba in to the mix can help this reaction too.
Posted by annier1071 (Member # 28977) on :
I have take levaquin numberous times and have been on xanax for many years for menieres and vertigo. I never had an issue with the combination and was never told by any doctor that it would cause a problem.
I could be just that some cannot tolerate the two? I take 2 mgs a day to keep the nerves in my inner ear from fluttering.
Posted by Stefan (Member # 19150) on :
thanks for all your replies - strange on the one hand side that our doctors are not telling us about possible interactions...
Posted by Stacyb (Member # 13084) on :
Stefan,
Regarding dosage. I take 500 mg of Levaquin and 2 mgs of xanax.
I have taken Gaba and like a particular brand. Seems to really help with brain axiety and is suppose to be good for folks with seizures (info. from my LLMD). I forget the dose I was taking but it was rather high but did help a lot!
Posted by Stacyb (Member # 13084) on :
Stefan,
Regarding dosage. I take 500 mg of Levaquin and 2 mgs of xanax.
I have taken Gaba and like a particular brand. Seems to really help with brain axiety and is suppose to be good for folks with seizures (info. from my LLMD). I forget the dose I was taking but it was rather high but did help a lot!
Posted by Haley (Member # 22008) on :
I wanted to bring this back up to bring it to people's attention. I seem to be slipping into some kind of clinical depression. I do have some life stress such as a bad break up but I can feel that something physical is going on.
Of course, we have so many variables with this disease. I believe I am having this crazy severe depression and anxiety because I am on Levaquin every other day and I also take a benzo at night.
This warning is very real. Please pay attention. I feel so terrible. I'm stopping the Levaquin. Can't stop the benzo yet.
I believe this is what I am experiencing:
�Fluoroquinolones compete directly with benzodiazepines for the benzodiazepine receptor site displacing benzodiazepines and precipitating an acute withdrawal effect.
Posted by dian (Member # 14335) on :
Can someone please explain this to me in simple words, I am confused. I am currently taking 250mg levinquin daily along with ativan daily. Does this article mean that you should not be taking these two drugs together and if you do, what is happening. I don't understand that article, it is too complicated for me. Diana
Posted by Stefan (Member # 19150) on :
�Fluoroquinolones compete directly with benzodiazepines for the benzodiazepine receptor site displacing benzodiazepines and precipitating an acute withdrawal effect.
Posted by Haley (Member # 22008) on :
Diana,
You may feel ok while you are on the medicine but you may experience withdrawal type symptoms when you go off.
I was on Levaquin every other day. On my days off I felt SEVERELY depressed and agitated. All along I have attributed this to my break up and my illness but I could tell that there was something deeper. I remembered reading this about the combination of Lev with benzos. I have been off the Levaquin about four days and I am already feeling better.
You should be ok but if you experience crazy emotional ups and downs or severe insomnia, the Levaquin may be contributing to what you are experiencing. Just keep that in mind.
![[dizzy]](graemlins/dizzy.gif)
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until it involved the whole appendage! Went back to my LLND. We upped support for nerve repair & started c.silver.![[shake]](graemlins/shake.gif)
![[Wink]](wink.gif)