Need help Lorazepam and Tramadol dosage

[delphinen]

I have a very high benzo tolerance, and have been doing this kind of combo for years, sometimes with Codeine instead of Tramadol, sometimes with SOMA, sometimes with Lyrica, etc.

Today I find in an oddly situation for me. I know that 6-7mg Alprazolam is my "common dose" when doing 500mg Tramadol, but I am not too familiar with Lorazepam, last time I did some, I found it better than any other benzo to fall asleep, even if Clonazepam and Alprazolam are supposedly more powerful this was very weird for me.
So, could you guys help me? How much Lorazepam should I take and how I should time it?

Thanks in advance.

 

[Venrak]

I would take the lorazepam separately before combining it with the Tramadol.

An equipotent dose would be around 10mg, but that is a hell of a lot of lorazepam, so I would start somewhere around 4-5mg loraz alone.

Once you get a feel for it you will be able to begin thinking of mixing it with an opiate.

Also, note that your Tramadol dose is quite high and carries a greater seizure risk, as all doses above 400mg do.

 

[pasha]

Taking the lorazepam with the tramadol is a good idea, as it dramatically reduces the risk of a seizure. Lorazepam is equal to alprazolam (xanax) milligram per milligram. So 1 milligram of lorazepam, would be equivalent to 1 milligram of alprazolam.

When you take the lorazepam, make sure that it's in divided doses throughout the entire duration that the tramadol is active. If this is immediate release tramadol, than it will probably be active for 12-16 hours. Lorazepam's half-life is 12-16 hours with a duration of action that is usually anywhere between 6-12 hours. So to be on the safe side and to have the lorazepam working for the entirety of the possible 16 hours that the tramadol will be working, you will need to take 3 divided doses of lorazepam, one every ~6 hours.

The dosage that you will take in each of the three divided doses is dictated by you, and your tolerance to benzodiazepines. As I mentioned before, lorazepam is equally potent milligram to milligram with alprazolam, and clonazepam, but only with a shorter half-life and duration of action.

 

[Venrak]

Even though lorazepam raises the seizure threshold there isn't any concern of overpotentiation?

 

[pasha]

Tramadol is probably the only opioid where one could safely recommend it to be mixed with benzodiazepines. IME the CNS depression is almost non existent with tramadol, and the risk of an overdose from mixing it with benzodiazepines is highly improbable. I'm yet to come across an anecdote or a clinical report where this was the case. In the end of the day, the drug is both a stimulant and depressant, and by comparison to other opioids such as morphine, it is a weak depressant to say the least.

The bottom line for me is, mitigating the risk of a seizure with tramadol, something which is extensively established in literature, far outweighs the risk of additive CNS depression, something which is non-existent (at least to my knowledge) in literature.

 

[delphinen]

Thank you guys. I thought 10mg Valium was 1mg Lorazepam, and 0.5 Clonazepam and Alprazolam.

Anyway, the fact that I am taking both a powerful benzo (Alprazolam) and a sedative/hypnotic (Lorazepam) wouldn't help me to enjoy more the 500mg Tramadol from getting too stimulated or unable to sleep because of the SNRI properties?

 

[pasha]

Well you'll find different equipotency charts everywhere, but generally it's accepted that:

10 milligrams diazepam = 0.5 milligrams clonazepam= 0.5 milligrams alprazolam = 0.5 milligrams lorazepam.

Some people will argue that diazepam is more potent than these charts give it credit for, so the 10 milligrams can be substituted for 5. One must also remember that these charts are definitely not set in stone, and are just rough guidelines to go by. Each benzodiazepines affects each individual differently.

Benzodiazepines inhibit nor-epinephrine which effectively halts the SNRI properties of tramadol if the benzodiazepine dose is too high. It's all about getting your balance right with the benzodiazepine and the tramadol, if you wish to preserve the stimulating properties.

 

[delphinen]

Inhibiting norepinephrine halts the SNRI properties? that's the first time I read that, awesome information, thanks a lot.
So I could take a couple more a little more Tramadol as long as I keep taking Alprazolam and Lorazepam in high doses right?

 

[Venrak]

That's the way it sounds. But you will have to be, as you said, on high doses of benzos.

 

[bronson]

I certainly don't think that increasing doses of tramadol any higher than those you are already taking is advisable. You're already more or less at the ceiling dose as far as euphoria goes. Yes, benzos help counter the seizure risks, but as doses go up this becomes a balancing act that's hard to maintain.

CNS depression will eventually start to become an unquestionable concern. Consider also that on enough benzos there is the potential to stop caring about keeping the dosing intervals where they need to be.

This is a less is more situation. Play it safe.

 

[Swimmingdancer]

Tramadol is probably the only opioid where one could safely recommend it to be mixed with benzodiazepines. IME the CNS depression is almost non existent with tramadol, and the risk of an overdose from mixing it with benzodiazepines is highly improbable. I'm yet to come across an anecdote or a clinical report where this was the case.

I know that when taken on it's own in normal therapeutic doses Tramadol causes very little respiratory depression. But I have seen case reports of tramadol overdoses where it was taken with benzos. I have seen some studies where tramadol was combined with benzos with no significant respiratory depression or adverse events, but these were very small doses of each. Recreational use is less clear. And it's possible that combining tramadol + benzos could lead to adverse effects aside from just respiratory depression.

Fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality?

...possible interaction with other central nervous system (CNS) depressants, particularly benzodiazepines. ...a possible cytochrome P450-based interaction between tramadol and benzodiazepine is considered. [source]

All [tramadol] poisoning cases that admitted to Loghman-Hakim Hospital Poison Center [Iran] from April to May 2007 were studied. A total of 114 cases... Other illicit drugs were found to be used in combination with tramadol in some of the cases, which among them benzodiazepines were the most common. Tramadol overdose has been one of the most frequent causes of drug poisoning in the country in the recent years. [source]

 

[pasha]

Yeah I'm not really too convinced. Both of them state an indefinite yet suspected cause, The first case study doesn't mention respiratory depression, only that enzyme P450 may possibly be implicated hence why the title of the case study is asking a question rather than making a statement. The second one done in Iran states tramadol poisoning as the cause, with benzodiazepines only existing in some cases to be responsible for overdoses. Both of those case studies don't provide full toxicology reports on both the overdoses that contained tramadol and benzodiazepines and the ones in which tramadol and "other" substances were involved. It's difficult to get a clear picture without knowing the doses ingested, and any other substances that were ingested in both cases. These case reports are somewhat of a rarity if not the only ones which can be found, and anecdotes of overdoses from respiratory depression are nowhere to be seen for me. I'd like to see ones which are more definitive in order for me to be convinced that it's as dangerous as these authors suspect.

I've looked at another full report (an extension from the one you mentioned) on all the cases of overdoses which is slightly more detailed, but not fully, which was conducted in Iran also, and more than 55% of the patients (out of 1100 patients) in that case study were ingesting between 1000-5000 milligrams of tramadol. Suicide accounted for more than 50% of the patients involved, with seizures occurring in 45% of all the patients involved. Again it mentions co-ingestion with benzodiazepines without any specific number. In 70% of the cases of mortality seizures were observed. So with that in perspective regarding seizures accounting for most of the deaths, I think it would be safe to say that benzodiazepines would have been a more than appropriate preventative measure.

This is what it says on most tramadol datasheets:

toxic doses of tramadol could be suppressed with barbiturates or benzodiazepines, but were increased with naloxone. If convulsions are observed, diazepam should be given intravenously.

All case reports of serotonin syndrome/or tramadol induced seizures were controlled with benzodiazepines.

I find it slightly improbable for one to be able to definitely implicate tramadol and benzodiazepines, since tramadol does not cause respiratory depression (the studies I've shared with you and Venrak), and has very weak affinity for the opioid receptors, unless the doses of each drug were taken in extreme excess. I would even go as far as saying tramadol is more of a stimulant or an SNRI than it is an opioid. It's like venlafaxine with a touch of codeine. In the case of the OP, her dose is 100 milligrams above the daily recommended dosage, and some people get prescribed more than 600 milligrams of tramadol in nations were typical opioids don't exist, in which the risk of seizures is comfortably controlled using sedatives.

Even if the dose was high IME the risk of seizure far outweighs that of an overdose due to respiratory depression and the threshold which one can push the mixture of both drugs is marginally higher than with typical opioids. Maybe I'm wrong but I'd like to see more concrete information on the subject.

I see it this way, with all the information we have on tramadol, what's more likely, a seizure, or a fatal overdose from respiratory depression? A seizure, and the only way to negate that risk is by using benzodiazepines.

 

[Gator]

I would like to share my experience with tramadol.

At the height of my drug abuse, I was taking literally 40+ 50mg tramadol tablets per DAY. It eventually came to a head when I had a seizure while talking to my wife. I was unconscious for several minutes (but still retained much of my senses!), and it broke my heart to hear the love of my life begging me not to die.

That being said (and someone please correct me if I'm wrong) but I believe the benzo's should actually prevent the seizures. I also remember reading something that anything over 14 tablets (700mg) puts you at risk for seizures.

 

[Venrak]

^That's horrible I'm glad you worked your way through it.

The generally accepted daily dose at which an individual puts himself at greater risk of seizure is 400mg.

 

[Swimmingdancer]

it's possible that combining tramadol + benzos could lead to adverse effects aside from just respiratory depression.

Yeah I'm not really too convinced. Both of them state an indefinite yet suspected cause, The first case study doesn't mention respiratory depression, only that enzyme P450 may possibly be implicated hence why the title of the case study is asking a question rather than making a statement. The second one done in Iran states tramadol poisoning as the cause, with benzodiazepines only existing in some cases to be responsible for overdoses. Both of those case studies don't provide full toxicology reports on both the overdoses that contained tramadol and benzodiazepines and the ones in which tramadol and "other" substances were involved. It's difficult to get a clear picture without knowing the doses ingested, and any other substances that were ingested in both cases. These case reports are somewhat of a rarity if not the only ones which can be found, and anecdotes of overdoses from respiratory depression are nowhere to be seen for me. I'd like to see ones which are more definitive in order for me to be convinced that it's as dangerous as these authors suspect.

I've looked at another full report (an extension from the one you mentioned) on all the cases of overdoses which is slightly more detailed, but not fully, which was conducted in Iran also, and more than 55% of the patients (out of 1100 patients) in that case study were ingesting between 1000-5000 milligrams of tramadol. Suicide accounted for more than 50% of the patients involved, with seizures occurring in 45% of all the patients involved. Again it mentions co-ingestion with benzodiazepines without any specific number. In 70% of the cases of mortality seizures were observed. So with that in perspective regarding seizures accounting for most of the deaths, I think it would be safe to say that benzodiazepines would have been a more than appropriate preventative measure.

This is what it says on most tramadol datasheets:



All case reports of serotonin syndrome/or tramadol induced seizures were controlled with benzodiazepines.

I find it slightly improbable for one to be able to definitely implicate tramadol and benzodiazepines, since tramadol does not cause respiratory depression (the studies I've shared with you and Venrak), and has very weak affinity for the opioid receptors, unless the doses of each drug were taken in extreme excess. I would even go as far as saying tramadol is more of a stimulant or an SNRI than it is an opioid. It's like venlafaxine with a touch of codeine. In the case of the OP, her dose is 100 milligrams above the daily recommended dosage, and some people get prescribed more than 600 milligrams of tramadol in nations were typical opioids don't exist, in which the risk of seizures is comfortably controlled using sedatives.

Even if the dose was high IME the risk of seizure far outweighs that of an overdose due to respiratory depression and the threshold which one can push the mixture of both drugs is marginally higher than with typical opioids. Maybe I'm wrong but I'd like to see more concrete information on the subject.

I see it this way, with all the information we have on tramadol, what's more likely, a seizure, or a fatal overdose from respiratory depression? A seizure, and the only way to negate that risk is by using benzodiazepines.

Those are all good points and in general I agree with you. I wish I could see the full text of those articles. I was just saying that just because normal doses of tramadol don't tend to cause substantial respiratory depression doesn't necessarily mean that it's always a wise idea to mix tramadol and benzos, or that it carries no risks at all. You can have a serious tramadol overdose from effects other than just seizures or respiratory depression. Tramadol overdose can cause things like organ failure, serotonin syndrome, shock, heart failure, etc. Benzos might interact with tramadol in some way other than respiratory depression. It's unclear. And taking benzos alongside tramadol doesn't make it safe to take high doses.

Here is a case report where someone's breathing and heart stopped after taking tramadol (unfortunately the dose is unknown and was likely very high).

He was prescribed tramadol 100 mg qid [but] the exact amount of tramadol taken remains unknown. He is not known to have taken any other analgesics. His only other regular medications were prednisolone 20 mg and azathioprine 100 mg daily, both of which he had been taking for 8 weeks for fibrosing alveolitis. Both drugs were discontinued at the outpatient review due to a lack of response, the steroids by means of a reducing course. Biochemistry revealed no elevation of liver enzymes during this period. Alcohol history was unknown. Eight days following his outpatient visit, he was admitted
to hospital with increasing dyspnoea. On examination, he was drowsy, centrally cyanosed and hypotensive. Laboratory
investigations revealed markedly deranged liver tests, hypoxia, lactic acidosis and hypoglycaemia. Soon after
admission, he suffered a cardiorespiratory arrest and died. Toxicological analysis revealed a blood tramadol concentration of 3.7 mg/L, at least 12 times the normal therapeutic range of 0.1–0.3 mg/L [NOTE: I disagree with this, blood levels are highly variable and just 50mg of oral tramadol can give blood levels of up to 2mg/L - SD.]. Analyses for alcohol, paracetamol, barbiturates, antidepressants and other opiates were negative.

Here's a case report about someone mixing tramadol and benzos:

A 33-year-old man was admitted in our intensive care unit for drug intoxication with coma, seizures, and hypotension without signs of heart failure. A few hours later, he developed a ventricular tachycardia, followed by a brief cardiac arrest in asystole with refractory shock requiring an extracorporeal life support, vasopressors, and hemofiltration. With this aggressive support, his overall status gradually improved. Repeated echocardiography showed an improvement in the cardiac function. The patient was weaned off extracorporeal life support on day eight and discharged on day 12. On admission, a urine analysis, using gas chromatography-mass spectrometry, showed high peaks of tramadol and desmethyltramadol with the presence of hydroxyzine, gabapentine, and clonazepam. The tramadol blood concentration measured by the high-performance liquid chromatography method-diode array detector was 23.9 mg/L, much higher than many previously reported fatal overdoses. No other drugs with potential cardiac toxicity, such as beta-blockers, calcium antagonists, antiarrythmic, antidepressants, meprobamate, or other xenobiotics were detected. Conclusion. This case illustrates that tramadol overdose may cause refractory shock and asystole when taken in combination with CNS depressants, and reminds all physicians to be vigilant with regard to the potential toxic effects of tramadol.

Even though their conclusion is that the OD may have been due to mixing tramadol with CNS depressants, it's also possible that he would have had the same problems with those high blood levels of tramadol alone, or even that the clonazepam and gabapentin might possibly have reduced the severity of his overdose in some way.

Here's a study which said subjects using IV tramadol for analgesia had a significant drop in respiratory rate.

Anyway, not saying the OP should be worried, just saying I think in general it is prudent to still advise some caution when mixing benzos and tramadol, or tramadol and other opioids, and for people not to think that they can take high doses of tramadol just because they take benzos. I think it's an interesting discussion.

 

[pasha]

Anyway, not saying the OP should be worried, just saying I think in general it is prudent to still advise some caution when mixing benzos and tramadol, or tramadol and other opioids, and for people not to think that they can take high doses of tramadol just because they take benzos.

I certainly agree there. No matter what the opioid is, mixing a sedative and an opioid should always be exercised with some caution.

If you happen to find anymore case studies please share.