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Dr. Andrew Rynne

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Does regular intake of Modafinil result in brain aneurysm?

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Dr. Olsi Taka

Neurologist

Practicing since :2004

Answered : 1170 Questions

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Posted on Thu, 9 Mar 2017 in Brain and Spine
Question: Hello
Could taking 600-800mg at once of Modafinil (Provigil) on one or two occasions cause the artery walls in your brain to become inflamed/weakened/damaged? And could it create a brain aneurysm? (And could it affect your heart in any bad way?)
Does taking 600-800mg at once cause high blood pressure that is high enough to cause serious health problems such as a brain aneurysm?
And could, over several years, daily use of Modafinil (Provigil) at 400mg at a time help cause potentially serious brain or heart problems?
Many thanks XXXXXXX Harris
doctor
Answered by Dr. Olsi Taka 2 hours later
Brief Answer:
No aneurysm.

Detailed Answer:
I read your question carefully and I understand your concern.

That dosage of 600-800 mg is higher than the recommended one. However in terms of a brain aneurysm, of causing changes in the connective tissue of the blood vessels wall, it doesn't have any effect, no study has evidenced such an association. It changes neurotransmitter levels in the brain but doesn't affect the vessel walls or their innervation, hence no effect.
The same applies to long term use, may cause side effects such as headaches, nervousness due to changes in neurotransmitter balance, but no aneurysm.

As for effects on the heart, there is a slight risk of affecting heart rhythm, causing arrhythmias,fluctuations in blood pressure. They are not common though and usually reversible once interrupted.

I remain at your disposal for other questions.
Above answer was peer-reviewed by : Dr. Raju A.T
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Follow up: Dr. Olsi Taka 14 hours later
I understand “no study has evidenced such an association” however is that because a brain aneurysm/blood vessel wall damage is not possible or because not many studies have been done into the effects of the drug?

The drug can cause high blood pressure, does this make it capable in theory of causing brain aneurysm/blood vessel wall damage? And could the drug, at high doses, cause blood pressure to rise high enough to cause a brain aneurysm/blood vessel wall damage?

How is modafinil different to other stimulant drugs such as cocaine and amphetamines when it comes to the possibility of causing a brain aneurysm/blood vessel wall damage?

What is it that causes headaches when on this drug?

Can the possible effect on the heart that you mention be fatal in healthy individuals with a normal heart and normal ECG in the past?
doctor
Answered by Dr. Olsi Taka 1 hour later
Brief Answer:
Read below

Detailed Answer:
When I say no study has shown an association I mean that studies regarding brain aneurysms have not shown any association with modafinil use, no high percentage of modafinil users in aneurysm patients.
Whether the future may bring new evidence, of course that is possible. But that applies to every medication out there, to many foods we use or environmental factors etc, we can speak only about the current evidence.

Simply high blood pressure doesn't cause an aneurysm. An aneurysm happens in a particular site in the wall of a blood vessel, while high blood pressure effects are all along the blood vessel system. An aneurysm is created by a primary change in the blood vessel itself, not due to high blood pressure. High blood pressure may influence in increasing its size, but doesn't cause it alone.

Difference from cocaine and amphetamines, is that they have sympathomimetic effects acting directly on the wall of the blood vessels.

As for headaches, since it affects neurotransmitter levels it may cause headache. That applies to all drugs affecting central nervous system, it is listed as a possible side effect in all of them, even in some which are used for headache prevention it may cause headache instead. Doesn't mean it will necessarily happen of course.

As for heart effects, arrhythmia can potentially be dangerous so I can't exclude that, but in a healthy individual the risk is very low, under 1%.

Let me know if I can further assist you.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
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Follow up: Dr. Olsi Taka 1 hour later
Many thanks for that reply.

If you develop a headache after taking modafinil has that got anything to do with the drug's ability to cause high blood pressure?

Also, when used in recommended doses do amphetamines cause high blood pressure? And is a brain aneurysm/blood vessel wall damage a possibility with these drugs when they are used in their recommended doses either in the short term or long term? And are the risks to the heart the same with these drugs as they are with modafinil or worse?
doctor
Answered by Dr. Olsi Taka 9 hours later
Brief Answer:
Read below

Detailed Answer:
High blood pressure may cause headache, but headache may happen also with normal blood pressure. A measurement during headache would easily make the distinction.

Amphetamines can cause high blood pressure in a percentage of patients, even when in recommended dosages.

A brain aneurysm is not an issue if used only short term. When used long term it is more of an issue with amphethamines than it is with modafinil as they have more pronounced simpathomimetic effects and more of a direct influence on blood vessels walls.

The same applies to the heart, there is more of a risk with amphethamines, modafinil is safer.

I hope to have been of help.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Olsi Taka 39 hours later
Many thanks for that reply.

Are you able to provide any statistics on the risk of brain aneurysm/blood vessel wall damage and serious heart problems in people that use amphetamines in recommended doses over the long term?
doctor
Answered by Dr. Olsi Taka 44 minutes later
Brief Answer:
Read below

Detailed Answer:
Hello again.

I am not aware of any statistics and from quickly reviewing journal databases I confirm that there aren't any percentages regarding aneurysm development. There are only separate case reports. That makes sense as such an epidemiological study would be hard to conduct. Most aneurysms present no symptoms and would be detected only by vascular brain imaging interpreted by specialized neuroradiologists. So such a study would mean to conduct expensive imaging tests, with contrast administration to large groups of patients (thousands) under amphetamines. These tests would also need to be conducted on an equally large group of people not under amphetamines in order to compare results (as a percentage of the population does carry aneurysms anyway). So such studies are not feasible.
Because basic testing for heart issues is easier there are some more studies in that group. Even there it depends on definition of cardiovascular issues and confounding factors. That is as people using amphetamines have shown a higher percentage of other lifestyle issues affecting cardiovascular system, issues such as smoking, alcohol or other substance abuse, other medications, obesity etc. So depending on epidemiological methods results vary a lot and is not a completely resolved issue.
One study which might be referred to (Schelleman et al, XXXXXXX Journal of Psychiatry Feb 2012) puts incidence rate of sudden death or cardiac arrhythmia per 1000 person-years at 2.17 in users of an amphetamine such as methylphenidate compared to 0.98 in non-users. As I said though results vary depending on epidemiological methods.


Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
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Follow up: Dr. Olsi Taka 37 minutes later
Many thanks for that reply.

I would like to get you clarify something that you said in an earlier answer if that is alright. You said: "A brain aneurysm is not an issue if used only short term. When used long term it is more of an issue with amphethamines than it is with modafinil", are you saying that even when amphetamines are used in recommended doses and are not abused they can cause still brain aneurysms?

And as for the risks to the heart of amphetamine use, would regular ECG tests be enough to eliminate any risk of any serious heart problems?
doctor
Answered by Dr. Olsi Taka 54 minutes later
Brief Answer:
Read below

Detailed Answer:
My remark was mainly directed to abuse of cocaine and amphetamines, not to use in regulated dosages. In regulated dosages there is no proven risk to develop an aneurysm by epidemiological studies on aneurysm risk factors. That being said, given their mechanism of action I would still advise caution in people who have a predisposition for aneurysms such as a family history or connective tissue diseases. Aneurysms are not caused by one single factor, it is a question of a genetic predisposition upon which act outside environmental factors, so in predisposed individuals risk may be higher. Also in individuals who have an aneurysm (1.5 - 5% of individuals will develop an aneurysm during their lifetime) I would avoid use even in regulated dosage as amphetamine effect may accelerate growth and increase rupture risk.
Regarding EKG as screening, it may detect anomalies in a percentage of users, but doesn't serve as a guarantee, arrhythmias may be sudden or in short episodes with normal recordings in between.

Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
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Follow up: Dr. Olsi Taka 22 minutes later
And can the arrhythmias be fatal in healthy individuals with normal hearts/no heart problems?
doctor
Answered by Dr. Olsi Taka 4 hours later
Brief Answer:
Read below

Detailed Answer:
In theory yes, arrhythmia can at times be fatal. But before being alarmed at that try to keep things in perspective, look at that study I brought as an example. The added risk is of only one more case for 1000 person years, really small, means that in a population of 1000 patients taking the medication during the course of a year there will be only one more case of arrhythmia (2 cases in total compared to 1 in the 1000 patients not under treatment). Hope I was clear, perhaps not that good at explaining epidemiology.

Wishing you good health.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
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