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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by bethesdabob on November 3, 2004, at 17:22:55
Friend is epileptic, her shrink has her taking 600 mgs. of Effexor XR and 90 mgs of Remeron, googled the combination, understand that 225 mgs is max for the Effexor XR and 45 mgs tops for Remeron, also that high doses of effexor is proconvulsant, can anyone comment ?
Posted by linkadge on November 3, 2004, at 19:32:58
In reply to Proconvulsant - Effexor with Remeron ???, posted by bethesdabob on November 3, 2004, at 17:22:55
This combination sounds extremely pro-convulsant. Hopefully, she has some powerful anticonvulsants in place.
Linkadge
Posted by dove on November 4, 2004, at 10:36:22
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by linkadge on November 3, 2004, at 19:32:58
Excuse this stupid question, but, why is this combo proconvulsant??? Is it both meds or the meds singularly?
dove
Posted by bethesdabob on November 4, 2004, at 10:54:20
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by dove on November 4, 2004, at 10:36:22
What I am led to believe is that they work on different receptors in the brain, could cause a short circuit that could bring about a seizure.
Am no expert, just seeking to confirm or deny.
Posted by crazychickuk on November 4, 2004, at 11:06:18
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by bethesdabob on November 4, 2004, at 10:54:20
bloody hell wat is her doc thinking off...... wayyyy to much.. effexor is well known for making ppl experience electric shocks a bit like the start of a seizure... shows up on eeg's .. talk to her prin out some info for her to take to her doc .. bless
Posted by linkadge on November 5, 2004, at 10:16:56
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by crazychickuk on November 4, 2004, at 11:06:18
Most antidepressants are proconvulsant. Meaning that they lower the seizure threshold.
This is why anticonvulsants can tend to depress both the mood and nerve activiy.
Effexor and wellbutrin are the ones that lower the seizure threshold the most (next to some of the tryciclics) This effect is *generally* irrelevent unless you have seizure disorder.
Linkadge
Posted by bethesdabob on November 5, 2004, at 11:11:41
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by linkadge on November 5, 2004, at 10:16:56
Many thanks for the benefits of your insight, I lied to you folks, the person taking the combination was more than a friend, it was my wife.
Wife's psychiatrist treated her epilepsy and her bipolar, was taking trileptal and clonazepam for seizures, was taking 600 mgs of effexor xr and 90 mgs of remeron.
Wife had several small seizures that her shrink was aware of, last December while taking kids to school leaving her alone at home she had a major one and died, I discovered her dead body when I got home 45 minutes later.
Pathologist said that she died from a seizure disorder (SUDEP), it was suggested that I have a malpractice attorney look into her death. Last week was told by attorney that a psychiatrist had reviewed the records and thought this case had potential merit, but would not know of final decision until a pharmacologist and a neurologist reviewed the records.
Posted by ed_uk on November 5, 2004, at 12:55:17
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by bethesdabob on November 5, 2004, at 11:11:41
Here is a an abstract from a study which you may want to read. I have surrounded the most interesting sentences with stars.....
Braz J Med Biol Res. 2002 Apr;35(4):469-72. Related Articles, Links
Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats.Santos JG Jr, Do Monte FH, Russi M, Agustine PE, Lanziotti VM.
Laboratorio de Neurofisiologia, Departamento de Psicobiologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brasil. [email protected]
Venlafaxine, an atypical antidepressant drug, has been used to treat several neurological disorders, presenting excellent efficacy and tolerability. **Clinical seizures after venlafaxine treatment have occasionally been reported when the drug was used at very high doses or in combination with other medications.** The aim of the present study was to investigate the convulsant effects of venlafaxine in rats under controlled laboratory conditions. Adult male Wistar rats (8 per group) receiving venlafaxine or saline at the doses of 25-150 mg/kg were subjected 30 min later to injections of pentylenetetrazole at the dose of 60 mg/kg. The animals receiving 75, 100 and 150 mg/kg venlafaxine presented increased severity of convulsion when compared to controls (P = 0.02, P = 0.04, and P = 0.0004, respectively). Indeed, an increased percentage of death was observed in these groups (50, 38, and 88%, respectively) when compared to the percentage of death in the controls (0%). The group receiving 150 mg/kg showed an reduction in death latency (999 +/- 146 s) compared to controls (1800 +/- 0 s; cut-off time). Indeed, in this group, all animals developed seizures prior to pentylenetetrazole administration. Surprisingly, the groups receiving venlafaxine at the doses of 25 and 50 mg/kg showed a tendency towards an increase in the latency to the first convulsion. These findings suggest that venlafaxine at doses of 25 and 50 mg/kg has some tendency to an anticonvulsant effect in the rat, whereas **doses of 75, 100 and 150 mg/kg presented clear proconvulsant effects in rats submitted to the pentylenetetrazole injection.** These findings are the first report in the literature concerning the role of venlafaxine in seizure genesis in the rat under controlled conditions.
Some more info.........
From the textbook Martindale:
.....Venlafaxine should also be used with caution in patients with a history of epilepsy and should be discontinued in any patient developing a seizure.......
....Mirtazapine should be used with caution in patients with epilepsy........From the information provided in the British National Formulary (based mainly on the info given by the manufacturer)...
Cautions: history of myocardial infarction or unstable heart disease, blood pressure monitoring advisable if dose exceeds 200 mg daily, ***history of epilepsy***, mania, hepatic or renal impairment (Appendixes 2 and 3), avoid abrupt withdrawal (if taken for more than 1 week withdraw over at least 1 week); glaucoma; concomitant use of drugs that increase risk of bleeding, history of bleeding disorders; interactions: Appendix 1 (venlafaxine)
CSM advice on the potential for harmful outcomes in children and adolescents
DRIVING. May affect performance of skilled tasks (e.g. driving)
SKIN REACTIONS. Advise patients to contact doctor if rash, urticaria or related allergic reaction develops
Contra-indications: severe hepatic or renal impairment; pregnancy and breast-feeding
Side-effects: constipation, nausea; dizziness, dry mouth, insomnia, nervousness, drowsiness, asthenia, headache; sexual dysfunction; sweating; commonly anorexia, weight changes, diarrhoea, dyspepsia, vomiting, abdominal pain; hypertension, palpitation, vasodilatation, changes in serum cholesterol; chills, pyrexia, dyspnoea, yawning; abnormal dreams, agitation, anxiety, confusion, hypertonia, paraesthesia, tremor; urinary frequency, menstrual disturbances; arthralgia, myalgia; visual disturbances, mydriasis; tinnitus; pruritus, rash (see Skin Reactions above); less commonly bruxism, taste disturbances; postural hypotension, arrhythmias, syndrome of inappropriate anti-diuretic hormone secretion (see advice on Hyponatraemia); hallucinations, myoclonus; urinary retention; bleeding disorders (including ecchymosis and rarely haemorrhage); hypersensitivity reactions including angioedema, urticaria, photosensitivity; rarely ataxia, incoordination, speech disorder, extrapyramidal effects, mania and hypomania, ****seizures****, serotonin syndrome; galactorrhoea; thrombocytopenia; erythema multiforme, Stevens-Johnson syndrome; hepatitis reported
Dose: depression, initially 75 mg daily in 2 divided doses increased if necessary after several weeks to 150 mg daily in 2 divided doses; child and adolescent under 18 years not recommended (see CSM advice on the potential for harmful outcomes in children and adolescents)
Severely depressed or hospitalised patients, initially 150 mg daily in 2 divided doses increased if necessary in steps of up to 75 mg every 2–3 days to ****max. 375 mg daily**** then gradually reduced;Cautions: ****epilepsy****, hepatic or renal impairment, cardiac disorders, hypotension, history of urinary retention, angle-closure glaucoma, diabetes mellitus, psychoses (may aggravate psychotic symptoms), history of bipolar depression, avoid abrupt withdrawal; manufacturer advises avoid in pregnancy and in breast-feeding (Appendix 5); interactions: Appendix 1 (mirtazapine)
BLOOD DISORDERS. Patients should be advised to report any fever, sore throat, stomatitis or other signs of infection during treatment. Blood count should be performed and the drug stopped immediately if blood dyscrasia suspected
Side-effects: increased appetite and weight gain, oedema, sedation; less commonly dizziness, headache; rarely postural hypotension, abnormal dreams, mania, ****convulsions****, tremor, myoclonus, paraesthesia, arthralgia, myalgia, restless legs, exanthema, reversible agranulocytosis (see Cautions above)
Dose: initially 15 mg daily at bedtime increased according to response ***up to 45 mg daily*** as a single dose at bedtime or in 2 divided doses; child not recommended
From the product data sheets provided to the British authorities by the manufacturer:
.....Efexor XL should be introduced with caution in patients with a history of seizure and should be discontinued in any patient developing a seizure......
NB. Efexor is the English spelling for effexor.Neurological adverse effects of effexor..
Neurological disorders - Very common: dizziness, dry mouth, insomnia, nervousness, somnolence; Common: abnormal dreams,agitation, anxiety, confusion, hypertonia, paraesthesia, tremor; Uncommon: hallucinations, myoclonus; Rare: ataxia anddisorders of balance and co-ordination, speech disorders including dysarthria, extrapyramidal disorders includingdyskinesia and dystonia, mania or hypomania (see Special Warnings and Special Precautions for Use), neuroleptic malignant syndrome-like effects, ***seizures*** (see Special Warnings and Special Precautions for Use), serotonergic syndrome; Very rare: delirium.Dose, note that the maximum licensed dose of effexor XR is 225mg whereas the maximum dose for effexor is 375mg......
For initiation and maintenance the recommended dose for depressive illness for Efexor XL is 75mg, given once daily. Antidepressant activity with the 75mg dose was observed after 2 weeks of treatment. If after 2 weeks further clinical improvement is required, the dose may be increased to 150mg once daily. If needed, the dose can be further increased up to 225mg once daily. Dose increments should be made at intervals of approximately 2 weeks or more, but not less than 4 days.Usually, the dosage for prevention of relapse or for prevention of recurrence of a new episode is similar to that used during the index episode. Patients should be re-assessed regularly in order to evaluate the benefit of long-term therapy.
The manufacturer of mirtazapine says:
.......***Careful dosing*** as well as regular and close monitoring is necessary in patients with epilepsy and organic brain syndrome. As with other antidepressants, Mirtazapine tablets should be introduced cautiously in patients who have a history of seizures. **Treatment should be discontinued in any patient who develops seizures**, or where there is an increase in seizure frequency. Antidepressants should be avoided in patients with unstable seizure disorders/epilepsy and patients with controlled epilepsy should be carefully monitored.....
Side effects........
Nervous system disorders:
Mania, convulsions (insults), tremor, myoclonus. There have been rare reports of agitation and hallucinations.From the British National Formulary:
..........Combination of two antidepressants can be dangerous and is rarely justified (except under specialist supervision)......
Ed
Posted by jboud24 on November 5, 2004, at 14:20:20
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by ed_uk on November 5, 2004, at 12:55:17
Remeron is not pro-convulsant. Show me a study that says so, but I don't think you'll find one. Here's why Remeron might be beneficial for seizures: via serotonin-2a blockade, dopamine levels are increased in the mPFC region of the brain. Dopamine is a natural anti-convulsant. Additionally Remeron has not been shown to have no effect in vivo on serotonin levels in the any part of the brain. It also, via blockade of alpha-2 adrenergic receptors increases DA further and NE in the mPFC region of the brain.
Effexor on the other hand...Justin
Posted by crazychickuk on November 5, 2004, at 14:51:08
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by jboud24 on November 5, 2004, at 14:20:20
I am so sorry to hear that.... I hope you get some justice done..
My thoughts are with you ((hugs))
Posted by bethesdabob on November 5, 2004, at 15:34:45
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by bethesdabob on November 5, 2004, at 11:11:41
Appreciate your kind words and information.
Attorneys don't say much, mostly don't call us we'll call you when we know something, in this state malpractice/negligence papers must be filed within two years of death or injury, have read just about everything on Google I can about her mixture the past 11 months, get pretty upset when I read stuff like what Ed provided, I'm just a layman, what are doctors thinking when they put people on these mixtures ?
Guess if I could say or do anything it would be to caution you about the potential for harm as well as good that medicines provide.
God bless you all.
Posted by crazychickuk on November 5, 2004, at 18:59:22
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by bethesdabob on November 5, 2004, at 15:34:45
Well i am actually never gonna take another medication for mental things again.. because in my experience they just worsen things... i am gonna let my brain adjust back to normal it was onece normal and it will be again one day...
Do let us all know even if its a few yrs or wat eva post back let us know, hope all goes well for you..you take care of your family and yourself.... let the atternys take care of the malpractice/negligence ...
hugs to you all..
Posted by ed_uk on November 5, 2004, at 19:26:14
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by crazychickuk on November 5, 2004, at 18:59:22
Hello Justin.......
I never said that mirtazapine had been proven to be proconvulsant, just that convulsions have been reported as a (possible) side effect. Similarly, seizures have been reported to occur in patients treated with mianserin, mirtazapine's close chemical cousin. As a result, it may be unwise to administer a high dose of mirtazapine to someone who was known to be epileptic, particularly in combination with an exceptionally high dose of venlafaxine- a drug which has been associated with convulsions both at therapeutic doses and in overdose. Your post suggests that mirtazapine is an well established anticonvulsant, but this is not the case.
All the best........
Ed
Posted by jboud24 on November 6, 2004, at 6:52:06
In reply to Is Remeron proconvulsant?, posted by ed_uk on November 5, 2004, at 19:26:14
No ed, I said Remeron is NOT a convulsant/seizure-inducing medicine. Re-read my post.
Justin
Posted by ed_uk on November 6, 2004, at 15:40:52
In reply to Re: Proconvulsant - Effexor with Remeron ???, posted by jboud24 on November 5, 2004, at 14:20:20
Hello again Justin.....
You said: 'Here's why Remeron might be beneficial for seizures', suggesting that it may have anticonvulsant properties. As you said, it is possible that Remeron could be beneficial for some patients with seizures, but this does not rule out the possibility that other patients may experience convulsions as an adverse effect. After all, other antidepressants such as isocarboxazid (Marplan) have been reported to have a variable effect on seizure frequency- increasing the frequency of seizures in some patients while decreasing the frequency in others.
Since mirtazapine is a potent histamine H1 antagonist, it might be expected to induce seizures in certain susceptible individuals. Clearly, even if Remeron does have the potential to be proconvulsant, it is an extremely weak proconvulsant, perhaps because of the reasons you outlined. Although seizures are only very rarely reported in patients treated with Remeron, seizures have been reported both in epileptic patients as well as in patients without a history of seizures. Some of the people were receiving other drugs at the same time, but others were not. This doesn't prove anything, but is a cause for concern- hence the warning provided by Organon.
We cannot ignore the possibility that Remeron may be responsible for the induction of seizures in rare cases.
The potential role of other H1 antagonists in the induction of seizures had been examined numerous times. Unfortunately, since may antihistamines have various other pharmacological actions as well as H1 antagonism, the role of the H1 receptor can be difficult to study.Here in an interesting abstract from an article, i've highlighted the bits which i felt were most relevent....
Prog Neurobiol. 1997 Jun;52(2):145-57. Related Articles, Links
Role of the central histaminergic neuronal system in the CNS toxicity of the first generation H1-antagonists.Sangalli BC.
Hudson Valley Regional Poison Control Center, Phelps Memorial Hospital Center, North Tarrvtown, New York 10951, USA.
First-generation H1-antagonist-induced central toxicity often includes psychiatric changes, seizures and hallucinations, commonly thought to result from their central anticholinergic effects. Interference with the central functions of histamine have not been adequately addressed, despite the identification of histamine as a central neurotransmitter and neuromodulator. **A synthesis of data support antagonism of H1-receptors as critical to the CNS toxicity of these drugs.** The histaminergic neuronal system (HNS) is involved in a variety of global brain functions. Inherent or induced alterations in the HNS are associated with behavioral disorders. **Clinical and experimental evidence support a role for the HNS in seizure protection and a relationship exits between histamine regulated systems and seizures. Histamine has important neuromodulatory influences on the central electrophysiology which underlies normal thalamocortical function. H1-antagonists block the H1-receptor-mediated reduction of a background-leakage K+ current (IKL) in central neurons. Secondary alterations in other ionic currents and alterations in synaptic responses to glutamate and GABA are produced. The non-H1 receptor-mediated effects of histamine persist in the presence of these drugs, contributing to imbalances in central electrophysiology. H1-antagonist-induced changes are similar to the electrical disturbances thought to underly epileptic seizures** and may adequately explain their hallucinogenic activity. These data form the basis for this review and must be considered as a major mechanism for the CNS toxicity of the first-generation H1-antagonists.
I'm glad we both agree on venlafaxine!!
All the best.....
Ed.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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