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
poster:ed_uk
thread:411248
URL: http://www.dr-bob.org/babble/20041103/msgs/412178.html