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.
poster:ed_uk
thread:411248
URL: http://www.dr-bob.org/babble/20041103/msgs/412619.html