Questions and answers

✍ Scribed by Milana Zivkov

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 44 KB
• Volume: 7
• Category: Article
• ISSN: 1091-4269
• DOI: 10.1002/(sici)1520-6394(1998)7:1+<33::aid-da8>3.0.co;2-g

✦ Synopsis

course globally elevating dopamine runs the risk of making people psychotic, but there may be evidence that hitting noradrenaline early in treatment may accelerate response.

I.M. Anderson: It is important not to forget pharmacokinetic issues in considering onset of action. Meta-analyses of all the direct comparative studies of the SSRIs suggests that fluoxetine, which has a longer half-life, comes out slower.

Charles B. Nemeroff: The antibiotic and cardiac literature teaches us that there is a relationship between half-life and the time it takes to attain steady state, but I don't think there are any data available about that, or, for example, that nefazodone, which has the shortest halflife, acts any faster than fluoxetine.

Q: What effect does mirtazapine have on sleep? Roger Pinder: There are good data in animal and healthy volunteers and ongoing work in depressed patients, all of which suggest that mirtazapine improves deep slow wave sleep stages 3 and 4 by 5-HT 2 antagonism and this effect lasts throughout treatment. Antihistamine effects in the first few days might also contribute to getting patients to sleep and keeping them asleep, but that is a very transient effect.

Nutt:

The key EEG findings are a REM advance and reduced slow wave sleep. Certainly drugs which increase slow wave sleep will be rectifying the slow wave sleep deficit in depression. So there is an obvious benefit for a drug like mirtazapine, with a 5-HT 2 blockade improving or rectifying the slow wave deficit in sleep.

Q: What effect does mirtazapine have on other serotonin receptors?

Pinder: Aside from 5-HT 1 , 5-HT 2, and 5-HT 3, the only serotonin receptors which I regard as relevant to the central nervous system at the moment are 5-HT 6 and 5-HT 7 which may be involved in schizophrenia and depression. It looks as though mirtazapine's antagonism of 5-HT 2 and 5-HT 3 may extend to these receptors as well.

Q: Can you combine mirtazapine with sumatriptan, the 5HT 1D agonist?

Pinder: There are no direct data on this combination, but on the basis of mirtazapine's effect on the cytochrome P 450 system, you would not expect a pharmacokinetic interaction. From pharmacological principles, combining sumatriptan's 5-HT 1D agonism with mirtazapine, which is an indirect 5-HT 1A agonist and a