I know a lot of people here are on antidepressants for anxiety/depression/FB/FF/HH but get sexual dysfunction or find it ineffective. There is a newer antidepressant called Mirtazapine which works on the same primary receptor (alpha2-adrenergic autoreceptor) as clonidine however paradoxically as an antagonist (the theory that there is an alpha2 dysregulation not simply an excess or deficiency). It recently has been shown to help hot flushes like clonidine was many years ago. It also increases serotonin similar to SSRIs, Prozac, Paxil etc with significantly less risk of sexual dysfunction but can cause some more rapid weight gain in some (thought through an increase in appetite more than metabolism) & sedation so best taken around bedtime. Clonidine (the alpha2-agonist) also can exacerbate depression in some as mentioned in the CME article & links at this site and should not be used at the same time as mirtazapine. Some who have trouble finding a doctor to prescribe clonidine may find it easier to get a prescription for this antidepressant. It also is supposed to have a faster onset of action than SSRIs/older ADs and side effects often improve with the higher doses. Below is a recent abstract & if anyone decides to try it with their MD's guidance, report back.  For pain here.

Treatment of hot flushes with mirtazapine: four case reports [In Process Citation]

 * New Article - Maturitas 2000 Oct 31;36(3):165-8    (ISSN: 0378-5122)

Waldinger MD; Berendsen HH; Schweitzer DH
Department of Psychiatry and Neurosexology, Leyenburg Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands.

Objective: To evaluate the effect of mirtazapine on the severity of hot flushes and bouts of perspiration in women. Method: In two women with depression a reduction in hot flushes was noticed by serendipity during treatment with mirtazapine 15-30 mg/daily. On the basis of this observation clinical studies were extended with two non-depressed and non-anxious women with hot flushes. Both subjects were prescribed mirtazapine daily. Results: Four cases are described as case reports. All subjects reported a practically complete disappearance of hot flushes and associated perspiration, within the first week of treatment. Conclusion: Mirtazapine appears to have a substantial ameliorating effect on hot flushes and perspiration bouts. It is postulated that the 5-HT(2A) blocking properties of mirtazapine is accounted in the symptomatic relief of hot flushes. In addition it is hypothesized that the serotonergic system is crucially involved in the pathogenesis of hot flushes and perspiration bouts. Further evaluation in double-blind placebo-controlled studies is encouraged.

Language: English
MEDLINE Indexing Date: 200011
Publication Type: MEDLINE RECORD IN PROCESS
Publication Type: JOURNAL ARTICLE
PreMedline Identifier: 0011063897
Unique NLM Identifier: 20519842

Here's an interesting article that tries to explain the interaction of hormones & neurotransmitters. Much of what is known about flushing is from studying menopausal hot flushes. From clonidine to antidepressants:

http://www.science.com.br/henrys_corner/artigos_tecnicos/the_role_of_serotonin_in_hot_flushes.pdf *

If down: http://www.angelfire.com/journal2/sadhelp/shf.pdf
(* Requires Adobe Acrobat since in .pdf format - Free Acrobat readers at http://www.acrobat.com )

My initial impression of the article is that while I can appreciate the scope of it, I feel their 5HT2A hypothesis is oversimplistic. If it were that simple then nefazodone/Serzone would likely have popped up as promptly effective for hot flushes already. It is considered a decent antidepressant at the right dose but not very effective for panic or anxiety but does not generally cause sexual dysfunction or weight gain so it may be worth a trial. Serzone unfortunately interacts with a lot of meds like Xanax so that should be looked at prior.

Remeron/mirtazapine has had some positive reports in the literature & mixed reviews anecdotally from rosacea flushers, some respond well while others don't at all. This may be because it blocks 5HT2, & 5HT3-like ondansetron/Zofran (reported effective anecdotally for erythematous rosacea & ocular rosacea) as well as histamine; what could be negating benefit is that it is primarily an Alpha2NE-Antagonist (opposite of clonidine -used for hot flushes & anxiety). Interactions have been noted for mirtazapine & clonidine. If it works well it could also be normalizing a dysfunctional alpha2 autoreceptor.  Also some selective alpha2NE-antagonists have been shown to be anxiolytic (anti-anxiety) while less specific antagonists are not:

Life Sci 1994;54(10):PL179-PL184 Related Articles, Books

The alpha-2 antagonists idazoxan and rauwolscine but not yohimbine or piperoxan are anxiolytic in the Vogel lick-shock conflict paradigm following intravenous administration.

La Marca S, Dunn RW.

Anaquest, Inc., Murray Hill, NJ 07974.

The alpha 2 agonist clonidine has been shown to be anxiolytic in a number of preclinical anxiety models. Interestingly, intravenous infusion of the alpha 2 antagonists idazoxan at 10 mg/kg and rauwolscine at 2.24 mg/kg significantly disinhibited lick-shock conflict responding in rats similar to the alpha 2 agonist clonidine (0.022 mg/kg) and the benzodiazepine diazepam (0.5 mg/kg). However, the alpha 2 antagonists yohimbine and piperoxan, the alpha 2 agonists medetomidine, guanfacine, and guanabenz, the non-specific alpha antagonist phentolamine, and the alpha 1 antagonist prazosin did not disinhibit conflict responding in the Vogel lick-shock paradigm. In fact, yohimbine has been shown to be anxiogenic in both animals and man. This may be due to yohimbine's lack of specificity and its ability to inhibit GABAergic release. In addition, all of these agents, except idazoxan, did not increase water consumption in water deprived rats. Idazoxan (10 mg/kg) significantly decreased water consumption by 45%. Therefore, idazoxan increased conflict responding for water reward at a dose (10 mg/kg) which also decreased water consumption in a non-conflict paradigm. These data suggest that agents with selective antagonism at the alpha 2 receptor site may be anxiolytic while agents with less specificity at this site such as yohimbine, piperoxan, and phentolamine are not anxiolytic.

PMID: 7906377 [PubMed - indexed for MEDLINE]

Since mirtazapine blocks clonidine it is likely not very selective however (yet still has reported anxiolytic effects):

Abo-Zena RA, Bobek MB, Dweik RA. Related Articles
Hypertensive urgency induced by an interaction of mirtazapine and clonidine.
Pharmacotherapy. 2000 Apr;20(4):476-8.
PMID: 10772378 [PubMed - indexed for MEDLINE]
 
Bengtsson HJ, Kele J, Johansson J, Hjorth S. Related Articles
Interaction of the antidepressant mirtazapine with alpha2-adrenoceptors modulating the release of 5-HT in different rat brain regions in vivo.
Naunyn Schmiedebergs Arch Pharmacol. 2000 Nov;362(4-5):406-12.
PMID: 11111835 [PubMed - indexed for MEDLINE]

We are still learning about neurotransmitters, their subtypes, interaction with other neurotransmitter systems & how psychotropics work. Remeron is considered effective for serious depression & again mixed reviews for anxiety with low incidence of sexual dysfunction commonly associated with SSRIs but more commonly causes increased hunger/weight gain.

What is Remeron®?

(or REMERGIL, REXER, PROMYRTIL AS IT IS CALLED IN OTHER COUNTRIES, PLEASE FIND A LIST AT THE END OF THIS SECTION)

Remeron® is the tradename of Organon's new antidepressant mirtazapine.

Remeron® is the first NaSSA - a Noradrenergic and Specific Serotonergic Antidepressant. It enhances the release of the neurotransmitter noradrenaline in certain areas in the brain. It also increases the release of another neurotransmitter, serotonin. Such dual action is increasingly being recognised as beneficial for effectiveness in treating depression.

Remeron® is not associated with anticholinergic side effects like constipation, urinary retention and dizziness. In addition, Remeron's action on the serotonergic system is highly specific: it allows the extra serotonin to act on the serotonin receptor site which mediates the antidepressant activity, and it blocks other serotonin receptors which cause the unwanted serotonergic side effects like sexual dysfunction, insomnia, anxiety, agitation, and gastrointestinal disorders like nausea.

The most common side effects of Remeron® are daytime sleepiness which usually subsides rapidly after the first week and in some cases increased appetite and weight gain in some cases.

It is advised to take your daily dose of Remeron at night before going to bed. Of course, you should discuss use of Remeron® and any other questions you may have about Remeron or depression with your doctor.

Where is Remeron® available ?

Remeron is available in following countries.

Country Trade name
Argentina Remeron®
Austria Remeron®
Brazil Remeron®
Chile Promyrtil®
Ecuador Remeron®
Denmark Remeron®
Finland Remeron®
France Norset®
Germany Remergil®
Greece Remeron®
Hong Kong Remeron®
Italy Remeron®
Netherlands Remeron®
Peru Remeron®
Portugal Remeron®
Rep. Ireland Zispin®
Singapore Remeron®
Spain Rexer®
Sweden Remeron®
Turkey Remeron®
United Kingdom Zispin®
USA Remeron®

More info for consumers & medical professionals at:

http://www.remeron.com


>are you saying that Mirtazapine might help FF ?

--->That's what the medline report suggests FF/HH & one may infer FB.

>what do you mean with "It recently has been shown to help hot flushes like CLONIDINE WAS MANY YEARS AGO" ? doesnt it still help flushing ? why did it stop ?

--->Clonidine was shown to help in a study/report like this except this medication (Mirtazapine is the chemical name) also is an antidepressant with anti-anxiety effects. For this reason some docs may be more comfortable prescribing it. The sentence doesn't imply clonidine has suddenly become ineffective:) but clonidine can aggravate depression in some. Of interest they both work on the alpha2-adrenergic autoreceptor. Mirtazapine also increases serotonin however similar to SSRIs without sexual dysfunction & insomnia (sleep is generally improved on this).

>"can cause some weight gain in some (thought through an increase in appetite" thats good... i really need more weight.

--->Some find their appetite increased on mirtazapine & may gain some weight.

>going to my doc the 19/03, and im wondering what to ask for. i got this list with medicines that might work.

--->Must be from outside the US, we would date it 03/19 ;), This antidepressant is said to have a faster onset of action than others. My previous post above lists the countries it is available in. You should NOT take mirtazapine & clonidine at the same time (ask your doc how many days you should be off it-less than a week probably). Atenolol for a big speech or event if still needed should be ok but speak with your doc.

Alpha 2-adrenergic mechanism in menopausal hot flushes.

Obstet Gynecol 1990 Oct;76(4):573-8   (ISSN: 0029-7844)

Freedman RR; Woodward S; Sabharwal SC
Lafayette Clinic, Detroit, Michigan.

It has been hypothesized that hot flushes are triggered within the hypothalamus by alpha 2-adrenergic receptors on noradrenergic neurons. We administered intravenous clonidine (an alpha 2-adrenergic agonist) and yohimbine (an alpha 2-adrenergic antagonist) to nine menopausal women with hot flushes and to an asymptomatic comparison group. Hot flushes were defined objectively by skin conductance responses recorded from the sternum; finger temperature recordings and symptom reports were also evaluated. The subjects were prescreened using ambulatory skin conductance monitoring. A significantly greater number of hot flushes occurred during yohimbine sessions than in corresponding placebo sessions (six versus zero). Clonidine significantly increased the amount of peripheral heating needed to provoke a hot flush (40.6 versus 33.6 minutes) and reduced the number of hot flushes that did occur (two versus eight). No hot flushes occurred in the asymptomatic women. These findings support the role of a central alpha 2-adrenergic mechanism in the initiation of hot flushes.

Major Subject Heading(s) Minor Subject Heading(s) CAS Registry / EC Numbers
  • Climacteric [physiology]
  • Clonidine [diagnostic use]
  • Hypothalamus [physiology]
  • Receptors, Adrenergic, alpha [physiology]
  • Yohimbine [diagnostic use]

     

    •
  • Adult
  • Climacteric [drug effects]
  • Galvanic Skin Response [physiology]
  • Middle Age
  • Receptors, Adrenergic, alpha [drug effects]
  • Skin Temperature [physiology]
  • Time Factors
    •
  • 0 (Receptors, Adrenergic, alpha)
  • 146-48-5 (Yohimbine)
  • 4205-90-7 (Clonidine)
    •


    Indexing Check Tags: Comparative Study; Female; Human; Support, U.S. Gov't, P.H.S.

    Language: English
    MEDLINE Indexing Date: 199101
    Publication Type: CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE
    Grant ID: AG-05233-AG-NIA
    Unique NLM Identifier: 91016082
    Journal Code: A; M

    CLINICAL PHARMACOLOGY OF MIRTAZAPINE

    Pharmacodynamics

    Evidence gathered in preclinical studies suggests that mirtazapine enhances central noradrenergic and serotonergic activity. These studies have shown that mirtazapine acts as an antagonist at central presynaptic a2 adrenergic inhibitory autoreceptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity.

    Mirtazapine is a potent antagonist of 5-HT2 and 5-HT3 receptors. Mirtazapine has no significant affinity for the 5-HT1A and 5-HT1B receptors. Mirtazapine is a potent antagonist of histamine (Hi) receptors, a property that may explain its prominent sedative effects.

    Mirtazapine is a moderate peripheral a1 adrenergic antagonist, a property that may explain the occasional orthostatic hypotension reported in association with its use.

    Mirtazapine is a moderate antagonist at muscarinic receptors, a property that may explain the relatively low incidence of anticholinergic side effects associated with its use

    Pain:

    Brannon GE, Stone KD. Related Articles
    The use of mirtazapine in a patient with chronic pain.
    J Pain Symptom Manage. 1999 Nov;18(5):382-5.
    PMID: 10584463 [PubMed - indexed for MEDLINE]

    Craniofacial flushing pain:

    Nutt D, Law J. Related Articles
    Treatment of cluster headache with mirtazapine.
    Headache. 1999 Sep;39(8):586-7. No abstract available.
    PMID: 11279976 [PubMed - indexed for MEDLINE]
     
    The antidepressant mirtazapine successfully treats refractory cluster headache:
    Researchers from the UK report the case of a 56 year old man who had an 11 year history of cluster headache which had proven refractory to treatment with calcium antagonists, lithium, dexamethasone, prednisolone and sumatriptan. However soon after starting a 6 week course of mirtazapine 30mg daily the patient experienced a rapid reduction in the number and severity of attacks.
    Nutt. D et al. Headache 39: 586-587 Per Inpharma 1999; 1215: 13 (27th Nov).
     
    Lessons From Cluster Headaches:
     
    http://www.emedicine.com/NEURO/topic517.htm -Pathophysiology and Treatment of Migraine and Related Headache here- "Cluster headache is an extremely severe, unilateral, orbital or supraorbital pain associated with ipsilateral facial autonomic symptoms. Pain also may radiate to the back of the neck, suboccipital area, and along the carotid artery. Pain often is boring in nature, lasts from 15 minutes to 4 hours, and typically, patient is awakened in the middle of the night with the headache. Tenderness of the temporal artery, facial flushing, and elevated skin temperature on the ipsilateral side have been reported."
     
    & 
     
    http://www.emedicine.com/NEURO/topic70.htm -Cluster Headache from Neurology/Headache And Pain here- 

    Cluster Headache (CH): Synonyms, Key Words, and Related Terms: Bing-Horton syndrome, histaminic cephalalgia, cluster migraine, paroxysmal nocturnal cephalalgia, red migraine, erythromelalgia of the head, sphenopalatine neuralgia, migrainous neuralgia 

    "The pathophysiology of CH is not understood entirely. Its typical periodicity has been attributed to hypothalamic (particularly suprachiasmatic nuclei) hormonal influences. CH pain is thought to be generated at the level of the pericarotid/cavernous sinus complex. This region receives sympathetic and parasympathetic input from the brain stem, possibly mediating occurrence of autonomic phenomena during an attack. The exact roles in CH of immunologic and vasoregulatory factors, as well as the influence of hypoxemia and hypocapnia, are still controversial...
     
    - The association of prominent autonomic phenomena is a hallmark of CH. Such signs include ipsilateral nasal congestion and rhinorrhea, lacrimation, conjunctival hyperemia, facial diaphoresis, palpebral edema, and complete or partial Horner syndrome (which may persist between attacks). Tachycardia is a frequent finding.
     
     

    Reported Treatments: Abortive: High-flow oxygen; Acute: Ergot alkaloids; Prophylactic agents: intranasal capsaicin, intranasal lidocaine, calcium channel blockers-Verapamil, clonidine, beta-blockers, lithium, baclofen, melatonin, methylergonovine maleate, leuprolide, valproate, topiramate, Mirtazapine; short term steroids. Drug resistance-surgical: Radiofrequency trigeminal rhizotomy.

    The antidepressant mirtazapine successfully treats refractory cluster headache:
    Researchers from the UK report the case of a 56 year old man who had an 11 year history of cluster headache which had proven refractory to treatment with calcium antagonists, lithium, dexamethasone, prednisolone and sumatriptan. However soon after starting a 6 week course of mirtazapine 30mg daily the patient experienced a rapid reduction in the number and severity of attacks.
    Nutt. D et al. Headache 39: 586-587 Per Inpharma 1999; 1215: 13 (27th Nov).


    Warnings: The information above is provided for educational purposes and may not be construed as a medical prescription or as a substitute for the advice of your physicians.