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Remeron: Good informative Article


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Mirtazapine (Remeron): A Newer Antidepressant  1999

 

PETER M. HARTMANN, M.D., York Health System, York, Pennsylvania

 

Mirtazapine is a newer antidepressant that exhibits both noradrenergic and serotonergic activity. It is at least as effective as the older antidepressants for treating mild to severe depression. Sedation is the most common side effect. Although agranulocytosis is the most serious side effect, it is rare (approximately one in 1,000) and usually reversible when the medication is stopped. Mirtazapine is relatively safe in overdose. Many clinicians consider mirtazapine a second-line or even third-line antidepressant, to be used when older antidepressants are not tolerated or are ineffective. Physicians who are concerned about the risks of elevated lipid levels and agranulocytosis may choose to reserve mirtazapine as a third-line choice. It is particularly useful in patients who experience sexual side effects from other antidepressants. Mirtazapine is also a good choice in depressed patients with significant anxiety or insomnia. Although mirtazapine has been used successfully in Europe for a number of years, its place in the care of patients with depression in the United States has not yet been established.

 

Antidepressants remain the cornerstone of treatment of depression by primary care physicians.1,2 As new antidepressants are introduced to the market, physicians need to determine their place. Table 1 compares selected antidepressants in terms of dosages and costs. A recent antidepressant introduced to the U.S. market is mirtazapine (Remeron).

 

 

TABLE 1

Comparison of Selected Antidepressants

Antidepressant

Daily dosage range

Cost*

Bupropion (Wellbutrin) 300 to 400 mg $75 to 100

Fluoxetine (Prozac) 20 to 80 mg 75 to 290

Mirtazapine (Remeron) 15 to 30 mg 59 to 61

Nefazadone (Serzone) 200 to 600 mg 29 to 87

Paroxetine (Paxil) 10 to 40 mg 60 to 67

Sertraline (Zoloft) 50 to 200 mg 65 to 132

*--Estimated cost to the pharmacist based on average wholesale prices, for one month's therapy at the lowest usual dosage level, in Red book. Montvale, N.J.: Medical Economics Data, 1998. Cost to the patient will be higher, depending on prescription filling fee.

 

As with any new drug, mirtazapine's place in the treatment of depression is not yet clear. Selective serotonin reuptake inhibitors (SSRIs) have become the drugs of choice in the treatment of depression.3 Generally, either the older tricyclic antidepressants or the newer antidepressants are used for second-line therapy.4 During the first few years of introduction to the U.S. market, it is reasonable for an antidepressant such as mirtazapine to be reserved for use in patients who do not tolerate or do not respond to initial therapy with SSRIs.

 

Pharmacology

 

Mirtazapine is a tetracyclic piperazino-azepine, which has a different structure from any other currently used antidepressant. It enhances central noradrenergic and serotonergic activity by blocking alpha2 receptors and selectively antagonizing 5HT2 and 5HT3 receptors.5-7 Thus, it is being classified as a noradrenergic and specific serotonergic antidepressant and referred to as an NaSSA.8-10

 

Mirtazapine is well absorbed without regard to food intake. It demonstrates linear kinetics over its usual dosage range and reaches peak plasma level approximately two hours after an oral dose.11 The elimination half-life is 20 to 40 hours, so a steady state is reached in approximately five days. Mirtazapine is metabolized in the liver via the P450 cytochrome oxidase pathway, inhibiting cytochromes 2D6, 1A2 and 3A4. It is excreted in the urine. Clearance of the drug is diminished in the presence of liver or renal impairment. Therefore, a lower dosage is recommended in elderly patients and those with liver or renal dysfunction.

 

Mirtazapine is currently approved for use in adults. Because it is unknown if mirtazapine is secreted in breast milk, it should be used with caution in breast-feeding mothers. The U.S. Food and Drug Administration has labeled mirtazapine as a pregnancy category C drug.12

 

Efficacy

 

 

The most serious side effect of mirtazapine treatment, although rare, is agranulocytosis.

 

In the treatment of depression, as measured by Hamilton Depression rating scales, mirtazapine is clearly superior to placebo.13-15 Several studies have shown mirtazapine to be at least as effective as amitriptyline (Elavil), trazodone (Desyrel) and fluoxetine (Prozac).11,16,17 Mirtazapine has been used successfully in the treatment of mild to severe depression.18

 

Mirtazapine is especially helpful in patients with depression who are anxious; this drug has been shown to reduce anxiety and has even been used to relieve preoperative anxiety and insomnia in patients having gynecologic surgery.13,19,20 Depressed patients with insomnia generally experience significant improvement while taking mirtazapine, including decreased sleep-onset latency, deeper sleep and fewer awakenings.5,20 As with other antidepressants, mirtazapine has a delayed onset--although antidepressant effects may be noticeable after just one week.11,14,18

 

Side Effects

 

The most common side effects of mirtazapine are dose-dependent drowsiness (54 percent), dry mouth (25 percent), increased appetite (17 percent), weight gain (12 percent) and dizziness (7 percent). These side effects tend to improve with time.3,7,12,18 Mild to moderate elevations in cholesterol, triglyceride and alanine aminotransferase (ALT: formerly known as SGPT) levels may also occur. The most serious side effect is agranulocytosis, which occurs in approximately one in 1,000 patients. This incidence is no higher than the incidence of other antidepressants. To date, all patients with this complication have recovered completely when the medication was stopped.21 Routine laboratory monitoring is not recommended. A complete blood count and ALT measurement may be obtained if symptoms or signs suggest a need.

 

Mirtazapine has few, if any, cardiac effects and causes very little orthostatic hypotension.3,21-23 Unlike the SSRIs, mirtazapine is associated with a very low incidence of sexual dysfunction, so it may be a good choice for use in patients who have experienced this side effect with other antidepressants.9,10,24

 

Information about overdose of mirtazapine in suicide attempts is limited because the drug is so new. However, to date no deaths have been recorded, and seizures and cardiotoxicity have not been noted in case reports. Excessive sedation appears to be the main effect of an overdose of mirtazapine.18,21

 

Drug-Drug Interactions

 

 

Mirtazapine should be reserved for use in patients who have not responded to first-line treatment or in selected patients with severe anxiety or insomnia.

 

Multiple hepatic pathways are used in the metabolism of mirtazapine, so clinically significant drug-drug interactions are unlikely to occur.3,25 However, little is actually known about drug-drug interactions in the clinical setting.25 Because of its sedative effects, alcohol should not be taken with mirtazapine and excessive sedation may result when it is used with other sedating drugs, such as benzodiazepines.3,26 Mirtazapine should not be used within 14 days of the use of a monoamine oxidase inhibitor because of the possibility that a hypertensive crisis will be triggered.12

 

Dosage

 

The usual starting dosage is 15 mg, with a usual dosage range of 15 to 30 mg per day.18 Because of its common sedative effect, it is usually recommended that mirtazapine be taken at bedtime. It is available in 15-mg and 30-mg scored tablets.

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Thanks Lee for posting this.  As you can probably tell I have developed an interest in this medication since starting to discuss it recently lol!

 

One thing I remember that's a bit different to the article is that the drug is structurally almost identical to the older AD mianserin (Tolvon and other brand names).  Both are tetracyclics and both were (from memory) originally introduced to the market by Organon; I think mirtazapine is called "aza-mianserin".  Mianserin is said to have very similar effects on brain receptors although unlike mirtazapine it also inhibits norepinephrine reuptake.

 

I took mianserin years ago and did find a beneficial effect on my depression, mainly a norepinephrine-like energy boost after a few days on it.  I'm not sure if mirtazapine would have as much norepinephrine action.

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Thanks Lee for posting this.  As you can probably tell I have developed an interest in this medication since starting to discuss it recently lol!

 

One thing I remember that's a bit different to the article is that the drug is structurally almost identical to the older AD mianserin (Tolvon and other brand names).  Both are tetracyclics and both were (from memory) originally introduced to the market by Organon; I think mirtazapine is called "aza-mianserin".  Mianserin is said to have very similar effects on brain receptors although unlike mirtazapine it also inhibits norepinephrine reuptake.

 

I took mianserin years ago and did find a beneficial effect on my depression, mainly a norepinephrine-like energy boost after a few days on it.  I'm not sure if mirtazapine would have as much norepinephrine action.

 

They say in lower doses it works on seratonin, from 0-15mg...and from 15-45mg it works on norepinephrine. Thats why my doc rx'ed me for anxiety in a low dosage. Just what I heard..

Lee

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Hi Lee,

  I've been taking 15mg. Remeron for sleep and depression for years. I tried almost all the other a/d out there, but this one has worked great for me. It helps me alot. Thank you for the article.

  Isaiah 26:3... You will keep him in perfect peace whose mind is stayed on You, because he trusts in You.

 

Blessings,

Rhapsodygirl

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They say in lower doses it works on seratonin, from 0-15mg...and from 15-45mg it works on norepinephrine. Thats why my doc rx'ed me for anxiety in a low dosage. Just what I heard..

Lee

 

I'd be interested in hearing how this goes for you, and whether it does have the serotonin action at lower doses.  Mianserin had a sedating action even at low starting dosage but I regarded that as being the anti-histamine side effect since it went away after 2-3 days.  I'm still very wary of taking any antidepressants but am leaning heavily towards this one if I do try anything, especially if it is able to have a continuing sleep effect.

 

Could you please say how it works out, including whether it has a sustained sleep-enhancing effect?

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Hi Lee,

  I have always stayed at 15mg. every night. I once tried taking 30mg. and boy did I have a rough night. Weird dreams and woke up really groggy. I stay on it because it does help me sleep, and with the cfs/ebv come bouts of depression. Having a chronic illness really causes you to know your limitations, and comes with it's challenges. None the less, this is where the Lord has me, and at times I do get discouraged. Yet, I do thank and praise him for giving me a new heart and carrying me through all my trials.

  I tried almost every antidepressant out there. After my first chemo I had to go on someting. Panic attacks, severe depression. Remeron was the only one that worked. I will stay on it most likely until I go be with the Lord.

  I hope I have helped you in some way. Thank goodness Jesus is ALWAYS with us!! Keep in touch :)

 

Blessings,

rhapsodygirl

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  • 2 weeks later...

Hi Lee,

  I have always stayed at 15mg. every night. I once tried taking 30mg. and boy did I have a rough night. Weird dreams and woke up really groggy. I stay on it because it does help me sleep, and with the cfs/ebv come bouts of depression. Having a chronic illness really causes you to know your limitations, and comes with it's challenges. None the less, this is where the Lord has me, and at times I do get discouraged. Yet, I do thank and praise him for giving me a new heart and carrying me through all my trials.

  I tried almost every antidepressant out there. After my first chemo I had to go on someting. Panic attacks, severe depression. Remeron was the only one that worked. I will stay on it most likely until I go be with the Lord.

  I hope I have helped you in some way. Thank goodness Jesus is ALWAYS with us!! Keep in touch :)

 

Blessings,

rhapsodygirl

 

Hi There....

You last message was really encouraging to me...Thanks.

Here is an UPDATE.

Been titrating up from 3.75mg Remeron to almost 15mg for 23 days.(I am a sissy when it comes to drugs)

Anyway, at almost 15 mg...way to dizzy...I had to go back town to around 10/11mg at night.

Maybe because I am taking .5mg ativan with it???

I want to cross over to V, but trying to find a DR who will write script. Mine Wont!  Dork!

Anyway, Remeron is pretty good....

It took away rumerating thoughts in the first few days...lessened anxiety.

I slept like 13 hrs the 1st day.

It is great for sleep so far.    Vivid dreams.

I a little groggy/sleepy some days...

I will have to see if that goes away. If not I may discontinue.

Once I get off the benzos, we will see.

Today is day 22 or 23 of Remeron.

There were a few of you that wanted to know...I would say, try it. Everyone is so different.

At low doses it is great for sleep. They say at higher doses, it energizes (around 30 mg???) see my article above.

Anyway, Thanks for your prayers.

 

I am still at .5mg ativan at night.

When I try to decrease, I get anxiety and sleeplessness...

I want to CO to valium....

 

Lee out West.

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