Mirtazapine Amitriptyline

Mirtazapine has been investigated in long-term treatment, and interestingly, although both amitriptyline, the comparator, and mirtazapine were effective, mirtazapine was associated with fewer relapses than was amitriptyline [S. A. Montgomery 1996). 

Smith WT, Glaudin V, Panagides J, et al Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull 26 191-196, 1990... 

The approval of mirtazapine in the United States was based on six double-blind, placebo- and amitriptyline-controlled studies in which it was found to be superior to placebo and comparable with amitriptyline in terms of antidepressant efficacy (173,174). In a double-blind, crossover study, 63% of patients who failed to respond to 6 weeks of double-blind treatment with amitriptyline responded to mirtazapine (175). In two studies, mirtazapine was found to be efficacious in the treatment of patients hospitalized for major depression. In the first study, the antidepressant efficacy of mirtazapine was comparable with that of amitriptyline and superior to placebo (176). In the other study, the antidepressant efficacy was superior to that of fluoxetine (118). There are advantages and disadvantages to mirtazapine, including the following ... 

A double-blind continuation study has been conducted with mirtazapine. As with venlafaxine and nefazodone, patients in this acute, double-blind, placebo- and active-controlled study with mirtazapine could remain on the double-blind treatment at the end of the initial 6-week efficacy trial and were then followed up for up to 1 year. There was a statistically significant lower risk of relapse (defined as HDRS > 16) on both mirtazapine (18%) and amitriptyline (28%) in comparison with placebo (53%), indicating that mirtazapine has maintenance efficacy (274). More recently, a 40-week, double-blind, placebo-controlled crossover study was performed with mirtazapine (275). Patients maintained on this drug had less than half the likelihood of relapsing than those patients switched to placebo (i.e., 19.7% versus 43.8%, p <0.01). 

Zivkov M, Roes KCB, Pols AB. Efficacy of Org 3770 (mirtazapine) vs. amitriptyline in patients with major depressive disorder a meta-analysis. Hum Psychopharmacol 1995 10 S135-S145. 

Catterson M, Preskorn SH. Double-blind crossover study of mirtazapine, amitriptyline, and placebo in patients with major depression. In New Research Program and Abstracts of the 149th annual meeting of the American Psychiatric Association, New York, May 6, 1996 NR157. 

The other tertiary TCA that has dual serotonergic-noradrenergic effects, amitriptyline, like imipramine, appears to be consistently effective in anxiety disorders. Newer antidepressants such as mirtazapine, nefazodone, paroxetine, and venlafaxine may also benefit patients with anxiety disorder ( 60, 61, 62 and 63). 

OFFICIAL NAMES Amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), imipramine (Norfranil, Tofranil), isocarboxazid (Marplan), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil), phenelzine (Nardil), protriptyline (Vivactil), sertraline (Zoloft), thioridazine (Mellaril), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Sur-montil), venlafaxine (Effexor) the herb St. John s wort (Hypericum perforatum) is sold over-the-counter without prescription STREET NAMES Happy pills... 

Tricyclics and the second- and third-generation agents differ mainly in the degree of sedation they produce (greatest with amitriptyline, doxepin, trazodone, and mirtazapine) and their antimuscarinic effects (greatest with amitriptyline and doxepin Table 30-3). SSRIs are generally free of sedative effects and remarkably safe in overdose. Combined with the ease of once-a-day dosing, these qualities may explain why they have become the most widely prescribed antidepressants. 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

Trimipramine is a sedating tricyclic antidepressant that has been used as a hypnotic (1) it shares this activity with other drugs of its class, notably amitriptyline, dosulepin, doxepin, and trazodone, and with the tetracyclics mianserin and mirtazapine. Trimipramine may be preferred for this purpose, since it has less effect on sleep architecture, including REM sleep (2), and has only a modest propensity to produce rebound insomnia in a subset of patients (3). Sedative antidepressants may be particularly appropriate for individuals at risk of benzodiazepine abuse and patients with chronic pain (4). The usual pattern of tricyclic adverse effects, especially antimuscarinic and hypotensive effects and weight gain, can be expected. Some authors, enthusiastic about GABA enhancers, contend that antidepressants are not useful hypnotic alternatives (5). 

In major depression, the efficacy of mirtazapine is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, and venlafaxine. 

DA agonists levodopa, bromocriptine, ropinirole, pramipexole, selegiline AAAD inhibitor carbidopa M-blockers benztropine, trihexiphenidyl MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone... 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

V. Drug or laboratory interactions. There is some evidence that milk thistle may inhibit CYP2C9 and CYP3A4 enzyme activity, which might theoretically increase plasma levels of dmgs metabolized by these enzymes, including amitriptyline, diazepam, clozapine, warfarin, mirtazapine, ketoconazole, and others. Drug interactions with milk thistle extract have not been reported in humans. 

No pharmacokinetic interaction normally occurs between risperidone and amitriptyline or mirtazapine, but extrapyramidal reactions have been reported in one patient taking amitriptyline with risperidone. 

The tricyclic antidepressants, clomipramine, desipramine and imipramine, reduce or abolish the antihypertensive effects of clonidine. Other tricyclics are expected to behave similarly. A hypertensive crisis developed in a woman taking clonidine who was also given imipramine, and severe pain ocenrred in a man taking amitriptyline and diamorphine when he was given intrathecal clonidine. Conversely, the tetracyclics, maprotiline and mianserin do not appear to alter the antihypertensive effects of clonidine. An isolated case report describes a hypertensive crisis in a patient taking mirtazapine and clonidine. Hypotension ocenrred in a boy taking clonidine and trazodone. 

The manufacturers siay that two weeks should elapse between taking an MAOI and mirtazapine. Mirtazapine combined with other serotonergic antidepressants may possibly increase the risk of bleeding and/or the serotonin syndrome. SSRIs may increase plasma levels of mirtazapine and there is a report of hypomania associated with combined use. The concurrent use of mirtazapine with amitriptyline may have a minor effect on the levels of both drugs. 

In a single-blind, crossover study involving 24 healthy subjects, mirtazapine 15 to 30 mg daily, amitriptyline 25 to 75 mg daily or both drugs were given for periods of 9 days and in addition, 8 subjects received placebo. Amitriptyline increased the maximum plasma levels of mirtazapine, in male subjects only, by 36%. Mirtazapine increased the maximum... 

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