Letters to the Editor

Clinical Pharmacology of Mirtazapine: Revisited


Am Fam Physician. 1999 Sep 15;60(4):1101.

to the editor: We would like to respond to the recent article by Dr. Hartmann titled, “Mirtazapine: A Newer Antidepressant.”1 We have conducted independent meta-analyses with mirtazapine that have established its efficacy in the treatment of depression.2,3 In addition, Fawcett and colleagues2 reported significant improvement in symptoms of anxiet/gitation or anxiet/omatization beginning with week 1, which was comparable to improvement with the use of amitriptyline during the treatment period. Moreover, clinical experience with mirtazapine continues to demonstrate lack of sexual dysfunction as a side effect.4

Dr. Hartmann also indicated that agranulocytosis occurs in approximately one in 1,000 patients who are treated with mirtazapine,1 which is no higher than the incidence of agranulocytosis with the use of other antidepressant agents. To be more precise, postmarketing surveillance reports have demonstrated that agranulocytosis is rarely associated with use of mirtazapine. Only six cases of agranulocytosis in approximately 2 million exposures have been reported worldwide (Organon, Inc., unpublished data, 1999).

In all of these cases, at least one concomitant medication that was associated with this adverse effect had been administered an/r the patients had a disease that was related to this adverse effect. Furthermore, all six of the patients recovered. This incidence of agranulocytosis is the same as the expected incidence in the general population, which suggests that the association between mirtazapine and agranulocytosis may be coincidental.

In vitro data have shown that mirtazapine is a weak inhibitor of CYP1A2, CYP2D6 and CYP3A45; therefore, significant clinical interactions are unlikely.5 Mirtazapine augmentation has shown minimal drug interaction effects when used with fluoxetine, venlafaxine, sertraline, paroxetine or desipramine as an augmenting agent in the treatment of refractory depression.6 In addition, mirtazapine (at 10 to 30 times the maximum recommended daily dosage) has recently been shown in a small number of patients to be safe, including patients concomitantly receiving benzodiazepines.7

We believe that mirtazapine is useful in the treatment of depression, especially in patients who have concomitant symptoms of insomnia, anxiety, agitation or sexual dysfunction.


show all references

1. Hartmann PM. Mirtazapine: a newer antidepressant. Am Fam Physician. 1999;59:159–61....

2. Fawcett J, Barkin RL. A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry. 1998;59:123–7.

3. Davis JM. Is mirtazapine a better antidepressant than SSRIs? Essential Psychopharmacol. 1998;2:309–30.

4. Hirschfeld RM. Sexual dysfunction in depression: disease- or drug-related? Depress Anxiety. 1998;7(Suppl 1):21–3.

5. Stimmel GL, Sussman N, Wingard P. Mirtazapine safety and tolerability: Analysis of the clinical trials database. Prim Psychiatry. 1997;1:82–96.

6. Carpenter LL, Jocic Z, Hall JM, Rasmussen SA, Price LH. Mirtazapine augmentation in the treatment of refractory depression. J Clin Psychiatry. 1999;60:45–9.

7. Bremner JD, Wingard P, Walshe TA. Safety of mirtazapine in overdose. J Clin Psychiatry. 1998;59:233–5.

EDITOR'S NOTE: This letter was sent to the author of “Mirtazapine: A Newer Antidepressant,” who declined to reply.


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This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.



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