Letters to the Editor
Massive Weight Gain and Hostility Force Mirtazapine Stoppage
Dear Editor:
Mirtazapine is a novel antidepressant with a mechanism that involves
enhancing serotonergic and noradrenergic neurotransmission via blockade
of alpha-2 adrenergic autoreceptors and heteroreceptors. Because
of its unique pharmacologic profile, it is devoid of anticholinergic-,
adrenergic-, and serotonin-related side effects (1). The most frequently
reported side effects are mild and transient sedation and weight
gain (1,2). Others have found it to have substantially better tolerability
than the serotonergic or tricyclic antidepressants (3,4). I report
the case of a patient who stopped mirtazapine after severe and unusual
side effects.
Case Report
Ms KD is a 40-year-old nurse with a long history of unipolar depression
that resulted in several hospitalizations and several antidepressant
trials, including electroconvulsive therapy. During one such episode,
her depression was treated unsuccessfully with adequate trials of
citalopram, venlafaxine, paroxetine, and bupropion. After a washout
period of about 10 days, Ms KD was started on 15 mg of mirtazapine
given at bedtime. After a week, this was increased to 30 mg. She
also took 0.5 mg of lorazepam up to twice daily. She remained depressed,
became irritable, and noticed significant and sudden weight gain.
At lower dosages, mirtazepine acts as an antihistamine and enhances
sertononergic transmission, which favours weight gain (4). Therefore,
the dosage was increased to 45 mg daily to recruit and enhance noradrenergic
release, with the hope of controlling her weight. Over a 6-week
period, she gained more than 40 lb. The weight gain was associated
with swelling of her hands, legs, feet, and eyelids. She became
incapacitated because the swelling prevented grasping and turning
faucets, and she became unable to get in and out of the bathtub.
Climbing stairs became impossible, and she needed help with most
activities. Ms KD also became extremely anxious and very hostile,
especially toward her 2 children. She became fearful at night and
asked her husband to be close to her, preventing him from watching
television. All these new problems—and especially her hatred
of her own children—frightened her, and she requested that
mirtazapine be discontinued. Shortly thereafter her hostility and
fear subsided, the edema resolved, and her weight gradually returned
to baseline. Subsequently, she has been doing well on clomipramine.
Even though mirtazapine has been reported to be well tolerated
and to have potential value as a treatment for anxiety disorders
(5,6), my patient became more anxious and hostile. The weight gain
of 40 lb was also much higher than reported in the literature. This
case underlines the need for clinicians to be alert to the possibility
of severe idiosyncratic adverse events in patients starting newer
products.
References
1. Burrows GD, Kremer CME. Mirtazapine: clinical advantages
in the treatment of depression. J Clin Psychpharmacol 1997;17 (Suppl
1):34S–39S.
2. Roose SP. Tolerability and patient compliance. J
Clin Psychiatry 1990;60 (Suppl 17):14–7.
3. Stahl S, Zivkov M, Reimitz PE, Panagides J, Hoff
JW. Meta-analysis of randomized, double blind, placebo controlled,
efficacy and safety studies of mirtazapine versus amitriptyline
in major depression. Acta Psychiatr Scand Suppl 1997;391:22–30.
4.Fawcett J, Barklin RL. Review of the results from
clinical studies on the efficacy, safety and tolerability of mirtazapine
for the treatment of patients with major depression. J Affect Disord
1998;51:267–85.
5.Goodnick PJ, Puig A, Devane CL, Freund BV. Mirtazapine
in major depression with comorbid general anxiety disorder. J Clin
Psychiatry 1999;60:446–8.
6. Puzantin T. Mirtazapine, an antidepressant. Am J
Health Syst Pharm 1998;55:44–9.
G Abraham, MD, FRCPC
Kingston, Ontario
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