The time to efficacy with mirtazapine is approximately 2 to 4 weeks, but anxiety symptoms and poor sleep or insomnia may improve in the first week.8 Studies have suggested the possibility of a more rapid onset of efficacy with mirtazapine than with SSRIs, as well as potential response acceleration in MDD and other psychiatric illnesses such as anxiety disorders or obsessive-compulsive disorder (OCD).9,10 A review that included several double-blind studies and compared mirtazapine with SSRIs found the amount of responders with persistent improvement with onset in Week 1 was more pronounced with mirtazapine.9
Augmenting an SSRI with mirtazapine is a potential therapeutic option because it can help boost the efficacy of the prescribed SSRI while enhancing appetite and blunting the activating or anxiety-like effects of some SSRIs, which may help with relaxation and sleep.4 The combination of an SSRI plus mirtazapine has been studied in patients with MDD, posttraumatic stress disorder, and OCD; it was found to improve symptoms of those conditions due to the medications’ complementary mechanisms of action.4,11-13 Also, mirtazapine has been shown to decrease the rates of relapse after an acute phase of depression.4,14
OUTCOME Rapid improvement
On Day 9, Mr. J receives the first dose of mirtazapine, 7.5 mg at bedtime. On Day 10, when Mr. J wakes, his mood is notably improved. He is more interactive (sitting up in bed reading and making eye contact with the staff during an interview), and he reports improved sleep and eats most of his breakfast.
After receiving 3 doses of mirtazapine, Mr. J reports that he feels back to his normal self; he is interactive, alert, and eating well. Due to the rapid improvement in mood, ECT is discontinued, and he does not receive any ECT treatment during the remainder of his hospitalization.
On Day 11, divalproex is discontinued. Because Mr. J receives only 5 days of therapy with this agent, his divalproex level is not checked. At this point, the treatment team feels confident in ruling out bipolar disorder.
On Day 15, Mr. J is discharged with sertraline, 200 mg/d, mirtazapine, 7.5 mg/d at 7 pm, aripiprazole, 20 mg/d, clonazepam, 1 mg twice daily as needed for anxiety, melatonin 5 mg/d, and adalimumab, 40 mg IM every 2 weeks. Discharge instructions include a follow-up in 2 weeks to evaluate continuation strategies for the discharge medications.
Ten months after his depressive episode, Mr. J has had no further admissions at the hospital where he received the treatment described here.
Bottom Line
Evidence for the treatment of major depressive disorder induced by corticosteroid withdrawal is limited. Despite trials of agents from multiple medication classes, the depressive episode may not improve. Adding mirtazapine to a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor may prove successful.
Related Resources
- Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;(12):CD006528.
- Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011;65(6):549-560.
Drug Brand Names
Adalimumab • Humira
Aripiprazole • Abilify
Bupropion • Wellbutrin, Zyban
Buspirone • Buspar
Clonazepam • Klonopin
Diazepam • Valium
Diphenhydramine • Benadryl
Divalproex • Depakote, Depakote ER
Lithium • Eskalith, Lithobid
Mirtazapine • Remeron
Prednisone • Deltasone
Sertraline • Zoloft