Immediate Management of Mirtazapine-Induced Anger
Discontinue mirtazapine immediately and do not restart it, as anger and irritability are recognized adverse effects that can occur early in treatment and may represent a serious behavioral change requiring medication cessation. 1
Discontinuation Protocol
- Stop mirtazapine now (patient has already been on it for only 8 days, which is a short duration that minimizes withdrawal risk) 1
- No taper is necessary given the brief 8-day exposure period 1
- The patient's self-initiated dose reduction to half a tablet demonstrates the severity of symptoms and confirms the medication is not tolerable 1
Alternative Antidepressant Selection
Switch to bupropion as the next antidepressant choice, as it has a different mechanism of action (norepinephrine-dopamine reuptake inhibitor rather than a serotonergic agent) and may be better tolerated in patients who experienced adverse effects with both sertraline and mirtazapine 2
Rationale for Avoiding Serotonergic Agents
- The patient already experienced pruritus with sertraline (an SSRI), which can occur due to serotonergic effects on skin receptors 3, 4
- Mirtazapine, while having antihistaminic properties that can treat pruritus 5, 6, also has serotonergic effects that may have contributed to the behavioral changes 1
- Switching between different serotonergic antidepressants (SSRI to mirtazapine) showed no advantage in this patient 2
Specific Prescribing Instructions
Start bupropion SR 150 mg once daily in the morning, with potential increase to 150 mg twice daily after one week if tolerated 2
- Bupropion has demonstrated equivalent efficacy to SSRIs for depression treatment 2
- It has a lower risk of the specific adverse effects this patient has experienced (pruritus, behavioral changes) 2
- Morning dosing minimizes insomnia risk 2
Monitoring Plan
Schedule follow-up in 2 weeks (not 6 weeks as originally planned) to assess:
- Resolution of anger symptoms after mirtazapine discontinuation 1
- Tolerability of bupropion 2
- Depression symptom response 2
- Any emergence of suicidal thoughts or worsening depression 1
Critical Safety Considerations
- Monitor for worsening depression or suicidal ideation during the transition period, as this is a vulnerable time when changing antidepressants 1
- Instruct the patient to call immediately if anger persists beyond 3-5 days after stopping mirtazapine, as this would suggest the symptom may not be medication-related 1
- Avoid reintroducing any serotonergic antidepressants (SSRIs, SNRIs, mirtazapine) given this patient's pattern of adverse effects with two different serotonergic agents 2, 3
Common Pitfalls to Avoid
- Do not attempt to "push through" behavioral side effects like anger by continuing mirtazapine at a lower dose, as behavioral changes can represent serious adverse drug reactions requiring discontinuation 1
- Do not switch to another SSRI or SNRI (such as escitalopram, duloxetine, or venlafaxine), as the patient has now demonstrated intolerance to serotonergic mechanisms with both pruritus and behavioral symptoms 2, 3
- Do not delay follow-up for 6 weeks when a patient reports severe behavioral adverse effects, as closer monitoring is essential during antidepressant transitions 1