Is Statera (mirtazapine) 40mg causing drowsiness and tiredness, and worsening Major Depressive Disorder (MDD) symptoms?

Mirtazapine 40mg and Worsening Symptoms

The drowsiness and tiredness are expected side effects of mirtazapine, but if your Major Depressive Disorder symptoms are worsening, you should switch to a different antidepressant rather than continuing this medication. 1

Understanding the Side Effects

Mirtazapine commonly causes sedation-related adverse effects that you're experiencing:

• Drowsiness and somnolence occur in approximately 23% of patients on mirtazapine versus 14% on placebo, making it one of the most frequent side effects 1, 2
• Excessive sedation affects 19% of mirtazapine users compared to only 5% on placebo 2
• These sedating effects are primarily due to mirtazapine's antihistaminic (H1) activity, particularly at lower doses 3, 4
• Paradoxically, somnolence may actually be less frequent at higher dosages like your 40mg dose, though it still commonly persists 3

The Critical Concern: Worsening Depression

If your depression is actually getting worse on mirtazapine, this represents treatment failure and requires immediate action. 1

The evidence shows:

• 38% of patients fail to achieve treatment response during 6-12 weeks of second-generation antidepressant treatment 1
• 54% do not achieve remission with initial antidepressant therapy 1
• When initial therapy fails, switching to alternative medications (such as bupropion SR, sertraline, or venlafaxine) results in approximately 1 in 4 patients becoming symptom-free 1

Recommended Action Plan

Switch to a different antidepressant immediately rather than continuing with a medication that is worsening your condition 1:

• Evidence from the STAR*D trial demonstrates that switching strategies to bupropion SR, sertraline, or venlafaxine extended release show no significant differences in efficacy among these options 1
• Bupropion is particularly advantageous if you want to avoid sedation, as it is activating rather than sedating and has lower rates of sexual side effects 1
• Switching is equally effective as augmentation strategies (adding another medication to mirtazapine), so a clean switch is reasonable 1

Important Caveats

Distinguish between side effects and worsening depression:

• If you're only experiencing drowsiness/tiredness but your mood, interest, concentration, and other depression symptoms are actually improving, the sedation may resolve with time 3
• However, if core depressive symptoms (low mood, anhedonia, hopelessness, suicidal thoughts) are worsening, this is treatment failure requiring immediate medication change 1

Common pitfall to avoid: Do not simply wait hoping the sedation will improve if your depression is genuinely worsening. The evidence shows that treatment-emergent side effects like drowsiness tend to persist during the first 3 months rather than resolve 5

Discuss with your prescriber:

• The specific nature of "MDD worse" - are core symptoms deteriorating or just sedation affecting function?
• Switching to a non-sedating alternative like bupropion, sertraline, or venlafaxine 1
• Tapering mirtazapine over 10-14 days when switching to limit withdrawal symptoms 1