REVIEW OF: Naito M et al, J Affect Disord 2022;314:27–33

STUDY TYPE: Randomized controlled trial

Peter Kramer’s bestseller Listening to Prozac (Penguin; 1993) planted the idea that SSRIs might treat depression by moderating neurotic personality traits. These patients tend to be easily overwhelmed by everyday stressors. They interpret neutral situations as threatening and frequently react with negative emotions like anxiety, irritability, sadness, and jealousy.

A few studies have tested that theory, but the results are inconclusive. In this new study from Japan, researchers tested a related question: Do baseline personality traits predict response to SSRIs versus mirtazapine in depression?

In this eight-week randomized controlled trial, 154 patients (mean age 46; 42% female) with major depressive disorder were randomly assigned to either mirtazapine or an SSRI (paroxetine or sertraline). The antidepressants were titrated over four weeks as tolerated to maximum doses of mirtazapine 45 mg, paroxetine 40 mg, and sertraline 100 mg. Depressive symptoms were measured at baseline with the Hamilton Rating Scale for Depression, and personality was measured with the NEO Five-Factor Inventory (NEO-FFI) questionnaire. The primary outcome was depressive symptom remission, measured at four and eight weeks. 

Of the five NEO-FFI personality factors (neuroticism, extraversion, conscientiousness, agreeableness, and openness), neuroticism was the most associated with differences in outcomes. This trait describes people who tend to react to everyday stressors with anxiety, anger, depression, jealousy, and self-consciousness (for more on personality traits, see The Carlat Psychiatry Report, March 2022).

Patients with high neuroticism had lower rates of remission with both mirtazapine and SSRIs, but they fared better over the long term with SSRIs. After eight weeks, patients with high neuroticism were more likely to experience remission with an SSRI than mirtazapine (74% vs 36%, p=0.017), but this difference was not seen at four weeks. 

CARLAT TAKE

SSRIs may offer an advantage for patients with high levels of neurotic traits, although the difference may take up to two months to manifest.