While being revealing and stimulating, unfortunately not every aspect of the article by Bschor et al. (1) can be applied to outpatient care, as our access to laboratory and ECG services is limited. Therefore, therapeutic drug monitoring (TDM) often remains an unfulfilled dream, as does lithium therapy. Ultimately, what is left—besides the early evaluation of an indication for psychotherapy—are the following steps: Step 1: If patients are rather agitated and present with symptoms such as restlessness, anxiety, loss of appetite, weight loss, aggressive impulses, sleep-maintenance insomnia, and early waking, a presynaptic alpha-2 receptor antagonist (trazodone, mianserin or mirtazapine) should be prescribed; in all other cases, a non-sedating serotonin or norepinephrine reuptake inhibitor (SSRI, NSRI), both in standard doses. However, because of adverse reactions—not because of their efficacy—a change in medication is often required. Many patients treated with mirtazapine become significantly overweight, while those on reuptake inhibitors often develop sexual dysfunction. Only trazodone has neither of these two side effects; however, I think its effect is too weak to warrant its use as a monotherapy. In an outpatient setting, patients have very little tolerance of side effects, especially since they often continue to work or take care of children and the household. Finally, tricyclic antidepressant remain as a third-line treatment; however, they are considered problematic because of their many side effects. In this class, the most suitable agent may be nortriptyline which is only weakly sedative. Step 2: A reuptake inhibitor should be combined with either quetiapine (beware: weight gain!) or with a presynaptic alpha-2 receptor antagonist (trazodone, mianserin or mirtazapine). Step 3: I have seen astonishing improvements with tranylcypromine, but its use is challenging. It requires a diet low in tyramine, long safety intervals, and daily blood pressure monitoring; in addition, many medicines are contraindicated.