MF: Because chocolate will have a response rate comparable to placebo, which is 30-40%, which will not match what you get with antidepressants. Which antidepressant is not as crucial as establishing a communication that allows you to change the course of treatment.
JEA: In infectious disease, getting it right on the first shot is the main issue. You get a blood or sputum culture, it tells you what the microbe is and what drug it's sensitive to, you prescribe a short course of antimicrobials and that's it. We, by contrast, are in it for the long term. The process of selecting a first-line antidepressant sets the stage for long-term management. A person will need to take an antidepressant for at least six months; side effects and other concerns will arise that we'll try to address.
AAN: Reasonable data suggest that after someone begins to respond to an antidepressant they have to be on it for another four months minimum. That usually translates into a year. Some people need to take it longer: those who've had three or more episodes in their lifetime, those above age 50 who have had two episodes, those who have had double depression, which is dysthymia, a smoldering more mild depression, on top of a major depression.
HEM: Once someone starts responding, what might make you change course?
MF: There are side effects that arise in the short term, side effects that arise in the short term and continue, and others that kick in three or four months into treatment. The one comparative study we did showed that Paxil caused more weight gain than other SSRIs after six months.
HEM: Do subtypes of depression guide you at all?
MF: MAO inhibitors have repeatedly been shown to be superior to tricyclics in the treatment of depression with atypical features. However, practically speaking, nobody uses MAOIs first-line because diet and medication restrictions are really onerous.
In general I use subtypes for what to do next. In melancholic depression, dual-action agents—Anafranil, Effexor, Remeron—may be better than single-action ones. In atypical depression, drugs that affect dopamine, like MAOIs, may be efficacious.
At best, the difference between drugs in effectiveness in a subtype is maybe 20%. What is a 5% difference? There are compounds on the horizon that are of theoretical interest for subtypes. People with pain or melancholic features may be particularly responsive to duloxetine, a balanced dual-action agent (equally active on both serotonin and norephinephrine systems). Gepirone may be particularly efficacious in atypical depression. The NK-1 [substance P] antagonists may work in diffferent subtypes. The CRF antagonists may be good drugs for people with PTSD. We need empirical evidence. We don't have it yet.
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