As some of you may know, I have suffered from depression for…well, ever, I suppose. I’m doing well with pharmacological treatment, taking 30mg of fluoxetine a day, which makes me much more even-keeled and much less despondent.
But I didn’t start out with fluoxetine. I started with Lexapro which, like fluoxetine, is a Selective Seratonin Reuptake Inhibitor (SSRI). Lexapro didn’t really work for me, though, and after a few months I stopped taking it, assuming that it was proof that I didn’t really have clinical depression.
One divorce later, I moved on to Effexor (venlafaxine), a Seratonin-Norepinephrine Reuptake Inhibitor (SNRI), but due to insurance issues, I only took that for a month, which isn’t long enough to tell you anything about whether a drug works or not. Once I got back onto insurance, I ended up on Strattera (atomoxetine), a NRI, which helped me with long-ignored ADHD, and helped my mood somewhat.
About a year after my divorce, I looked into gastric bypass surgery. I’m sure my friend and colleague Kate Harding can tell you many fun and exciting facts about that particular surgery; suffice to say that it turns out if they surgically remove your stomach, you may, in fact, lose weight because of it. Or, you know, die.
Fortunately, the clinic I went to did psychological screening before surgery. And the screening showed that I was…surprise!…deeply depressed.
And so I went back into the doctor and got on fluoxetine, and went into therapy and got a good therapist, and in the end, I was, if not cured, then in a much better place overall. (I never did get my stomach removed.)
A good many of you out there who are on antidepressants are nodding along with parts of my story. And that’s because of a little-known fact about antidepressants: many, if not most people, don’t get on the right antidepressant the first time. Or the second time. Or even the third time.
There’s hopeful news today that this may be changing:
Scientists have identified genetic variations that affect specific neurotransmitter functions, which could explain why some patients respond to some drugs but not to others. For example, some depressed patients who have abnormally low levels of serotonin respond to S.S.R.I.’s, which relieve depression, in part, by flooding the brain with serotonin. Other depressed patients may have an abnormality in other neurotransmitters that regulate mood, like norepinephrine or dopamine, and may not respond to S.S.R.I.’s.
In a report last October in the journal Science, Dr. Francis Lee, a colleague of mine at Weill Cornell Medical College, identified a genetic mutation that could potentially predict patients’ responses to an entire class of antidepressants.
He inserted into a mouse a defective variant of the human gene for brain-derived neurotrophic factor, a protein that is increased in the brain with S.S.R.I.treatment and is critical to the health of neurons. Then he subjected these “humanized” mice to stress and found that they did not respond to Prozac with decreased anxiety. The clear implication is that people with this variant will not be able to respond to any S.S.R.I., which requires normal neurotrophic-factor function to work. A psychiatrist could identify this genetic variant and then steer his patient to a different class of antidepressants.
Furthermore, other genes may play a role in the adverse effects of antidepressants that have made recent headlines: suicidal behavior. Recent evidence shows that a small number of depressed adolescents and young adults experience an increase in suicidal feelings and thoughts when they are treated with S.S.R.I.’s, compared with a placebo. It is entirely possible that a genetic variation in one or more genes that regulate serotonin function makes these people feel briefly more suicidal, rather than less, when exposed to the drugs.
This is potentially very good news for those suffering with depression. Getting on the right medication from the start is very important — and getting on the wrong one can be very dispiriting. It takes a month to get a read on whether the drugs are working — and wasting three months when life doesn’t feel worth living anyhow is difficult, to say the least. It’s very, very easy to find oneself giving up on treatment. I did it twice. And I know I’m not unique.