Medical Edge Newspaper Column

Finding the Antidepressant That's Right For You

March 11, 2007
Dear Mayo Clinic:
I first tried several antidepressants, which did not help. But in the past three years I have been using venlafaxine (Effexor), and am doing well. Are there any harmful effects from using this drug for a long time? Without it, my symptoms start to return. And why would one antidepressant work when others haven't? -- Lemont, Ill.

Answer:
I am happy to hear you have seen improvement. And I'm glad to address your excellent question, which raises several interesting issues regarding antidepressant medications.

Some people can taper off their antidepressant after a year or so and remain in remission. Lifestyle changes may have increased their resiliency, or perhaps psychotherapy helped "immunize" them to recurring depression.

But symptoms return for many, meaning that they need to stay on their antidepressant, as you discovered. Take heart, though. Despite millions of individuals taking one or more of a variety of common antidepressants for many years, we have not noted any cumulative long-term harmful effects.

It's possible that you stopped taking venlafaxine too abruptly. It's important to taper off slowly, extending the taper over several weeks under your physician's direction. When you stop too quickly, you may experience so-called "discontinuation symptoms," which can masquerade as relapse.

The other experience you report -- not responding to initial antidepressant treatment -- is actually all too common. Your story illustrates an important lesson: people should not give up, as perseverance may lead to eventual response. That point was driven home by a large multi-center study sponsored by the National Institute of Mental Health over the past five years -- the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. It demonstrated that patients with persistent depression can get well after trying several different medication strategies.

Though you did not specify which antidepressants you initially used, first-round treatment of depression is often with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), or escitalopram (Lexapro). These are safe and effective for many people, but there is growing evidence that some types of depression respond better to different classes of antidepressants. Your current antidepressant, venlafaxine (Effexor) -- a drug from the serotonin and norepinephrine reuptake inhibitor (SNRI) class -- is one such alternative.

Your insufficient response to the first several antidepressants tried could have something to do with how your body metabolizes them. We know that a small but significant minority of people are ultra-rapid metabolizers of certain antidepressants. If you are one of these, you might have taken a good dose of an effective antidepressant but did not obtain sufficient blood levels of the drug simply because your body processes it too rapidly. On the other hand, we sometimes hear from folks who, because they are unusually slow metabolizers of certain antidepressants, experience intolerable side effects and soon stop the drug.

In other words, finding the right antidepressant can be a trial-and-error process, as you have learned. Given that it usually takes some four to eight weeks for any single drug to show its full effect, that process can be long and sometimes unpleasant.

We are just beginning to be able to determine from the outset which class of antidepressant and which dosage might be most useful for a particular patient by studying their genetic make-up. This exciting area of investigation will no doubt contribute to increasingly individualized medical care in the years ahead.

In the meantime, please note that medications are not the only treatment for depression. Psychotherapy is also an important option, and pursuing it -- even if only in a short-term, goal-oriented way -- together with the use of antidepressants can be an especially effective combination. This too may require some trial and error, as the success of therapy depends on finding a psychiatrist or psychologist with whom you are comfortable. Specialized and supervised group therapy, such as bereavement groups, stress-management classes, marital counseling and family therapy, also may help.

-- Donald E. McAlpine, M.D., Psychiatry and Psychology, Mayo Clinic, Rochester, Minn.