George Porter, a 47-year-old engineering librarian from La Canada Flintridge, first became depressed after his father's heart attack nearly seven years ago. The married father of two was overcome with sadness that wouldn't go away and lost pleasure in activities he'd once enjoyed. "I'd been a voracious reader all my life, and I found it almost impossible to get through a book," he said. He often began sobbing uncontrollably.
Porter followed his doctor's advice to see a psychologist and take medication, cycling through at least half a dozen drugs. Many helped, but none worked completely.
Although doctors have more than 20 medications to choose from when prescribing a treatment for depression, there's still little way to know which drug will work for a particular person. Many people need to try two or three drugs or drug combinations before experiencing relief. Some go through six or more. "It's a hit-or-miss, trial-and-error kind of process," said Dr. Richard A. Friedman, a professor of clinical psychiatry at Weill Cornell Medical College.
Patients have finally come to recognize depression as a treatable illness with an underlying biological cause rather than misconstruing it as a sign of weakness. Doctors are able to help more people than ever with depression simply because more people are coming to their offices for treatment. One might expect that this increase in patients would lead to a new sophistication in choosing which drug might work for a particular patient.
That's not the case.
A review article in the November 2008 issue of the Annals of Internal Medicine looked at more than 200 studies of 12 second-generation antidepressants -- primarily selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Zoloft and serotonin and norepinephrine reuptake inhibitors (SNRIs) such as Effexor and Cymbalta -- and concluded that no substantial differences existed in how well they worked.
Although a more-recent review in the Lancet of the same 12 drugs concluded that certain ones worked better than others, that analysis has been criticized for reading too much into studies that are largely funded by the drugs' manufacturers.
"There's no clear evidence that one antidepressant is more effective than another," said Dr. Ian A. Cook, director of depression research at UCLA's Semel Institute for Neuroscience and Human Behavior. Even if modest differences do exist among antidepressants, he said, patients vary widely in what will work for them.
Depression is a common condition, affecting nearly 15 million Americans a year and one in six over their lifetime. The most common treatments are counseling and drugs, with a combination of the two working best.
The most effective way for a doctor to find an antidepressant that works is to look at the patient's history, because someone who has already been treated for depression will often respond to a medication that worked before. There's also a chance that someone with a family history of depression could benefit from the same drug that helped a parent or sibling.
Beyond these factors, "there is not a good way to know what medication is going to be the best for your patient," said Dr. Raymond J. DePaulo Jr., a professor of psychiatry at the Johns Hopkins University School of Medicine. Cost has become less of a concern now that most antidepressants are available in generic form for less than $20 a month, so the decision usually comes down to side effects.
Antidepressants are believed to work by blocking the reuptake of neurotransmitters such as serotonin, norepinephrine and dopamine, increasing the amount available in the synapses.
Doctors generally start by prescribing one of the SSRIs because drugs from this class are less dangerous in overdose and are least likely to cause serious side effects. Common side effects of SSRIs include nausea, weight gain and impaired sexual function. Other newer drugs include the SNRIs, which have side effects similar to those of SSRIs but may cause weight loss instead of weight gain, and the dopamine reuptake inhibitor Wellbutrin, which is less likely to cause problems with sexual function but may cause seizures.
Older drugs tend to cause more side effects. For example, monoamine oxidase inhibitors (Nardil and Parnate among them) can interact dangerously with other drugs and even some foods, and tricyclics (such as Pamelor) can increase heart rate and cause people to become dizzy when they stand. Tricyclics can also cause drowsiness, dry mouth and constipation.
Another approach is to choose a drug based on the subtype of depression.