Ronald Elson, MD, has been a practicing psychiatrist in Berkeley for 30 years. He is on the staff at University of California, Berkeley, University Health Services and consults with local medical groups. He has seen many trends come and go in the mental health field over the years. Here he discusses the dramatic rise in prescriptions for depression over the past two decades—today one in 10 Americans takes an antidepressant—and what anyone considering antidepressants needs to know to stay healthy.
Why have prescriptions for antidepressants soared since the late 1980s?The use of antidepressants increased nearly 400 percent between 1988 and 2008, mostly among women between the ages of 40 and 59. Today about 10.4 percent of Americans take antidepressants, compared to 6.5 percent in 1999. And the number of people taking antidepressants long-term—more than 24 months—has doubled, from 3 percent to more than 6 percent.
What’s behind this huge increase? I think there are five key reasons.
First, the diagnosis of depression has increased significantly. It’s not clear how much of that increase is due to better diagnosis or social and economic factors. There may be fewer people today who have strong support from extended family or friends. Our population is aging, and that brings its own stresses. We were in a recession for many years. Many environmental factors could play into the rise in depression.
Second, as a culture and a society, we Americans tend to want quick fixes. We don’t want to spend months in therapy talking. We value action—and drugs are one way of getting there. We also tend to think we should be happy, so sadness gets confused with depression, and we think it should be treated, often by medication. Also, the current generation of antidepressants—selective serotonin reuptake inhibitors, or SSRIs, like Prozac and Celexa—are safer and tend to have milder side effects than their predecessors. With a narrower “no muss, no fuss” dosage range, they’re often easier to prescribe.
A third reason is that primary care doctors—not psychiatrists—are now the main prescribers of medication for mood disorders. A problem is that they frequently have 20 minutes max to see each patient. So when someone comes in and says they’re not sleeping well or that they’re not happy with life, there’s typically inadequate time to do a comprehensive work up. Instead, on the basis of a checklist for depression, “Seems like you might benefit from an antidepressant” is a not surprising response. Primary care physicians are doing their best to help patients within a 15- to 20-minute time frame. Data from CDC national surveys, for example, show that the increasing trend in long-term antidepressant use was almost entirely in adults who received their medications from general medical providers.
Fourth, insurance companies prefer not to pay for longer-term therapy if they can go with a monthly prescription, especially since many antidepressants are now available as less expensive generics.
Finally, since direct to consumer advertising of prescription drugs on TV, radio, and in magazines became legal in the mid 80s, we’ve been bombarded by ads implying that anyone who is sad should take a pill to feel better. These ads can generate a false desire for something that not everyone needs. The tremendous increase in long-term antidepressant use gives huge profits to the pharmaceutical industry. At the student health services at UC Berkeley where I work, it used to be that we would have to persuade students to try an antidepressant. Now students often come in and say, “I’d really like Prozac, please.” After a comprehensive assessment, we often have to dissuade them, and urge them to try talk therapy first.
Does it make sense to try talk therapy first, or to do it in conjunction with drug therapy?In most cases, if you have mild to moderate depression, evidence supports the efficacy of trying talk therapy first. But if you are really incapacitated, starting with antidepressants first can be helpful. Antidepressants can improve functioning, hence one’s ability to participate actively in therapy. There’s also good research suggesting that combining talk therapy with medication is more effective than either one alone.
What are the most commonly used antidepressants and how effective are they?The first modern antidepressants— monoamine oxidase inhibitors (MAOIs) and tricyclics—were developed in the 1950s. MAOIs (e.g. Nardil (phenelzine)—are rarely used these days because if they are combined with ingesting a significant amount of particular amino acid, tyramine, they can produce a sudden increase in blood pressure. Tricyclics such as Elavil (amitriptyline) sometimes cause side effects like sedation and weight gain that people obviously don’t like.
The newer class of antidepressants—SSRIs such as Prozac (fluoxetine) and Zoloft (sertraline)—hit the market in the 1980s. They are thought to work by targeting serotonin receptors, altering levels of this mood-boosting neurotransmitter. SSRIs were followed by SNRIs (serotonin norepinephrine reuptake inhibitors) such as Effexor (venlafaxine), which also target norepinephrine receptors. Then there’s Wellbutrin (bupropion), which is thought to work on both dopamine and norepinephrine receptors. Bupropion is often used as an augmenting medication in cases of incomplete response to an SSRI.
What’s surprising is that when it comes to effectiveness, I’m not convinced that SSRIs and related drugs are much more effective than first generation MAOIs and tricyclics. One reason SSRIs like Prozac were marketed so heavily is that the tricyclics were off patent, so drug companies had little incentive to market them. But while they may not be more effective, SSRIs as a class have fewer side effects and are safer than their predecessors—someone who overdoses on a tricyclic is more likely to have life-threatening consequences.
What are the side effects of antidepressants?The newer SSRIs like Prozac can cause headache, irritability, gastrointestinal issues, anxiety, and insomnia. The good news with this class of drugs is that most of these side effects go away in a week or 10 days.
Tricyclics can make you sleepy and cause dry mouth, constipation, and weight gain.
The main issue with MAOIs is that when you eat certain foods like soy sauce or aged cheeses which contain a high level of a particular amino acid, tyramine, there’s a significant risk of a rise in blood pressure, with the possible consequence of a stroke. That’s why they’re not used much anymore. I only prescribe them as a last resort if someone isn’t responding to other types of antidepressants.
What about studies that suggest antidepressants are no more effective than placebos?A number of studies do suggest that improvement from antidepressants is the result of the placebo effect. 60 Minutes reported some time ago that studies that suggest a drug is ineffective are considerably less likely to get published. When you add those results to the results of published studies, the benefit of antidepressants often falls below statistical significance. Most drug studies are funded by drug companies, which means medical professionals—and the public—need to be thoughtful about interpreting the results. A subtle bias can be introduced because academic researchers often believe that if they consistently report negative results, they may lose funding.
That said, in our clinical experience, antidepressants are quite helpful for many people. Research on placebos versus antidepressants may not reflect this for several reasons. Drug studies are typically conducted for just six to eight weeks and don’t follow people six months or a year down the line, when, in our experience, some people do benefit. In addition, good evidence suggests that antidepressants work better for severe depression than for mild to moderate depression. Overall, studies seem to suggest that one third of people get full remission on antidepressants, a third get some positive response, and a third don’t improve.
Interpreting the data isn’t simple. We have to remember that some people may have undiagnosed bipolar disorder and actually get worse with antidepressants. Some people who improve on antidepressants likely get some placebo benefit and some benefit from the drug. In large population drug trials, the results get confounded. Overall I’d say that antidepressants are safe and helpful enough to be worth trying if you are significantly depressed.
Have there been any big antidepressant breakthroughs in recent years?I like to say that recent changes have been “around the edges” as opposed to being radically new advances. They are “me-too” drugs, similar to what’s already available. The reason is simple: It is difficult and expensive to develop a truly new drug, and it takes years to bring it to market. It’s cheaper and easier to take a drug that’s already on the market and substitute atoms on an existing molecule, or come up with a new delivery mechanism for an existing drug. Then, voila! You’ve got a product you can patent. Newer versions of antidepressants with long-acting formulations or other slight variations from the original are likely to come out when the old ones are nearing the end of their patents.
Potentially interesting newer drugs include Viibryd (vilazodone) and Brintellix (vortioxetine). Both seem to have multiple effects at serotonin sites, so each may offer some broader advantages, a benefit to people who have to take more than one antidepressant currently.
There’s also promising research into drugs that affect other neurotransmitter systems beyond norepinephrine, serotonin, and dopamine, such as glutamate and NMDA. Ketamine-related drugs show some promise as rapid-acting agents that may be helpful when someone is in acute suicidal depression. And there’s work being done on the link between depression and inflammation, as well as drugs that impact melatonin, which is linked to healthy sleep.
Transcranial magnetic stimulation (TMS) is an emerging effective noninvasive method used to stimulate small regions of the brain with far fewer side effects than electroconvulsive therapy (ECT).
Are there risks associated with long-term use of antidepressants?So far, no studies have clearly linked long-term use of antidepressants with bad health outcomes. There have been some reports that antidepressants may increase the risk of chronic depression, and this obviously needs to be studied further. However, it’s also important to consider the risk that comes with not taking antidepressants if you need them. You don’t want to leave serious depression untreated because it then becomes even harder to treat.
If you are seriously depressed, we generally recommend trying an antidepressant; and if it works, to continue for a year or so. After that, you can talk with your doctor about whether to continue.
It’s a good idea for women who are pregnant, whenever possible, to come off antidepressants. Some antidepressants have been associated with health problems in babies. But, again, it’s important to balance the small risk of antidepressants with the risk of untreated depression.
Our usual practice is to use the lowest effective dose of a single drug. But in all cases, you need to discuss the risks versus the benefits with your doctor.
What should anyone considering antidepressants know to stay safe and healthy?If you’re on antidepressants, watch out for alcohol. Most antidepressants enhance the effects of alcohol, which means you may have a stronger reaction than you’re used to. Be prudent and safe.
As for marijuana and other recreational drugs, we recommend against them with antidepressants. Marijuana can have a range of mental effects. We don’t have good research on interactions between marijuana and antidepressants. Marijuana affects THC receptors, but also seems to affect others (dopamine, norepinephrine, and serotonin). It’s difficult to assess mental states and whether drug X or Y is working better for you if marijuana is in the mix. Gauging side effects is also difficult because a lot of overlap exists between marijuana and antidepressant effects. Marijuana can theoretically intensify antidepressant side effects. Most important, be sure to tell your doctor about any medications you’re taking—including over-the-counter drugs—to prevent interactions and other potential problems.
Finally, we all need to take an active role in our own recovery and wellness. Any antidepressant should be part of an overall plan. Since many treatments exist and more than one treatment approach may be helpful, people should develop a trusting relationship with their doctors and discuss any concerns fully. Everyday habits—eating, sleeping, and exercising well—have a huge impact on our well-being, regardless of whether or not antidepressants are prescribed.