Antidepressants: New Risks of Side Effects

Antidepressants help many people. But evidence has been growing for years that the widespread use of these medicines is not justified, and that consumers should be more circumspect about taking them. The latest news supporting a more cautious approach is a study linking 2 antidepressants — fluoxetine (Prozac, Sarafem) and paroxetine (Paxil) — to birth defects.

Some of the mounting concern attaches to such newly discovered side effects and to safety concerns that have arisen over the past 15 years. But it also revolves around an ongoing debate over just how effective the drugs are and for whom they drugs should be prescribed.

Despite these concerns, antidepressant use has not abated. Between the periods 1988–1994 and 2007–2010, the proportion of people 18 or older who had ever taken an antidepressant increased more than fourfold, from 2.4% to 10.8%, according to the CDC report Health, United States, 2013 (pdf). On any given day in the US, between 10% and 12% of adults are taking an antidepressant; the proportion is higher for women.

Putting it concretely, then, circa 2015: Paroxetine and fluoxetine should never be prescribed to pregnant women or, frankly, any sexually active woman of childbearing age.

That makes the birth defect issue particularly worrisome. The latest and largest study of this link was published recently in the British Medical Journal (BMJ). It was a statistical analysis of data on 28,000 women from the US National Birth Defects Prevention Study, and focused on a group of 5 SSRIs (Selective serotonin re-uptake inhibitors), which are the most widely prescribed type of antidepressant.

The study supported previous research linking 2 birth defects with fluoxetine and 5 with paroxetine, including heart defects, anencephaly (in which a baby is born without parts of its skull or brain), and abdominal wall defects. Notably, although the birth defects occurred 2 to 3.5 times more frequently among infants of women taking paroxetine or fluoxetine early in pregnancy, the absolute risk was very low. For example, the rate of anencephaly among women who had taken paroxetine  was 7 in 10,000 births, compared to 2 in 10,000 for women who had not taken paroxetine or any antidepressant.

“It’s a doubling or more in some cases,” said lead researcher Jennita Reefhuis, PhD, an epidemiologist with the National Center on Birth Defects and Developmental Disabilities at the CDC. “But a doubling of a small risk is still a small risk.”

The finding adds emphasis to a 2005 FDA safety alert on paroxetine, which warned of a possible association with heart defects.

Putting it concretely, then, circa 2015: Paroxetine and fluoxetine should never be prescribed to pregnant women or, frankly, any sexually active woman of childbearing age.

Reassuringly, the study found no increased risk of birth defects among women who took 3 other SSRIs: citalopram (Celexa), escitalopram (Lexapro) and sertraline (Zoloft).

Downsides to Antidepressants

Does that mean pregnant women or women of childbearing age who become depressed should feel comfortable taking one of those 3 medicines? Maybe not. It deserves a thorough discussion with your doctor.

While much is still unknown about antidepressants despite the large numbers of people taking them, the weight of both solid and circumstantial evidence has become clearer over the last decade: For all but the most severely and chronically depressed people, antidepressants should be taken far more cautiously and sparingly, and usually not as initial treatment for most people. Here are 3 major reasons for this caution:

1. Antidepressants are overused in people who have situational or short-duration depression, or depression linked to a traumatic or upsetting life event. (See more on this below)
2. They are at best 50% effective, with a significant placebo effect linked to the simple passage of time.
3. The side effects can be unpleasant and sometimes dangerous.

This cautious view of antidepressants is at odds with the societal take on the drugs in the 1990s and early 2000s that is most closely associated with 2 books: Peter Kramer’s Listening to Prozac (1997) and Elizabeth Wurtzel’s Prozac Nation (2002). Both extolled the wonders of the new “better living through neurochemistry.”

There’s not space here to tell the whole antidepressant story. Suffice it to say that antidepressants — both the old ones and the newer SSRIs — have not lived up to that promise, nor the hopes of millions of people who experience a bout of depression.

More recent books — The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder by Allan V. Horwitz and Jerome C. Wakefield (2007); Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression by David Healy (2007); and The Emperor’s New Drugs: Exploding the Antidepressant Myth by Irving Kirsch, PhD (2011) — contain full descriptions of the overselling and overuse of antidepressants.

A shorter read, uniquely grounded in the research evidence, and with easy-to-understand practical advice, can be found in Consumer Reports Best Buy Drug’s report on antidepressants, published in 2013 but still close to state-of-the-art today. I know this report well since I wrote earlier editions of it as managing editor of Consumer Reports Best Buy Drugs.

For the sake of family members and friends who found themselves caught in the throes of what William Styron called Darkness Visible (1990, one of the best books ever written about the experience of depression), I had hoped that the evidence would support antidepressants. Simple — you take a pill. But in reality, it’s not that simple.

Here’s a digest of the most salient insights and advice from the Consumer Reports Best Buy Drugs report:

If you have 5 or more of these symptoms persistently for several weeks you are almost certainly depressed and should seek counseling and treatment.

• Decreased energy, fatigue, and motivation; feeling slowed down
• Depressed mood and negative thinking and outlook
• Difficulty concentrating, making decisions, and coping with life’s daily challenges
• Feeling restless, anxious or fidgety
• Feelings of worthlessness or inappropriate guilt
• Insomnia, early morning awakening, or oversleeping
• Loss of interest or pleasure in hobbies, work and recreational activities you usually enjoy, including sex
• Recurrent thoughts of death or suicide; suicide attempts
• Substantial weight loss or gain or appetite changes (eating significantly less or more)

Sometimes depression is normal

Don’t resort to antidepressants first if your depression occurs in the wake of a traumatic or stressful life event, such as the death of a loved one, diagnosis with an serious illness, divorce, job loss or problems at work, marital strife, etc. Feeling depressed at such times is normal. This is sometimes called “situational” depression. If you’re still able to function and have no prior history of depression, your symptoms will usually ease or disappear completely within a few weeks or months, aided, if necessary, by family support and professional counseling.

Seek help when you need it

If you have 5 or more symptoms of depression (see above), are not functioning well and your symptoms have persisted for at least 3 weeks, you’re more likely to be a candidate for trying an antidepressant. That’s especially true if there is no apparent reason for you to be depressed or if you have had repeated episodes of depression.

Talk to your doc about side effects

The majority of people who take an antidepressant (about 60%) experience at least one side effect. About 12% find the side effects so intolerable that they stop taking the medicine. Talk with your doctor if you find a side effect unacceptable. He or she may recommend trying another antidepressant or suggest counseling and other lifestyle changes to address sources of the depression.

Sex is an issue

Studies indicate and drug companies say that between 5% to 15% of people who take an antidepressant experience a decline in interest in sex or difficulty achieving an erection, arousal or orgasm.

However, a 2010 Consumer Reports survey found that 23% to 36% percent of respondents had sexual problems associated with the use of some antidepressants. Since depression itself can make people lose interest in sex, it’s important to determine whether it is the antidepressant or the illness that’s causing the problem — not always an easy distinction. The same goes for suicidal thoughts.

Consider the side effects of different drugs

Talk with your doctor about the differences among antidepressants in terms of side effects. This may well affect your choice. Table 4 on page 11 of the Consumer Reports Best Buy Drugs report summarizes the evidence on the effectiveness of antidepressants and the rate at which people stopped taking each antidepressant because of side effects. The table also has comments on some of the strengths and identified problems with each drug.

It might not only be depression

Be very specific with your doctor and/or therapist about your symptoms if you think you’re depressed. People who also have anxiety along with depression (a common combination) usually need more tailored treatment and different medicines and psychotherapeutic approaches.

Consumer Reports has a printable pdf version of the Best Buy Drugs report for Antidepressants.