November, 1998
November, 1998
by Alex Markels
Call it an experiment in worse-living-through-chemistry. Last year, brain reseracher Dr. J. Douglas Bremmer gathered up a group of former depression patients and intentionally induced in them a state of woe the likes of which they hadn't felt since their darkest days. The Yale University psychiatrist had each patient down a cocktail spiked with an amino acid that blocks, for up to six hours, the brain's ability to absorb serotonin, the sanguinity-inducing neurotransmitter without which the depression-prone slip into a dismal funk. He then took pictures of each person's brain with a special camera that captures brain activity as a series of glowing multicolored blobs.
This was some cruel Dr. Feelbad ruse to force people to relive their misery. The good doctor instead sought to pinpoint the parts of the brain responsible for triggering depression --- in hopes of finding better, more targeted waysof fighting the disease.
But what was most fascinating abou the experiment wasn't the pictures --- of even that they did, in fact, reveal depression-related changes in the three brain regions. What surprised Dr. Bremmer, rather, was the starkly gender-specific ways in which men and women reacted to the potion. Typical of the males was "John," a middle-aged businessman who had fully recovered from a bout of depression, thanks to a combination of psychotherapy and Prozac. Within minutes of drinking the brew, however, "he wanted to escape to a bar across the street," recalls Bremmer. "He didn't express sadness … hedidn't really express anything. He just wanted to go to Larry's Lounge."
Contrast John's response with that of female subjects like "Sue," a mother of two in her mid-thirties. After taking the cocktail, "she began to cry and express her sadness over the loss of her father two years ago," recalls Bremmer. "She was overwhelmed by her emotions."
Venus and Mars, indeed. Although depression appears to have the same biological triggers in both men and women, we often experience it as if we were, literally, from different planets. Which begs the question of whether depression in men and women is, as Bremmer supposes, "different kettles of fish," and, of so, whether treatments could therefore be improved by tailoring them specifically for each sex.
GENDER BLUES
Until recently, depression research and treatment have been aimed mostly at women. Conventional psychotherapy generally focuses on plumbing the sorts of heart-wrenching emotional issues that are routinely addressed by women but often give men the heebie-jeebies. And while such modern antidepressants as Prozac and Zoloft (which are both selective serotonin inhibitors, or SSRIs, drugs that keep the brain awash in serotonin) aid both genders, their sexual side effects tend to afflict men more severely, causing impotence and libido loss so unbearable that many end up blowing off treatment altogether (though more sex-friendly pills do exist). Combine that with a genetic and cultural predisposition to "hanging tough" and feigning emotional invulnerability, and it's little wonder men are about two-and-a-half times less likely than women to seek help in the first place.
Indeed, some experts believe that male depression is vastly underreported for that very reason. "It's a hidden epidemic," says Terrence Real, the codirector of the Family Institute of Cambridge Gender Research Project, whose recent book, "I Don't Want to Talk About It: Over coming the Secret Legacy of Male Depression --- unexpressed melancholy masked by substance abuse and antisocial behavior --- is widespread among men.
Many men are simply ignorant of the possibility that they might be depressed. Take "Bob," a 45-year-old attorney who thought he was having a midlife career crisis. "I've never really liked what I do," he told Dr. Thomas Wise, a psychiatrist and depression expert at Inova Fairfax Hospital in Virginia. "I just went to law school because it was expected of me."
But something about Bob's complaints didn't ring true. His previous fascination with the law had led him to publish two books about his specialty, and he was teaching a law course at a local college. "it sure didn't sound like he'd always hated his work," says Wise. Moreover, Bob complained of chronic fatigue. He loved to eat but had recently lost his appetite and shed 10 pounds. He had always loved to golf and play cards, but he no longer had interest in such diversions. "These were classic symptoms of depression," says Wise. "But when I suggested that maybe he was depressed, he frowned and said, 'I'm not so sure.' "
FLIRTING WITH DIVORCE
At least Bob knew something was wrong and had the gumption to seek help. Too many men simply "hold on to depressive pain until it becomes unbearable," says Dr. Frederick Goodwin, the former director of the National institute of Mental Health and a leading expert on depression. "And the result is failed health and failed relationships."
Indeed, each year roughly 23,000 American men commit suicide (four time more than women), while countless others suffer depression-related heart disease. Moreover, there's increasing evidence that untreated or undertreated depression --- particularly that experienced early in life or during highly stressful periods, such as combat duty --- may damage the brain's hippocampi, to seahorse-shaped parts of the limbic system believed to regulate emotions, as well as memory, appetite, and sleep. Bremmer's studies of war veterans suffering from post-traumatic stress disorder suggest that hormones released during periods of intense stress may shrink the hippocampi. The likely result: a predisposition to depression later in life. "Severe stress and mental trauma is a predictor of depression," says Bremmer, who points to research that demonstrates half of all people who suffer major depression will experience a recurrence of the condition.
Such waves of misery can push even the most committed relationship to the breaking point. And when we complain that we've "fallen out of love" with our partners or spouses, the truth may be that our gloomy outlook is responsible for our change of heart. "If you're on a long-standing relationship and it suddenly seems unsatisfying, you need to consider the possibility that you're suffering from depression," says Dr. Peter Kramer, author of Listening to Prozac and Should You Leave?, in which he cites studies showing that depression and marital troubles often go hand in hand.
Depression's judgement-clouding effects are reason enough to get evaluated mentally before making any final decisions about ending a long-term relationship. "Unrecognized depression is one of the greatest risk factors for divorce," says Kramer. "And I'd hate for a marriage to end because of an unrecognized treatable illness."
A host of antidepressant and psychotherapy treatments introduced over the past three decades has, in fact, helped boost recovery rates to nearly 90 percent." The real tragedy of men's failure to seek help is that depression is highly treatable," says Real. "There's really no good reason not to get help."
DON’T BE A MAN
So why do men continue to resist diagnosis and treatment? The answer probably lies in some tangled combination of nature and nurture, and genetic and cultural makeup passed down through generations and perpetuated by every John Wayne or Clint Eastwood move ever made. "It's how we're raised," says Real. "To learn to be a man means to pretend to be invulnerable … to play through the pain .. to tough it out. The very phrase 'Be a man!' means 'Stop being vulnerable!' "
"Natural selection chose men would could redirect or contain their emotional responses," says Dr. Helen Fisher, an evolutionary anthropologist at Rutgers University and the author of "Anatomy of Love: A Natural History of Mating, Marriage and Why We Stray. "If you're looking into the yellow eyes of a leopard coming your way, it's not adaptive to experience your emotions. You have to concentrate on killing the beast. Reveal your heart and you perish."
Yet in a modern world in which day-to-day survival is largely a given, or predisposition to turn melancholy and anguish into anger and aggression is only slightly more useful than our vestigial appendixes. "The very mechanisms that evolved to help contain men's emotions can also short-circuit their ability to cope," sys Fisher, who believes men a susceptible to "emotional flooding," an explosion of pent-up feelings that often takes to form of violence. "Your heart pounds, your face gets red, and you do dumb things like drive too face, drink too much, and put your first through walls."
Which isn't exactly the kind of behavior that fosters healthy relationships, let's alone self-actualized men. And whether or not we're willing to admit it, we need emotionally intimate connections in order to do more than just survive. "Ultimate satisfaction is attained through intimate contact," says Dr. Drew Pinsky, the medial director for chemical dependency services at Las Encinas Hospital in Pasadena, California, who says his depressed male patients have a host of problems ---- both physical and emotional --- with expression intimacy. "Men are just pathetic at that."
THE PROZAC DROOP
Ironically, while all those serotonin-enhancing drugs can help break down male inhibitions about exploring emotional intimacy, their side effects have also created major hurdles to our favorite way of expressing it: Approximately 60 percent of men who take SSRIs report impotence, reduced sexual pleasure, or decreased libido (see Antidepressant Pros and Cons sidebar). Such reactions can worsen the deadening effect depression itself can have on sex drive, sabotaging any chance for successful treatment.
That's exacerbated by our reticence to discuss sexual dysfunction with doctors, as well as the failure of some internists to thoroughly explain the potential for sexual side effects. Most disturbing about the malign neglect is the fact that Wellbutrin and Serzone, two antidepressants that are largely free of sexual side effects, are often overlooked. "People just aren't as familiar with Wellbutrin as with Prozac or Zoloft," says Inova Fairfax Hospital's Wise, who also believes Wellbutrin may be under-prescribed because it needs o be taken twice daily, versus the single dose of most SSRIs. "But that's not a good enough reason to avoid Wellbutrin. It should be a first-line treatment for men, instead of SSRIs."
Althoguh Wise recommends that those who suffer acute sexual dysfunction due to SSRIs consider switching medications, there are other options as well. Many men need only reduce their dosage of SSRIs to restore sexual drive, while others find relief by taking "drug holidays," two-day breaks from medications during which virility is restored, though the depression-alleviating effects of SSRIs aren't damaged. (Either approach should be discussed with a doctor first.)
THE TALKING CURE
Men whoare averse to spending time on the psychiatric couch my look forward with relish to the day when pharmacologists develop the real-world equivalent of George Orwell's SOMA --- a miracle cure for all symptoms of depression. But for the time being, pills alone typically aren't enough. Studies show that the likelihood of depression's recurring increases substantially when psychotherapy isn't in the treatment mix. "While antidepressants alleviate depression's symptoms," sys Dr. William S. Pollack, the codirector of the Center for Men at Harvard Medical School's McLean Hospital. "they can't take away the trigger for the stress."
Pollack cites studies indicating that psychotherapy may have the same biological effects as antidepressants, increasing the brains uptake of serotonin and inducing a sense of well-being --- without any side effects. Yet research also indicates that talk therapy without medication often prolongs treatment, risking the possibility that men might succumb to their suicidal tendencies. "[Antidepressants] give men back the capacity to do something about their depression," Pollack says.
"Doing something" doesn't necessarily mean undergoing the kind of intense emotional introspection that women tend to excel at during therapy but that terrifies some men so thoroughly that they flee from treatment. "Men have this false notion that therapy is only talking about feelings," says Pollack. "It's really talking about whatever things are essential in their lives --- their sense of struggle at work, the sense of failure or success at achieving the goals in their lives."
In fact, he believes the key to improving depression treatment for men may lie in changing the "feminized" mode most psychotherapists now employ. Instead of forcing men to explore their inner selves right off the bat, he favors an approach that doesn’t threaten their fierce sense of emotional invulnerability but instead offers the kind of advice and consultation that physicians treating physical ailments might give. For example, an initial discussion of depression's biological basis can mollify much of the angst about submitting to therapy.
Another effective tactic is to focus first on altering depression-ling behaviors, such as substance abuse, which is twice as common among depressed men as women. Most depressed men can admit --- at least to themselves --- the debilitating effect drug and alcohol abuse have. And it's often easier at first --- and more productive --- to plot a step-by-step strategy for overcoming such habits than to explore the deeper issues that initially drove us to them.
All this assumes, however, that we're even willing to seek treatment and that our therapists take an approach that doesn't push us away. "Depression is bad enough without having to deal with a doctor who treats you like your some sick helpless patient," says Pollack. "You should interview multiple people. And if they're arrogant or huffy, you shouldn't hesitate to leave and find someone else."
Just as long as you don't leave and head straight for Larry's Lounge.
END
Although new antidepressants influence the same chemical interactions in the brain that older drugs do, pharmaceutical manufacturers have had great success in reducing the legions of side effects that plague the pre-Prozac medications. And Prozac's descendents have cut reports of sexual-dysfunction by more than half, while also alleviating sleep-related problems. Meanwhile, the market's $9 billion in annual revenues continues to spur drugmakers to create antidepressants with even fewer side effects.
PROZAC -- The first of the selective serotonin uptake inhibitors (SSRIs), Prozac was introduced in 1988 and soon became the most prescribed antidepressant in the world. It’s active ingredient, fluoxetine, blocks nerve cells from recapturing serotonin and removing it from the brain.
Upsides: one pill a day brings relief not only from depression, but also from panic attacks, obsessive/compulsive disorder, and bulemia.
Downsides: In additon to the sexual dysfunctions reported by up to 50% of users, SSRIs can also disrupt sleep. Other side effects can include nausea, nervousness, insomnia, diarrhea, and tremors.
ZOLOFT -- Introduced in 1991, this SSRI is highly similar to Prozac.
Upsides: See Prozac.
Downsides: In addition to sexual side effects and sleep disruption, Zoloft has been blamed for nausea, diarrhea, dry mouth, insomnia, drowsiness, dizziness, tremors, excessive sweating, and indigestion.
PAXIL -- An SSRI introduced in 1992, Paxil is also highly similar to Prozac.
Upsides: See Prozac.
Downsides: In addition to sexual side effects and sleep disruption, Zoloft has been blamed for nausea, constipation, weakness, diarrhea, dry mouth, insomnia, drowsiness, dizziness, tremors, and excessive sweating.
SERZONE -- Approved in 1995, this is one of the newest antidepressants available. Its active ingredient, nefazadone, interferes with the removal of serotonin and norepinephrine from the brain.
Upsides: Unlike SSRIs, Serzone cuases few sexual side effects and doesn't induce sleep problems; in fact, it increases REM speed. In addition to treating depression, it also helps counteract anxiety. And because it affects both serotonin and norepinephrine, some people find it more effective than SSRIs.
Downsides: Serzone needs to be taken twice daily. Its side effects can include dry mouth, drowsiness, nausea, dizziness, constipation, weakness, lightheadedness, blurred vision, and confusion.
WELLBUTRIN -- Brought to market in 1995, Wellbutrin, whose active ingredient is bupropion, inhibits serotonin and norepinephrine uptake and also affects another neurotransmitter, dopamine.
Upsides: Few sexual side effects have been reported. It's also an effective aid to quitting smoking.
Downsides: It needs to be taken twice or three times a day and can cause substantial drowsiness --- enough to impair motor skills. Other side effects can include loss of appetite (which lead to weight loss), agitation, dry mouth, constipation, excessive sweating, dizziness, tremors, and blurred vision.
EFFEXOR -- Aprroved in 1993, this drug --- whose active ingredient is venlafaxine -- inhibits the uptake of serotonin, norepinephrine, and to a less extent, dopamine.
Upsides: Although Effexor can cause sexual side effects, ejaculation problems are reported by only 12 percent of male users and impotence by a mere 6 percent. And because the drug affects both serotonin and norepinephrine, it can be more powerful --- and act faster -- than SSRIs.
Downsides: Must be taken with feed and requires two to three dosages daily. In addition to sexual side effects, it can induce nausea, drowsiness, dry mouth, dizziness, constipation, weakness, nervousness, excessive sweating, tremors, and blurred vision.
NARDIL and PARNATE -- Older antidepressants that have become less popular because oftheir side effects, these drugs interfere with the enzyme monoamine oxidase (MAO), which helps clear serotonin, epinephrine and noepinephrine from nerve-cell synapses.
Upsides: In some cases, it's the only drug that works.
Downsides: A dangerous spike in blood pressure can result from taking MAO inhibitors with such foods as cheese, salami, red wine, avocados, bananas, chocolate, and beer. Other side effects can include dizziness, headaches, tremors, muscle twitching, confusion, memory impairment, anxiety, insomnia, weakness, drowsiness, chills, blurred vision, and heart palpitations.
ST. JOHN'S WORT -- This flowering plant has been used in traditional European medicine for centuries, primarily for wound-healing. German scientists have proved that it's a natural MAO inhibitor.
Upsides: It costs only about $10 a month and can be obtained over-the-counter. Furthermore, it doesn't appear to cause the large number of side effects that other MAO inhibitors do.
Downsides: MAO inhibitors have largely been replaced by new drugs that are more powerful, and St.-John's-wort is considered effective only for mild to moderate depression. Side effects can include dry mouth, fatigue, dizziness, rashes, and itching.
END