Better Living Through Chemistry
Recognizing the value of the newer antidepressant medications is the next step in the evolution of treatment for depression.
Theories about depression existed long before Freud or pharmacology. Hippocrates insisted that mental disorders had organic causes, with melancholia brought on by an excess of black bile from the spleen. In the early seventh century devil-possession was accepted as the reason for deviant behavior. Clerics would check depressed people for marks on the skin that could have been made by Satan and cures involved placing holy relics on the afflicted.
These days, many people view depression as an emotional weakness. Women suffering from depression are often characterized as “moody.”
In reality, people with depression often have an imbalance in the brain of certain chemicals called neurotransmitters—specifically serotonin and norepinephrine, according to Glen Stimmel, Pharm.D., professor of clinical pharmacy, psychiatry and the behavioral sciences, USC School of Pharmacy and Keck School of Medicine of USC. This imbalance, he says causes symptoms including a persistent sad or empty mood, feelings of hopelessness and guilt, loss of interest in pleasurable activities, decreased energy or fatigue, oversleeping or insomnia, changes in weight, anxiety and thoughts of death or suicide.
Because depression has real, physiological roots in the brain, scientists have been able to design effective treatments for it, Stimmel says. A number of new drugs are helping people overcome this debilitating disease and lead healthy and productive lives. But without more public education about depression and its destructive ways, the illness will continue to claim more victims.
Major depression is the leading cause of disability and affects about 10 million adults, ages 18 and older, each year, according to the National Institute of Mental Health (NIMH). Nearly twice as many women as men suffer from depression, with the average age of onset in the mid-20s. The NIMH estimates that 15 percent of people suffering from major depression commit suicide.
For some people, major depression can be a chronic illness recurring throughout their lifetime. Studies suggest genetic links to depression, yet stressful life events may play a significant role in triggering the disease. Hormonal changes in women are also thought to act as a provoker of symptoms, often during pregnancy or postpartum.
Antidepressant drug therapy has become a key component in the treatment of depression, yet two-thirds of those affected by the disease do not get the help they need.
“A diagnosis of depression in a primary care setting continues to be under-recognized, and when diagnosed, is often inadequately treated,” Stimmel says.
Stimmel, who has written extensively about depression, says many patients suffering from the disease do not get sufficient treatment. Due to managed health care, most depressed patients are treated exclusively by a primary care physician instead of seeking help from a psychiatrist, which contributes to missed diagnoses and inadequate treatment.
“Primary care physicians don’t always have enough time with a patient and may not ask the right questions in order to diagnose depression correctly,” says George Simpson, M.D., professor and interim chair of the Keck School’s Department of Psychiatry and the Behavioral Sciences. “Patients may be afraid to discuss symptoms of depression and may be embarrassed about the stigma associated with the disease.”
Primary care physicians are trained to focus on physical complaints to rule out medical conditions such as diabetes and thyroid disorders, which are often characterized by symptoms of depression. This is especially problematic for senior citizens with symptoms of fatigue or dementia, which are two of the major warning signs for depression in that age group.
“Some physicians associate memory impairment or lack of energy solely with old age, when in reality, the senior citizen may be depressed,” Simpson says.
Restoring the balance
Along with a proper diagnosis, successful treatment of patients with depression requires careful monitoring and fine tuning of antidepressant medication over time, Stimmel says. No two people will respond to an antidepressant in the same way. A physician may have to alter the dosage or change the type of drug altogether to achieve favorable results.
Antidepressants work by restoring the balance of neurotransmitters to normal levels in the brain, creating a domino effect that alleviates depression symptoms, says Stimmel, who adds that, in recent years, there have been major advances in antidepressant medications.
The evolution of antidepressants and the way they work can be conceptualized as an hourglass, Stimmel says. At the wide top portion of the hourglass are the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which were discovered more than 40 years ago. Both of these drug classes enhance levels of serotonin and norepinephrine in brain and are proven to treat major depression.
Stimmel says patients need to carefully follow a physician’s directions with these drugs because they pose a high risk of drug interactions and side effects, which include dizziness, drowsiness, blurred vision, headache, nausea, weight gain and an increased risk for arrhythmias (rapid heartbeat) and other heart problems. The drugs can also cause problems if taken with other prescribed or over-the-counter medications.
Prozac nation
The narrow mid-portion of Stimmel’s hourglass model is represented by the selective serotonin reuptake inhibitors (SSRIs), which help restore serotonin levels in the brain. Even though these drugs have no effect on norepinephrine—the other key neurotransmitter—they are successful in alleviating depressive symptoms.
SSRIs took the pharmaceutical industry by storm with the advent of Prozac and its cousins Paxil, Zoloft, Luvox and Celexa. Because they are safe and easy to use, these antidepressants have become the most highly prescribed psychotropic drugs of their kind.
“The SSRIs do not possess most of the significant adverse effects seen with the TCAs, and they offer a much greater safety from overdose,” Stimmel says. “But, there is evidence that SSRIs may be less effective in achieving full remission of symptoms.”
Although TCAs may be more effective, clinical trials show that more patients remain on SSRIs longer because they are more easily tolerated, Stimmel says.
Not without risk of drug interactions, some SSRIs (Prozac, Paxil and Zoloft) interact with liver enzymes that metabolize certain medications, altering the drugs’ effectiveness in the body. According to Simpson, these harmful drug interactions are simple to avoid with the help of an experienced physician.
Celexa does not have the same drug interaction potential as some of the other SSRIs, which makes it increasingly popular in the senior citizen population. “For senior citizens, I often choose Celexa because there
are fewer potential interactions with other
prescription drugs,” Simpson says. “When choosing an SSRI, I think of potential side effects, since the drugs work the same way.”
Although slightly different with each SSRI, potential side effects include dizziness, drowsiness, nausea, dry mouth, constipation, headache, stomach upset, insomnia and sexual dysfunction.
Sex and side effects
“A major drawback to using SSRIs is that one third of patients will experience nausea and problems with delayed orgasm or ejaculation,” Stimmel says. “These patients are often reluctant to discuss sexual side effects with their physician, and as a result, may discontinue use of the drug prematurely.”
In keeping with the model, the broad lower portion of the hourglass represents the newest antidepressants, such as Effexor, Remeron and Wellbutrin. Remeron is unique because it decreases the risk of sexual side effects and nausea, Stimmel says. These drugs target serotonin and norepinephrine neurotransmitters just like the older TCAs, without the severe side effects. Data suggests that these antidepressants may be the most effective to date.
“In comparison to SSRIs, antidepressants that target both serotonin and norepinephrine may offer enhanced remission of symptoms in major depression,” Stimmel says. “Recognizing the value of these newer antidepressants is the next step in the evolution of treatment.”
Antidepressant drug therapy must be taken for at least two to six weeks before most people see a noticeable change, according to Stimmel. The prescribed dose must be taken every day for it to work. After the depressive symptoms subside, patients need to keep taking the drugs for a total of six to 12 months.
“Without medication, an episode of depression lasts approximately six to 12 months,” Stimmel says. “An antidepressant brings the balance of neurotransmitters back to normal levels right away, decreasing the suffering of the patient. Continuing drug therapy for the length of a normal depressive episode can prevent recurrence of symptoms.”
He explains that side effects are common when a patient first begins treatment and are usually dose-dependent (the higher the dose, the greater possibility of side effects). As the body gets used to the drug, many side effects will either subside or decrease in severity.
“Patients need to understand the side effects of antidepressants so they know what to expect,” says Michael Wincor, Pharm.D., associate professor and interim chair of the Department of Pharmacy at the USC School of Pharmacy. “It is crucial for depressed individuals to have faith that they will feel better in six weeks—and that experiencing side effects means that the drug is working.”
Natural lift
For those people seeking a “natural” remedy for depression, a popular—albeit controversial—herbal supplement is available at health food stores and pharmacies without a prescription.
Some people believe that St. John’s wort, a derivative of a bright, yellow blossom that blooms in the spring, acts like an antidepressant in the brain, yet scientists are not sure how, and some are not willing to say that the herb works at all. They are also unsure of potential side effects and drug interactions and warn that St. John’s wort can be extremely dangerous for people taking prescription medications. St. John’s wort may reduce the effectiveness of cholesterol-lowering drugs, oral contraceptives and AIDS medications. There also is a concern that this herb can trigger rejection and loss of a transplanted organ by interfering with the drug cyclosporin.
Another problem stems from how St. John’s wort is manufactured, since the U.S. Food and Drug Administration (FDA) does not monitor the production of herbal supplements, Wincor says. “There are no industry standards for herbals and no regulations for manufacturing St. John’s wort. Buyers cannot be sure how much of the active ingredient is in the pills they are taking.”
According to Wincor, several of the clinical studies of St. John’s wort have been poorly designed and not well controlled. The National Center for Complementary and Alternative Medicine is currently funding a new study coordinated at Duke University, which may give health care professionals better answers about the effectiveness and safety of the supplement.
“Overall, it seems that St. John’s wort may work for mild to moderate depression for those who insist on a natural approach,” Wincor says. “But it does not appear to be an appropriate therapy for individuals with severe major depression.”
Road to recovery
Regardless of treatment options, clinicians agree that the first crucial step towards recovery is recognition of depressive symptoms—and acknowledgement that depression is a serious, medical condition that must be treated by a physician.
“Many patients are hesitant to discuss feelings of depression with their physician since [they believe] that would require an admission of emotional weakness,” Stimmel says. “Other patients are uninformed about depression, believing that their symptoms are a natural part of life.”
With proper treatment, a depressed patient stands an 80 to 90 percent chance of achieving complete recovery, according to the National Institutes of Health. Despite advances in antidepressant medications, patient education remains an obstacle in the treatment of the disease.
“One-third of patients discontinue antidepressant use within the first month of treatment, and only 40 percent remain on the medication for the full length of time,” Stimmel says.
Some patients worry, he says, that antidepressants are addictive or think that they are stimulants like cocaine or amphetamines. Stimmel emphasizes that the patient must understand that this is not the case with antidepressants; they work by restoring normal functioning of neurotransmitters. Others do not understand how the drugs work and the length of time they need to remain on them. Some patients mistakenly believe that if they feel better, they should stop taking the medication.
“Physicians and pharmacists need to explain to patients how antidepressants work and communicate what side effects to expect,” he says.
Along with the advanced treatments for depression, better communication between patient and physician will help bring a diagnosis of depression out of the dark ages.
Says Stimmel, “Clinicians can help their patients recover from depression by investing time in education, by understanding the perspective of the patient and by negotiating treatment options.”
For more information about the research and treatment of depression, or to learn more about The Doctors of USC, call 1-800-USC-CARE (1-800-872-2273).
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