New Generation of Medications Aids in Psychotherapy

About one-quarter of the hospital beds in the United States are occupied by patients with a mental illness, more than heart disease, cancer and respiratory illness combined. If that figure seems very high, compare it to the mid-1950s when over half of U.S. hospital beds were occupied by persons with mental illness, mostly schizophrenia.

In 1955, by accident, a new medication developed to treat tuberculosis was found to also elevate mood in depressed patients. Unfortunately, the medication (a monoamine oxidase inhibitor, or MAOI) had the potential of causing liver problems, hypertension and could be toxic if certain foods - cheeses and aged foods - were eaten. Concurrently, a group of drugs called phenothiazine drugs were being developed as antihistamines, but were found - again, by accident - to be very useful in the treatment of psychoses such as schizophrenia. By the end of the 1950s, hundreds of thousands of patients were discharged from U.S. hospitals because of these new drugs. (The phenothi-azines were shown to cause neurological side effects over time.)

Forty years later, the MAOI drugs and the phenothiazines are rarely prescribed. But their discovery ushered in the modern era of psychopharmacology - the treatment of psychiatric illnesses with medications - and the real possibility for mentally ill people to live more "normal" lives than ever before imagined. In the 1960s newer generations of medications were developed for depression, bipolar disorder, anxiety and the psychoses. The tricyclic antidepressants (so called because of their chemical structure) were originally developed as anti-psychotic agents; they had little effect on schizophrenia, catatonia or paranoia but greatly alleviated symptoms of major depression. Several tricyclics are still in use today and - though caution must be used because of side effects - they are highly effective in the treatment of many patients' depression.

Broadly speaking, there are four major classes of psychopharmaceuticals: antidepressants, largely used for depression; antipsychotics, used in major psychiatric disorders such as schizophrenia and paranoia; anxio-lytics, used for anxiety disorders; and mood stabilizers, used in bipolar or manic-depressive illness.

"Life has its ups and downs, and its major hurdles," says Dr. Lauren B. Marangell, director of the Mood Disorders Center and assistant professor of psychiatry and behavioral sciences at Baylor College of Medicine. "Medications treat brain-based disorders. They are biochemical agents. For the person experiencing a divorce, a pill won't change the hurt of that divorce. Now, if a situation creates a lingering depression, that may need to be treated."

Dr. Marangell cautions against "knee-jerk psychopharmacology," or the over-prescribing of medications, but she recognizes the importance of continued drug development. "It was a milestone in 1987 when Prozac was introduced," she says.

"Prozac® - fluoxetine - and similar medications in this class are called anti-depressants, but they work for a whole host of other illnesses," says Dr. Alan C. Swann, professor in the department of psychiatry and behavioral sciences at The University of Texas-Houston Medical School. "These are conditions that have different causes but can be helped by the increase of serotonin at the nerve receptors in the brain." Prozac and the newer medications closely related to it - paroxetine, marketed under the name Paxil, and sertraline, sold as Zoloft, are probably the two most well-known - are called SSRIs, or selective serotonin reuptake inhibitors, because of what they do in the brain's chemistry.

Serotonin is the best known of the 50 or 60 neurotransmitter chemicals in the brain. (It also stimulates nerves in the gastrointestinal tract.) Neurotransmitters are chemical molecules that are released by neurons in the brain and stimulate neighboring neurons, creating electrical signals which become emotions and thoughts. For example, upon hearing the loud growl of a dog, one neuron releases serotonin into the synapse, or vacant space, near the closest neighboring neuron (called a receptor). The serotonin stimulates an electrical response that continues until a thought is formed - in this case, fear of a possible attack by the dog.

"We have known that serotonin is a neurotransmitter with an interesting role in behavior," says Dr. Swann. "It was shown in the 1960s that medications which decreased serotonin and another important neurotransmitter called norepinephrine in the brain brought about an increased depression. Subsequently, it was shown that the tricyclic antidepressants worked because they inhibit the re-uptake, or absorption, of serotonin. In other words, more serotonin was left in the synapses to keep stimulating the receptor neurons, and this action makes people feel better."

Prozac coming into the marketplace in 1987 was a milestone for several reasons. The SSRI (or serotonin enhancing) antidepressants have fewer side effects than the older tricyclic antidepressants. The SSRIs are not lethal in large doses, and in a depressed patient overdosing is always a concern. SSRIs are usually taken in a single daily dose, so compliance with the medication is easier. Finally, though SSRIs were developed as antidepressants, they have been shown to be highly useful in treating panic disorder, the eating disorder bulima, post-traumatic stress disorder, social phobia, migraine headaches, autism, and pre-menstrual syndrome. Importantly, they are effective in treating dysthymia, a common "low-grade" form of depression. "Depression and anxiety frequently go together, so the SSRIs are very effective for these patients," says Dr. Swann.

Just 10 years after the first SSRIs came onto the market, these medications are now the most-prescribed of all drugs, each of them generating billions of dollars in sales. In the U. S., there are millions of new prescriptions written for them each month. Prozac is probably the most often cited medication in cartoons, and has nearly become a part of our daily language in the same sense that "tranquilizer" has.

"A physician will prescribe medication after talking with the patient," says Dr. Marangell. "The known side effects of the medication have to be looked at, and the patient's lifestyle has to be taken into consideration. The SSRIs are very positive in both of these areas." Because the SSRIs are so effective and well-tolerated, they are readily prescribed by family physicians. "That's appropriate," says Dr. Marangell. "Remember, fully half of the depressed people are not seeing a physician for their depression, much less becoming involved in psychotherapy."

But some question the possible overuse of psychoactive medications, particularly the SSRIs. Stories in weekly newsmagazines have portrayed people taking the SSRIs simply to go to "another level" of productivity and enhanced mood, of people with mild discontent or a passing case of "the blues" taking the medications rather than examining what is at the root of their problem. Still other people who have taken the SSRIs say the drugs give a "false sense of security" and mask what are the normal "ups and downs" of life.

"Every age has its stresses," says Dr. Swann. "We look to specific therapies for specific problems. New and interesting medications in development now will target other neurotransmitters, following the thought that there may be serotonin-based depression and norepinephrine-based depression. The newer drugs will be `cleaner' acting, probably with fewer side effects.

"There will continue to be people who are desperately in need," says Dr. Swann. "If treated with the right medication, they'll be able to support themselves in other ways. The brain will work better in their environment."

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©2006 Texas Medical Center

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