Prozac — and the Next Generation

Dr. Ray

‘I don’t want to talk, I just want a prescription for Prozac,’ was the first thing a new patient voiced as soon as I walked into the examining room. I looked at the chart handed to me by the nurse. Marjorie, a 42 year old graphic artist, married with one child, a twelve year old daughter. She continued, ‘I’ve read Dr. Kramer’s Listening to Prozac and I know that Prozac is what I need.’

She looked so tense, her upper and lower jaws almost grinding her teeth. Stern-faced, she was menacing. I sat down and tried to elicit a medical and psychological history. Her answers were brief and almost rude. She did not have any past medical or mental problems. Her job was stressful, a boss repeatedly pressured her to have projects ready by unreasonable deadlines, and she was having constant arguments with her husband. She was not in the least interested in discussing any cognitive or behavioral psychotherapeutic options as treatment. After a physical exam including a neurological check-up, and making sure that she did not have any suicidal or homicidal ideations, I started her on 10 mg of Prozac and prescribed 21 pills.

Three weeks later she was back in the office. I apprehensively walked in the room expecting the stern face. ‘Hello Doctor, how’s your day going?’ She said flashing a smile. I looked at the chart to make sure she was really Marjorie. ‘You seem so different’ I blurted. She nodded, ‘I feel calmer than I have for years.’

Millions of Americans are using mood-altering prescription medicines. What is so different about Prozac? Before we answer this question let’s go over the basics about the brain and neurotransmitters.

We each have over 100 billion neurons (brain cells) that communicate with each other electrically and chemically. The junction where one neuron touches to

communicate with another neuron is called a synapse. A synapse is a little space where one neuron releases a chemical which then crosses the space and attaches to a receptor on the other neuron. The chemicals the brain uses to communicate with are called neurotransmitters. At present at least 60 of them have been identified. Some of them are serotonin, norepinephrine, dopamine, endorphin, acetylcholine, phenylethylamine, etc.

Our moods are associated with the levels and balance of these neurotransmitters. Low levels of serotonin are implicated in depression, alcohol abuse, bulimia nervosa, obsessive-compulsive disorder, and more. Prozac and its cousins Zoloft and Paxil are called selective serotonin reuptake inhibitors (SSRI). (The word selective is used since they primarily raise serotonin levels as opposed to dopamine or norepinephrine.) They prevent serotonin in the synaptic cleft from being broken down, thus increasing the amount and time serotonin has to act on the receptor.

Before the SSRI came on the market other effective anti-depressants, such as imipramine, were available. They also elevated serotonin levels but at a cost. They influenced many other receptors in the brain that were not involved with mood. Stimulation of receptors such as cholinergic, histaminergic, and adrenergic resulted in many unpleasant side effects thus limiting the use of these medicines to those who were seriously depressed. The SSRI have opened a new chapter in psychopharmacology. Now even those who are mildly depressed may use these medicines for mood enhancement without paying the piper.

The SSRI are not totally free of side effects. In higher doses they can cause nausea, dry mouth, impotence, insomnia, and rash. A few years ago there was a media scare about higher rates of suicide

in those who had started taking Prozac. Careful studies disproved these claims$^{1}$. It turns out Prozac does not lead to any more frequent cases of suicide than does placebo or other anti-depressants. However, we don’t know the long-term effects of these medicines. There are receptors for serotonin not only in our brain, but on certain cells of our immune system such as white blood cells. As of yet we do not know if taking SSRI for prolonged periods will enhance, interfere or have little effect on our immune system.

Any form of therapy can have side effects. Sometimes we overlook the fact that a natural treatment, such as psychotherapy, can also have side effects if the therapist is not competent. On occasion, a patient may get even more depressed if many repressed traumatic emotions are exposed too quickly. There have been many cases of suicide in those undergoing psychotherapy. There have also been many cases of suicide in those who were depressed but did not seek therapy. The benefits of treatment versus the possibility of side effects must be carefully weighed. Each person is unique and requires a unique approach to treatment.

EXTROPY #14 (7:1) First Quarter 1995

36

Many psychiatrists are using medicines and psychotherapy synergistically, reducing the time it takes to improve a patient’s mood.

The discovery of these new medicines and their low side effect profile has grayed the black or white way of thinking about and treating depression. Many people are beginning to accept the possibility that mood-enhancing medicines can be used effectively not only in the severely depressed, but also in those who are mildly depressed. Mild personality trait weaknesses such as low self-esteem are being successfully treated. Not only does our personality influence our moods, but our moods can in turn influence our personality. Recently, some people are raising the possibility that even relatively content individuals can take these medicines to become even happier.

Let’s discuss each SSRI presently available with a few words about new ones that may be introduced to the American market over the next few years. Since we don’t know the long-term effects of these medicines, it’s advisable to use the lowest effective dose and to slowly taper them and stop after a few weeks or months. They can always be restarted again if necessary.

Prozac (fluoxetine) was introduced in 1988. Since then millions of prescriptions have been filled, making the stock owners of Eli Lilly quite a jovial bunch. In March 1994 the FDA approved Prozac for the additional use in treating obsessive-compulsive disorder (OCD). Prozac is available as 10 and 20 mg capsules and liquid solution of 20 mg per teaspoon.

Zoloft (sertraline) was introduced in 1991 and is available as 50 and 100 mg tablets. In a recent small trial of 11 patients treated with Zoloft for social phobia, 7 improved.$^{2}$

Paxil (paroxetine) was introduced in 1992 and comes in 20 and 30 mg tablets.

Luvox (fluvoxamine) is expected to receive FDA approval soon. It has been available in foreign countries for the past 11 years. It will likely be used for obsessive-compulsive disorder (OCD). Compulsive sexual exhibitionism has been successfully treated with Luvox. Some psychiatrists now believe that exhibitionism may be an OCD.$^{3}$

Femoxetine is in the process of being approved but is not yet available.

In February of 1994 a new medicine became available called Effexor (venlafaxine). It raises both serotonin and norepinephrine levels and is believed to work faster as an antidepressant. Tablets come in 25 mg and 50 mg.

The many faces of serotonin receptors

In the last few years, neuroscientists have discovered that there are many types of serotonin receptors. They have started numbering them 1A, 1B, 1C, 1D, 2A, 2B, 3, 4, etc. Serotonin acting on each receptor will have a different effect. Furthermore, neurons in different parts of the brain have different serotonin receptors. Using this information, neuropharmacologists have developed different types of drugs that are much more specific.

Buspar (buspirone) was approved by the FDA in 1986. It acts on serotonin receptor type 1A as an agonist. The word agonist as used in pharmacology means that the drug stimulates the receptor. Antagonists do the opposite: they block the receptor and in the case of serotonin receptors, an antagonist will not allow serotonin to act on that particular receptor. Buspar is used to relieve anxiety, and unlike diazepam (Valium) and other benzodiazepines, it has no sedative or euphoric effects and has no withdrawal symptoms.$^{4}$

LSD (lysergic acid diethylamide) is of course not a new discovery, but I mention it here because researchers now suspect that it acts on serotonin type 2 receptors in its hallucinogenic effects. Interestingly, some newer anti-psychotics drugs such as risperidone and clozapine, used in schizophrenia, partly work by blocking type 2 receptors. They are antagonists. There is a possibility that they can be used to stop a bad acid trip. Over stimulation of type 2 receptors have been implicated as one of the causes of schizophrenia.

Ondasetron is marketed as an anti-nausea medicine and used to prevent vomiting in cancer patients who are receiving chemotherapy. It is a type 3 antagonist.

Over the next few years more specific

serotonin receptor agonists and antagonists will be found and marketed. A recent survey showed that within the next six years 31 medications—16 for mood disorders, 15 for anxiety disorders—will be available to the public.$^{5}$ This is likely to give doctors ever more refined tools to help patients suffering from depression, anxiety, and various other illnesses. Perhaps more research will be done in combining medicines with other forms of non-drug therapy to maximize synergism. Psychiatrists are additionally studying the possibility of using low doses of two or more drugs as a more effective approach. For instance a SSRI can be used to elevate serotonin while another anti-depressant can be used that elevates dopamine, norepinephrine, and others.

Back to Marjorie. During her second visit she reported having slight insomnia and mild nausea off and on. You recall she was on 10 mg of Prozac a day. I lowered her dose to 5 mg a day, in the liquid form. She returned a month later indicating that she was still getting benefits from the medicine with few if any side effects. Her relationship with her husband had improved. The stress at work was still there, but it was more tolerable. She continued on Prozac for another three months and then I gradually tapered her off the drug. I saw her a month after her last dose and she reported that the calmness she had experienced on Prozac had partly faded away but she had incorporated some new coping skills. During previous visits I had discussed with her stress reduction techniques including meditation, exercise, change of attitude, and improved nutrition. She preferred to wait and see and continue trying exercise, a better diet and other natural methods before restarting Prozac. ‘I feel comforted to know that a medicine is there for me in case I ever need it again.’

1. Beasley et al; Fluoxetine and suicide. Br Med J 303:685-692, 1991.

2. Psychiatric Times, July 1994, p15.

3. Zohar et al: Compulsive exhibitionism successfully treated with fluvoxamine. J Clin Psych 1994; 55:86-88.

4. Buspirone: Seven-year update. J Clin Psych, May 1994.

5. Psychiatric Times. July 1994, p44.

Also see The Psychiatric Clinics of North America: Annual of Drug Therapy, volume 1. 1994.

37

EXTROPY #14 (7:1) First Quarter 1995

ADVERTISEMENT

Propagate happy and loving ripples that grow, spread… and return, begins Dr Ray in his groundbreaking new book,

Be Happier Starting Now.

This unique creation brings together knowledge and wisdom from psychology, neurochemistry, personal growth, nutrition, philosophy, sociology, medicine, and more — a truly complete and eclectic mind-body approach to a healthy and happy life.

Written in a gentle, poetic style, every page of Be Happier Starting Now will make you think — and feel. It has already touched and warmed many hearts. It will touch yours too.

Dr Ray writes with an inspirational and compassionate style to illustrate the beauty and charm of that most universal of human quests… Happiness. And not just for ourselves, but for everyone with whom our lives are intertwined. Read the book and start living a life beyond “ordinary”.

What is the secret to Happiness?

This unique book boldly takes on the challenge to reveal answers to a question that has puzzled humanity for millennia. It is possible to be happier. All that is required is knowledge and the self-guidance to follow through. The secret to happiness is that there are many secrets. Practical steps and tips are provided in the following ten chapters.

1. Developing a Healthy Personality.
2. Cultivating a Sense of Connection.
3. Healing the Wounds.
4. Setting Goals to Follow Our Dreams.
5. Finding Satisfying Work.
6. Having Financial Security.
7. Pursuing Pleasure… Intelligently.
8. Nurturing Physical and Mental Health.
9. Learning and Creating.
10. Developing a Personal Truth.

The first few pages of the book provide a philosophical and scientific overview including a discussion of The Brain: an owner’s guide. The appendix is comprised of the following four sections:

The mind-body two-way communication.

Natural mood-enhancing substances.

Mood-enhancing medicines.

The one-minute happiness test.

An extensive Notes and References that includes the latest research is also provided.

Be Happier Starting Now: A Medical Doctor Explores the Fascinating Field of Happiness is one of the most well thought out and inspiring self-help books ever published. Yet, it is friendly science, friendly philosophy, compassionate, and unabashedly poetic.

Dr Ray is certified by the American Board of Family Practice. He has observed human nature in tens of thousands of personal and professional experiences. He wishes to share with you his “it really works” approach to a healthy and happy life.

Be happier and live longer.

Please send $14 (includes tax and shipping) to:

Be Happier Press

PO Box 12619

Marina Del Rey, CA 90295

Please indicate whether you wish the author to sign your book. 208pp. ISBN 0-9639755-0 6x9 inches

EXTROPY #14 (7:1) First Quarter 1995

38