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Introduction
Antidepressant medications are among the most widely prescribed medications in the world. This is because they are helpful to so many people. Antidepressant medications are medically safe, and they are non-addictive¾and most modern antidepressants are without troublesome side-effects.

Antidepressants are used for many purposes. They were first used to treat clinical depression¾hence their name. Over the years, however, they have been found to be useful in treating other conditions besides depression. They help reduce anxiety and nervousness, for example. They can also reduce chronic pain, and they can treat insomnia without addictive worries. They can stop bed-wetting in children; and one of them is even used in treating obesity. Three of the antidepressants are used sometimes in treating Attention Deficit Disorder (A.D.D.). Antidepressants are used to stop obsessive-compulsive symptoms and can be used to reduce excess anger.

Clinical depression, though, is by far the most common reason that antidepressants are prescribed.

Other reports at our office describe clinical depression, anxiety, Alzheimers and A.D.D. Please review those reports for specific information about the symptoms, causes, and treatments of those conditions.

General Comments
Before going into specific information about each major type of antidepressant, some comments regarding all antidepressants will be useful.

1. All of the antidepressants work by increasing the amounts of naturally occurring “neurotransmitters.” These are small molecules that the brain uses to “run” its various circuits. Levels of neurotransmitters that are too low can cause a variety of symptoms.

2. It usually takes two to four weeks for symptoms to begin to improve after an antidepressant is prescribed. The antidepressants are not “uppers;” they should not make you “high,” but you should experience normal emotions, without being as down or nervous.

3. None of the antidepressants are addictive or habit-forming. However, it is best not to stop them suddenly. Most persons feel better if their antidepressants are tapered down when the time comes to stop the medicine.

4. With some exceptions, antidepressant medication treatment needs to be continued at least nine months. If the symptoms for which the antidepressant are prescribed had been present for more than six months, or had recurred over several years, then the duration of antidepressant treatment should be longer than nine months.

5. In general, antidepressant medications should be started at a lower dose, then increased over at least a couple of weeks. By starting at a lower dose, most side effects can usually be totally avoided.

6. To know whether a particular antidepressant will work for a person requires at least a four-week trial. After four weeks, if there is no improvement, a different antidepressant should be tried. If there is small improvement, then an increase in dosage should be tried. If at four weeks there is considerable improvement, then the same dosage should be continued. Even at the same dose, further improvement will occur for about three months.

7. If, at four weeks, the person has only a small improvement, then augmenting medications can be added to the antidepressant. These medications usually boost the effectiveness of the antidepressant within two weeks. The most commonly used augmenting medications are: lithium, Cytomel, BuSpar, and pindolol. Sometimes, a second antidepressant is prescribed to boost the effectiveness of the first antidepressant.

8. By themselves, antidepressants are about 75% effective for most conditions for which they are indicated. When cognitive therapy (see separate report) is added to antidepressant therapy, the combination is usually about 90% effective.

9. Once an antidepressant begins to work, it usually continues to work for as long as it is taken. In a minority of patients, the antidepressant quits working for unknown reasons. When this occurs, we switch to a different antidepressant.

10. There are very few dangerous medication interactions between antidepressants and other medicines; however, it is wise to always inform each of your physicians of all medications, both prescription and over-the-counter, as well as all herbal remedies, that you use.

11. There are few side effects with most modern antidepressants; however, it is wise to consider any new symptoms that begin shortly after starting any new medication a side effect of that medication until proven otherwise. Please inform your physician of any such new symptoms that occur after you begin an antidepressant.

Specific Antidepressants
Now we will discuss each specific type of antidepressant. All of the above comments apply to each of these types.

Serotonin reuptake inhibitors: SSRIs

The SSRIs are among the most commonly prescribed antidepressants. This is because they are effective, have few side-effects, and are relatively uncomplicated to prescribe.

As the name implies, SSRIs increase the neurotransmitter “serotonin” in the brain fluid by blocking (“inhibiting”) its “reuptake” out of the brain fluid and into the storage vessels in brain cells. As the brain cells continue to release more serotonin into the brain fluid, the level of serotonin in the fluid rises.

Serotonin attaches to the outside of brain cells. This attachment activates the cell. Millions of such activated cells comprise the various circuits of the brain.

Proper functioning of serotonin seems to be crucial to the circuits in the brain that control many non-verbal brain functions: mood, tension, pain, sleep, etc. Studies have identified low levels of serotonin in the brain fluid of persons with symptoms of depression. As the SSRI increases the level of serotonin, you will notice an increased feeling of normal well-being. This should begin at about two weeks of treatment and peak at about eight weeks of treatment.

Prozac, Paxil, Zoloft, and Luvox are the best-known SSRI-type antidepressants. Celexa is a new SSRI. Serzone is also a SSRI. There have been scare stories about Prozac: that it would turn patients into murderers, or cause them to commit suicide. None of these stories are true. The FDA investigated these stories thoroughly, and concluded that they are unfounded.

The SSRIs are usually taken once-daily, in the mornings. However, they work no matter what time of day they are taken, and if they cause any drowsiness they should be taken at bedtime. Other side-effects are not common. Occasionally they will cause headache or upset stomach. Sometimes they may cause jitteriness or irritability¾this is usually relieved by lowering the dose temporarily. Some numbing of the sexual response is not uncommon, but improves with time, and can be improved sooner with other medications (even the herb Gingko biloba) if necessary. Overall, more patients feel better with fewer side-effects on SSRIs than any other type of antidepressant. That is why an SSRI antidepressant will usually be the first type tried with any patient.

Most other medications can be taken with the SSRIs without problems. A few medications should be used with caution with SSRIs, and your physician must be told that you are on both medications. These medications include: Coumadin, Theophyllin, b-blockers (propranolol, timolol, metoprolol), Dilantin, calcium channel blockers (nifedipine, diltiazam, verapamil), tranquilizers, dextromethorphan (in many cough syrups). In addition, lower doses of acetaminophen and of tylenol should be used when you are on an SSRI antidepressant. Propulsid, and some of the prescription antihistamines, should not be taken with Serzone because of possible heart damage.

Mixed Serotonin-Norepinephrine Reuptake Inhibitors

Some antidepressants increase the levels of the neurotransmitter norepinephrine, in addition to increasing serotonin. Norepinephrine is another of the three neurotransmitters that are most important for emotional health. Increasing the level of norepinephrine reduces the symptoms of depression and anxiety for most patients. These medications try to add the benefits of raising norepinephrine to the benefits of raising serotonin.

Many patients who do not fully respond to the SSRIs, do respond to these “mixed-type” antidepressants. Raising the level of norepinephrine more often produces “nuisance” side-effects than does raising serotonin alone. Therefore, we often do not try these “mixed” medications first. We will usually try them if a patient does not respond to an SSRI. Sometimes we will try a “mixed” type first if the patient has severe anxiety, severe insomnia, severe loss of appetite, or in other special circumstances.

The “mixed-type” antidepressants include: Remeron, Effexor, nortriptyline, amitriptyline, amoxapine, doxepin, imipramine. Antidepressants that mainly increase norepinephrine without increasing serotonin include desipramine and Ludiomil.

This type of antidepressant is likely to cause side effects such as: drowsiness, dry mouth, blurred vision for fine print, and weight gain. Within this class, Effexor is the least likely to cause these side-effects, and we will often use Effexor as a first-line medication.

These medications, too, begin to produce improvement in symptoms about two weeks after starting, with peak improvement at about eight weeks.

Numerous medications can increase the blood-level of these medications when they are taken together, so inform your physician of any other medications you are taking.

Dopamine-Increasing Antidepressants

The third of the neurotransmitters that regulate our emotions is dopamine. Only one antidepressant increases dopamine primarily: Wellbutrin.

In my experience, Wellbutrin is not quite as effective as the other antidepressants for reducing depression symptoms in most patients. For this reason, we do not often prescribe it first. However, Wellbutrin is uniquely useful in certain situations.

First, when a patient does not improve with the SSRI or mixed-type antidepressants, she may well respond to Wellbutrin. Secondly, when a patient has ADD in addition to depression, Wellbutrin can sometimes treat both conditions with one medication (a deficit of dopamine seems to be the problem in ADD). Thirdly, when a patient has depression symptoms of over-sleeping, extreme fatigue, and over-eating, Wellbutrin can often reverse these symptoms faster than other antidepressants.

The most common side-effects of Wellbutrin include: tension, nervousness, irritability, insomnia, and weight loss. Loss of desire for cigarettes is a common side-effect of Wellbutrin; as a matter of fact, Wellbutrin is also marketed as Zyban, to help stop smoking.

Wellbutrin has very few interactions with other medications. Nevertheless, tell your physician that you are on Wellbutrin. Many patients find that they need to reduce their intake of caffeine while on Wellbutrin. Some patients with a seizure disorder should not take Wellbutrin.

Conclusions

The discovery and development of the antidepressants is truly one of the miracles of medicine. They are as important to health as are the antibiotics. They can reduce excessive emotional suffering, improve career performance, and improve relationships. They can improve self-esteem.

The greatest limitations to the wide-spread benefits of antidepressants are fear and lack of knowledge. Many persons believe these medications are addictive, or that they will produce a false “high,” or that using them means a person is “weak” or has little “will-power.” None of these beliefs are true; just as they are not true for penicillin or high blood pressure medications.

Most health insurance will reimburse 50% to 80% of our fee. By the way, a recent health insurance audit showed our costs of care to be 35% less than similar specialists in Arkansas. I believe this is because we are dedicated to fast, accurate diagnosis and quickly effective care.