Researchers are not sure how any antidepressant works. However, it is believed that the first step in most commonly used antidepressants is to influence the way in which nerve signals are transmitted from one neuron to another.

This transmission occurs when chemicals called neurotransmitters are released from vesicles in the transmitting neuron. After they have communicated the message the neurotransmitters are taken back up by the transmitting neuron. They are then broken down by the enzyme monoamine oxidase, or MAO.

Most antidepressants seem to inhibit the re-uptake of the neurotransmitter, a step that is thought to be the initial action that leads to the reversal of they symptoms of depression. By blocking the re-uptake of these neurotransmitters, the antidepressants allow the neurotransmitter chemicals to remain in the synaptic cleft where it can exert its effect longer, which may be the catalyst in the over-all treatment of depression.

There are three neurotransmitters - serotonin, norepinephrine and dopamine. Serotonin is believed to be responsible for feelings of satisfaction and contentment while norepinephrine controls alertness and activation and dopamine mediates social interactions. All of these can be effected in people with depression. Thus, different medications differ by which neurotransmitters inhibit the re-uptake of. These differences affect their side effect profiles and their therapeutic effects as well.

Older tricyclic antidepressants affect many different types of receptors, including those that have nothing to do with depression, which caused several undesirable side effects. Prozac and Zoloft are forms of SSRIs, which affect serotonin re-uptake without affecting other neurotransmitters to any great extent. Another type that is commonly used in the United States is bupropion, or Wellbutrin. This antidepressant is thought to act more selectively on dopamine and norepinephrine. MAO inhibitors, like Nardil or Parnate, work by inhibiting the enzyme that breaks down the neurotransmitters. This increases the concentration of neurotransmitters. The problem with MAOI's is that they inhibit MAO in parts of the body other than the brain. This causes problems in the bowels where the enzyme detoxifies chemicals contained in ordinary foods such as yellow cheese and red wine.

St. John's wort is commonly thought to work in a similar manner as MAO inhibitors do. However, researchers in Frankfurt Germany found that St. John's wort did not work as a MAOI to any significant degree. More exciting was a study conducted by Dr. Walter E. Muller and colleagues which found that an extract of St. John's wort is capable of inhibiting serotonin, norepinephrine and dopamine without causing a significant change in other neurotransmitters. If these findings are correct, St. John's wort works like both SSRIs and Wellbutrin but without the side effects that MAOIs have. In fact, many scientists now believe that this balance profile of neurotransmitter re-uptake inhibition may explain why people appear to suffer less sexual side effects with St. John's wort than with other antidepressants.

The effects of St. John's wort, as with all antidepressants, can take up to six weeks to become apparent. No one knows exactly why it takes antidepressants weeks to work since the effects on the re-uptake of neurotransmitters are immediate. Current thinking holds that this may just be the first in a cascade of biochemical steps necessary for reversing the symptoms of depression.

Although the hypericin content of St. John's wort has been the center of much attention, it should be said that scientists are still not sure which ingredient is in fact "the antidepressant". It is quite possible that the various compounds must work together in order to produce the beneficial effects of this herb. More study is needed before we can determine which components of St. John's wort are necessary and which are not.