Antidepressants: The Tricyclics 

Antidepressant Medication : Tricyclic Overview 

The tricyclic antidepressants were accidentally discovered in the 1950s. Researchers studying the use of a new drug, imipramine for schizophrenia, found that rather than being effective for schizophrenia, it actually had the effect of relieving depression in many people. The new drug later named Tofranil, and the related compounds, became known as tricyclic antidepressants because of the shape of their molecular structure. 

After several hundred studies, it has been found that depressed patients taking tricyclic antidepressants have improved much more than similar patients taking placebos.  However, it must be noted that the antidepressants usually must be taken for at least 10 days before such improvements may begin.  Approximately 60% to 65% of patients taking tricyclic antidepressants seem to be helped by them.

 The relapse rate after discontinuing the use of tricyclic antidepressants is quite large.  Many studies have found that when depressed people stop taking tricyclics immediately upon relief of symptoms, they run a risk of as much as 50% of relapsing within a year.  However, if they continue taking these drugs at full dosage for five months or so after being free of the depressive symptoms, a practice called "continuation therapy", the risks for relapse are reduced significantly. Researchers also found that when these antidepressants are taken at full dosage for three or more years after the initial improvement of symptoms, a practice called "maintenance therapy", the risk of relapse is reduced even more.  As a result of this research, many clinicians are known to keep patients on these antidepressants indefinitely. 

Researchers have concluded that tricyclic antidepressants reduce depression by acting on neurotransmitter "reuptake" mechanisms.  Messages are carried from one neuron across a synaptic space to a receiving neuron by a neurotransmitter, a chemical released from the nerve ending of the sending neuron.  There is however, a complication to this process.  While the nerve ending is releasing neurotransmitter, a pump-like mechanism in the  sending neuron is also trying to recapture the extra neurotransmitter that has been released. The purpose of this process is to prevent the neurotransmitter from remaining in it space between the two neurons for too long a period of time, and repeatedly stimulating the receiving neuron.  It is believed that this pump-like reuptake mechanism is actually too successful in some people, reducing norepinephrine or serotonin activity too much.  The reduced activity of these neurotransmitters may result in clinical depression.  Apparently tricyclic antidepressants block this reuptake process, thus increasing the level of neurotransmitter activity. 

If tricyclic antidepressants act immediately to increase norepinephrine and serotonin activity and that efficiency, why do the symptoms of depression continue for 10 or more days after drug therapy begins?  There is now growing evidence that when tricyclic antidepressants are ingested, they initially slow down the activity in the neurons that use norepinephrine and serotonin.  The reuptake mechanisms of these cells are immediately corrected, thus allowing more efficient transmission of the neurotransmitters, but then responding to the change by releasing smaller amounts of these nuerotransmitters.  After a week or two, the neurons finally adapt to the tricyclic antidepressants and go back to releasing normal amounts of the neurotransmitters.  Now the corrections in the reuptake mechanisms begin to have the desired effect in that the neurotransmitters reach the receptor neurons in greater numbers, hence triggering an increase in the level of firing from the sending neuron and producing a decrease in depression. 

Tricyclic antidepressants are prescribed much more often than the MAO inhibitors.  They are much less dangerous than the MAOI's, and do not require restrictions of a persons diet.  Also persons taking tricyclic antidepressants typically show higher rates of improvement than those taking MAO inhibitors.  However, there are some individuals that respond better to the MAO inhibitors than either tricyclic antidepressants or the newer drugs described as second-generation antidepressants or selective serotonin reuptake inhibitors (SSRI’s) which seem to be the most popular. 

Information from Ronald J. Comer’s Abnormal Psychology 

Additional Information and webpage by Paul Susic  MA Licensed Psychologist   Ph.D. Candidate  (Health and Geriatric Psychologist)

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