Types of Antidepressant Medication: First & Second Generation

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  • 0:01 Antidepressants
  • 0:45 Brain Chemistry
  • 2:04 First Generation
  • 4:33 Second Generation
  • 5:43 Lesson Summary
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Lesson Transcript
Instructor: Rebecca Gillaspy

Dr. Gillaspy has taught health science at University of Phoenix and Ashford University and has a degree from Palmer College of Chiropractic.

First-generation antidepressants like TCAs and MAOIs can be effective, but come with many unwanted side-effects. Second-generation antidepressants like SSRIs and SNRIs have similar benefits, but are thought to have less severe side effects.


We all have those occasional moments when we feel sluggish, down in the dumps and bored with life. These are never fun feelings to have, but most of us bounce back and return to our normal state of happiness on our own. For some people, however, this low feeling does not lift, and they fall into a state of depression, which is defined as a mood disorder that leads to feelings of sadness and a loss of interest in life. These individuals may need a bit of help to fight against depression. This help may be provided by one of the types of antidepressant medications. In this lesson, we will describe first- and second-generation antidepressants and learn how they affect the chemicals in a depressed person's brain.

Brain Chemistry

What causes depression is not fully understood, but it's generally thought to have to do with brain chemistry. Inside your brain, there are collections of nerve cells called neurons. These neurons communicate with each other by exchanging neurotransmitters, which are tiny chemical messengers. For example, if one neuron wants to send a message to a second or target neuron, it will dump the appropriate neurotransmitter into a gap between the neurons. These chemical messengers get picked up by receptors on the target neuron. If there are any leftover neurotransmitters remaining in the gap after the message has been transmitted, those chemicals are reabsorbed back into the first neuron.

Some neurotransmitters, such as serotonin, norepinephrine, and dopamine, carry a message that influences your mood, emotions and general feeling of wellbeing. These neurotransmitters are naturally made in the brain but may be available in lower than normal quantities in the brain of a person with depression. Antidepressant medications work by increasing the concentration of certain neurotransmitters within the brain. The different types of antidepressants affect the concentration levels of different neurotransmitters.

First Generation

First-generation antidepressants were the first effective antidepressants to be developed, yet their ability to counteract depression was discovered by accident. In the 1950s, medications were being tested for the treatment of tuberculosis, which is an infection that affects the lungs. Surprisingly, these drugs were found to have a mood improving side effect.

This lead to the discovery of the first generation of antidepressants, which consist of two classes of drugs: tricyclic antidepressants, or TCAs, and monoamine oxidase inhibitors, which are also referred to by their abbreviation MAOIs. TCAs and MAOIs are able to affect depression because they increase brain levels of serotonin and norepinephrine; however, they accomplish this task in different ways.

TCAs block the reabsorption or reuptake of the neurotransmitters back into the first communicating neuron. As we learned earlier, when one neuron wants to talk to another, it dumps its neurotransmitters into a gap between it and the target neuron. Any leftover neurotransmitter remaining in the gap after the message is sent typically gets reabsorbed into the first cell. But when TCAs are in the picture, the reabsorption cannot occur, which makes more of the chemicals available in the space. This increased concentration helps push the neurotransmitters toward the target cell and strengthen the feel good message.

MAOIs do not prevent reuptake of the chemical messengers. Instead, they prevent the breakdown of the neurotransmitters by inhibiting the action of monoamine oxidase. Under normal circumstances, monoamine oxidase is an enzyme that removes neurotransmitters from the brain. When MAOIs are in the picture, this action is prevented, and concentrations of the chemicals are allowed to increase. This increase is thought to boost the mood-lifting effect of the chemical message.

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