First-generation antidepressant

First-generation antidepressants includes the two drug classes used widely to treat depression, the tricyclic antidepressants and the monoamine oxidase inhibitors (MAOI), and heterogeneity of chemical form and pharmacological action. While the MAOIs are relatively little used due to their dangerous food and drug interactions, tricyclics remain in use for depression, and also have a number of other applications such as the management of chronic pain.

Both first- and second-generation antidepressants raise the synaptic concentration of monoamine neurotransmitters, most commonly serotonin, less frequently norepinephrine, and occasionally dopamine. First-generation drugs operate on the post-synaptic neuron, inhibiting enzymes that eliminate of the neurotransmitters and thus increasing the concentration in the synapse. MAOIs inhibit monoamine oxidase while tricyclics inhibit catechol-O-methyl transferase.

First-generation drugs are generally less expensive than second-generation. Their side effects tend to be more frequent than the side effects of the second generation, although a first-generation agent may be a reasonable alternative if the different side effects of second-generation drugs make them impractical. Again, the tricyclics are by far the more frequently prescribed group, because the most dreaded side effect of MAOIs, potentially lethal rises in blood pressure, can easily be caused by MAOI interaction with a wide range of drugs and foods.