Antidepressants increase the levels of monoamine neurotransmitters, including serotonin,
norepinephrine, and dopamine, in the brain. The medications were developed based on the theory
that depression results from imbalances or insufficiencies of these chemicals.
The 3 monoamine neurotransmitters share a common metabolism pathway. They are produced
in their respective presynaptic neurons and released to activate their respective receptors
on postsynaptic neurons. Their action is then terminated via their removal from the synaptic
space. This is accomplished by special protein transporters which take these neurotransmitters
back to presynaptic neurons. A portion of the neurotransmitters is recycled, while the remaining
is degraded by the enzyme monoamine oxidase (MAO). Most antidepressants act to inhibit the reuptake
of monoamines, or inhibit their degradation by MAO.
There are 5 classes of antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs);
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs); Tricyclic Antidepressants (TCAs);
Monoamine Oxidase Inhibitors (MAOIs); and Atypical Antidepressants.
SSRIs inhibit the reuptake of serotonin by serotonin transporter,
thereby increasing serotonin level in the synapse.
This class is considered first-line treatment for depression because they act on serotonin
alone and no other neurotransmitters, and therefore have less side effects.
SNRIs inhibit the reuptake of both serotonin and norepinephrine.
Different drugs in this class exhibit different levels of selectivity among the 2 chemicals.
TCAs act similarly to SNRIs, inhibiting both serotonin and norepinephrine reuptake.
However, they also act on some histamine and muscarinic receptors, causing sedation
and anticholinergic effects. TCAs are also used for migraine prevention and nerve pain relief.
These drugs are contraindicated in patients with cardiovascular diseases.
MAOIs inhibit the monoamine oxidase enzymes, MAO-A and MAO-B, responsible for degradation of
serotonin, norepinephrine, and dopamine. Because these enzymes are also present in the digestive
system where they break down monoamines in food, use of MAO inhibitors as treatment for depression
is usually avoided because of the adverse effects due to common drug-food interactions.
Patients taking MAOIs must avoid, for example,
tyramine-rich foods such as cheese, pickles, and cured meat;
as accumulation of this monoamine can cause a rapid and dangerous rise in blood pressure.
Atypical antidepressants include all drugs that act by other mechanisms.
Antidepressants typically take a couple of weeks to achieve the desired effect.
Patients must be closely monitored, especially during these first weeks, for worsening of
symptoms, which may lead to suicidal behaviors. Different antidepressants have different side
effects. The most common include drowsiness, dizziness, nausea, headache, anxiety, insomnia,
weight gain, dry mouth, blurred vision, rash, tremor and sexual dysfunction.
Combination or overdose of antidepressants may lead to a potentially lethal serotonin toxicity,
or serotonin syndrome, with severe neuromuscular and autonomic symptoms.