How Antidepressants Work


How Antidepressants Work: Each Type Works Differently

Answering the question, “How antidepressants work?” may yield different answers, as there are many types of antidepressants available in the market as of today. Antidepressants may cause different effects on the brain’s neurological activity and thus, they are categorized accordingly.

Generally, how antidepressants work can be summarized into this explanation: Antidepressants have the capacity to block certain neurotransmitters such as serotonin, norepinephrine, and dopamine (neurotransmitters responsible for the control of mood and emotions) on the synaptic cleft before they are absorbed again in the system. Therefore, if these neurotransmitters are not absorbed and broken down in the system, they remain to be present in high levels on the brain, and since these are “happy chemicals,” the effect of increased serotonin, norepinephrine and dopamine on the brain, specifically the limbic system, is a dramatic rise on one’s mood.

In line with this, antidepressants are classified according to what type of neurotransmitter do they block. One class of antidepressant blocks only serotonin neurotransmitters, on the other hand, another type may block both serotonin and norepinephrine. This is primarily how antidepressants work as according to their class.

There are four, identified and accepted classifications of antidepressants: 1) SSRI or Selective Serotonin Reuptake Inhibitors, 2) TCA or Tricyclic Antidepressants, 3) MAOI or Monoamine Oxidase Inhibitors, 4) NaSSA or Noradrenergic and Specific Serotonin Antidepressants.

As additional information on how antidepressants work, the following is a brief description about each of the class’ mechanism of action:

Selective Serotonin Reuptake Inhibitors (SSRI)

SSRIs are the type of antidepressants that target the neurotransmitter, serotonin. It prevents the absorption of the said chemical on the presynaptic cleft of the neurons, thereby increasing its levels on the brain. Serotonin is sometimes referred to as the “happiness hormone” (although it’s quite really not a hormone) and an increase in its level prevents symptoms of depression. Popular drugs under this category are fluoxetine (Prozac) and sertraline (Zoloft).

Tricyclic Antidepressants (TCA)

Like SSRIs, TCA also blocks certain neurotransmitters, which in this case are norepinephrines. Popular drugs under this category are imipramine (Tofranil), amitryptiline (Elavil) and clomipramine (Anafranil). However, TCA has serious side effects because norepinephrine has a role to play in the autonomic central nervous system of the body. These side effects involve: tachycardia (rapid heart rate) and hypotension (low blood pressure). Physicians are expected to be careful in prescribing and administering this type of drug, as its toxic effects are lethal.

Monoamine Oxidase Inhibitors (MAOI)

MAOIs do not actually block neurotransmitters; instead, it blocks the chemical enzymes that break down neurotransmitters (serotonin and norepinephrine) in the synaptic cleft. In a sense, it creates the same effects as that of SSRIs and TCAs in increasing the level of happy neurotransmitters on the brain. The mechanism of action of MAOIs proves how antidepressants work in increasing the mood of a person not by blocking the neurotransmitter’s reuptake but by blocking the enzyme that breaks down the said neurotransmitters.

Popular MAOIs include selegiline (Eldepryl) and phenelzine (Nardil). However, when taking MAOIs, one should not take foods that contain tyramine as this can cause a hypertensive crisis. Tyramine-rich foods consist of cheese (except for cream and cottage), sausages, cured meat and preserved goods.

Noradrenergic and Specific Serotonin Antidepressants

NaSSA works differently from all the other antidepressants, but it also yields the same effect of increasing the level of serotonin and norepinephrine. NaSSA’s block the negative feedback mechanism of the body, which then increases the concentration of these neurotransmitters. Feedback mechanism refers to the involuntary and automatic system of the body to lower down chemical substances that are in high levels.

Popular drugs under this category are: Trazodone (Desyrel) and Mirtrazipine (Remeron). The common side effects of this drug class are dry mouth, drowsiness, increase in appetite and weight gain.

It is important to note that how antidepressants work depends greatly on its composition and target neurotransmitters. That is why, it is highly important first to consult the psychiatrist before starting on any antidepressant pharmacologic treatment.