Neurotransmitters and the side effects of antidepressants

We  certainly wish that antidepressants in particular, and all psychiatric medications in particular were free of side-effects. It would be a boon to our patients, and their families. Sadly, there is no such thing as a medication without any risk of side-effects. Even over-the-counter medications such as Tylenol, Benadryl an aspirin can have pretty serious side-effects.

Some side-effects of medications are related to dose — the higher the dose, the greater the risk of side-effects.

Antidepressants (and all other psychiatric medications) have 2 additional, common reasons behind their risk of negative effects:

  • the neurotransmitters they target are not selective, i.e. they don’t just regulate mental well-being.
  • the medications themselves are not selective, i.e. they don’t act only on the neurotransmitters related to their main action.

Neurotransmitters are chemicals that our nervous system makes and uses to communicate between its various parts. When we feel any physical sensation – pain, heat, cold, taste, smell – our body uses neurotransmitters to communicate the sensation to the brain. Our brain uses neurotransmitters to communicate to our muscles to move in response to the sensation, to move away from potentially harmful sensations and closer to pleasurable ones. A few examples of neurotransmitters include chemicals such as serotonin, dopamine, norepinephrine, acetylcholine. There are several others.

When we say, “neurotransmitters are not selective,” it means that a particular neurotransmitter does not just have one particular action. As an example, the neurotransmitter serotonin that is believed to help regulate mood and which many antidepressants target, in addition to mood, also regulates appetite, pain, proper function of our stomach and intestines, sexual function. So, any antidepressant that improves mood by regulating the actions of serotonin, will also end up regulating those other functions – some in desirable directions, others in undesirable ones.

When we say, “antidepressants are not selective,” we mean that antidepressants don’t work on just one neurotransmitter. For example, medications belonging to the same group as Prozac were initially called selective serotonin reuptake inhibitors (SSRIs). But now it’s well known that they affect, other neurotransmitters besides serotonin. They have potent effects on fewer neurotransmitter systems than the older antidepressants, but they are not really selective.So, the roots of their side-effects lie not just in the fact that serotonin regulates other functions besides mood, but also in the fact that they affect other brain chemicals that also have multiple functions.

For example, a medication that works on serotonin, may also affect another neurotransmitter called norepinephrine, which is also an important regulator of the function of our heart, lungs, gut, bladder, eyes, arteries and veins. In this case, the potential side-effects include not just those related to Serotonin regulation, but also those related side-effects like palpitations, urinary problems, vision problems and blood pressure changes.

In essence, antidepressants work on multiple neurotransmitters, each of which has multiple functions, most of which are not directly related to mood regulation. This is what explains most antidepressant side-effects.

Dheeraj Raina is a psychiatrist who practices at the Depression Clinic of Chicago.

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