Antidepressants are some of the most commonly prescribed drugs in the world. However, they are not all alike, and in many cases, an antidepressant that works well for one person does not work at all for another. Dr. Alexander Neumeister, who has studied neuroscience and psychiatry for over 25 years, sheds light on the major classes of antidepressants and how they differ concerning side effects, mechanism of action, and more.
Before looking at specific drug classes, it’s important to review the primary function of antidepressants. In the brains of people with depression, there is nearly always an imbalance of certain chemicals known as neurotransmitters. The three neurotransmitters that are most relevant to depression are serotonin, norepinephrine, and dopamine.
In a non-depressed person, serotonin regulates appetite and sleep and provides a sense of well-being, norepinephrine helps with energy levels, and dopamine is associated with feelings of pleasure and reward. When there is an imbalance in any of these three neurotransmitters, however, symptoms of depression can result. The function of antidepressant drugs is to correct the imbalance, thus eliminating the depressive symptoms.
SSRIs, or selective serotonin reuptake inhibitors, are one of the most commonly prescribed types of antidepressants. As the name suggests, they act in the brain to prevent serotonin reuptake. In other words, they force more serotonin to remain available for use. The most well-known SSRI is fluoxetine (Prozac), although there are many others available.
SSRIs are tolerated well by most people, and doctors frequently prescribe them. However, they are not without side effects. Side effects vary from SSRI to SSRI, but commonly include gastrointestinal disturbances (e.g., nausea, changes in bowel habits), sexual problems, weight changes, and sleep changes. People who are bothered by side effects but wish to keep taking an SSRI may want to try citalopram (Celexa), which seems to cause the fewest problems.
SNRIs, or serotonin and norepinephrine reuptake inhibitors, work the same way as SSRIs, but they affect norepinephrine in addition to serotonin. For this reason, they are often more effective, but they also come with a higher risk and a greater range of side effects. Venlafaxine (Effexor), for example, causes unpleasant withdrawal symptoms in many people if even a single dose is missed.
Tricyclic antidepressants (TCAs) are named after the three rings in their chemical structure. Like SNRIs, they increase the availability of serotonin and norepinephrine, but, unlike SNRIs, they also affect other brain chemicals. TCAs include amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor), and others. Some examples of side effects experienced by people taking TCAs are weight gain, problems with low blood pressure, and drowsiness.
Monoamine oxidase inhibitors (MAOIs) work differently than the antidepressant classes above. Instead of inhibiting neurotransmitter reuptake, they inhibit an enzyme called monoamine oxidase. The monoamine oxidase enzyme is responsible for breaking down serotonin, norepinephrine, and dopamine in the brain, so, when it is inhibited, more of those three vital neurotransmitters remain available for use.
MAOIs include isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate). However, MAOIs usually are prescribed only when other options are not available. This is due to the risk of interactions with other drugs and the need to follow a special diet. People taking MAOIs must avoid foods containing a substance called tyramine, so many everyday items, including alcohol, cheese, chocolate, and more, are off-limits. Even outside of diet and drug interaction issues, there is a risk of side effects. The most common side effects are a dry mouth, gastrointestinal issues, headache, drowsiness or insomnia, and dizziness or low blood pressure.
SSRIs, SNRIs, TCAs, and MAOIs, are the most critical antidepressant classes to be familiar with. However, they are not the only options on the market. It’s not necessary to know about every single one, but four more specific drugs don’t fit into the classes above that are worth mentioning. Two of them, lithium and bupropion (Wellbutrin) require a prescription, and the other two, St. John’s Wort and caffeine, are available over the counter.
You may recognize the name lithium from the periodic table of elements. People with bipolar disorder, however, identify it as the drug they take to stay well. Bipolar disorder is like depression, but it also occasionally includes episodes of mania or excessive energy. Standard antidepressants are not recommended to treat the depression that occurs with bipolar disorder because they have the potential to produce manic episodes, which are just as undesirable as depression. Instead, lithium, which is known as a mood stabilizer, is used. It helps prevent both mania and depression. The downside, of course, is the risk of side effects. Blood tests need to be done periodically, and fluid balance alterations may occur.
Bupropion (Wellbutrin) is a member of the NDRI, or norepinephrine and dopamine reuptake inhibitor, class of antidepressant drugs. It increases the availability of norepinephrine and dopamine, resulting in an activating effect that is particularly helpful in cases of atypical depression. Also, bupropion does not seem to cause weight gain or sexual dysfunction, which makes it appealing to users of other antidepressants who are affected by those two very frustrating side effects. However, bupropion does come with an increased risk of seizures, and it is vital to avoid alcohol while taking it.
St. John’s Wort
St. John’s Wort is an herbal remedy that is available without a prescription. It works by affecting serotonin levels, and it is not associated with many side effects. However, as with any herbal supplement, it is essential to check with a doctor or pharmacist before starting to take St. John’s Wort, especially since drug interactions can easily occur. Also, be aware that the FDA does not regulate supplements, so there is no guarantee the dose advertised on the bottle is the dose you are receiving.
Although it is rarely thought of as an antidepressant, caffeine does have some interesting antidepressant properties that make it worthy of inclusion here. More study is required, but the research that has been done so far indicates that it is surprisingly effective. Coffee and energy drinks are easily accessible sources of caffeine, of course, but, for those interested in using caffeine as an antidepressant, a slow-release pill may be better, as it decreases the chance of an unpleasant “crash” hours later.
Light therapy is a particularly effective and mostly well-tolerated treatment for patients who either suffer from depressive episodes during the fall and winter months and show a full remission from their symptoms during spring and summer or show a worsening of their depressive symptoms during the winter period. “In many cases light therapy alone is a sufficient treatment, if administered regularly. Light therapy can also be combined with medication treatment or psychotherapy in those individuals who are not treated sufficiently with light therapy alone,” stated Alexander Neumeister.
In summary, there are many different types of antidepressant options available. Only you and your psychiatrist can determine which is best for you. However, knowing how each type works and knowing what side effects are commonly experienced can be very useful. Use this knowledge when you talk to your doctor. The more you know, the better you will be able to advocate for yourself.
About Dr. Alexander Neumeister:- Dr. Alexander Neumeister is a neuroscientist and psychiatrist focusing on the intersection between pre-clinical research and psychiatric treatment. The author of more than 130 papers in leading neuroscience journals, he has been a respected member of the scientific community for over 25 years. Dr. Neumeister is also a classically trained pianist and continues to be a staunch patron of the arts.
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