Antidepressants are drugs that were created to reduce symptoms of depression by targeting various neurotransmitters in the brain. Although initial researchers hypothesize that those with depression have a “chemical imbalance,” this isn’t a proven fact. With that said, increasing levels of certain neurotransmitters such as: serotonin, norepinephrine, and to a lesser extent dopamine seems to improve a depressed individual’s mood to a significant extent.
Most modern day antidepressants fit within one of a few classes such as: SSRIs, SNRIs, or atypical antidepressants. The newer antidepressants are often touted as having less side effects and being better tolerated than older ones. Older antidepressants in the TCA and MAOI classes tend to be associated with more side effects and in some cases dangerous dietary interactions (MAOIs), however they may actually work better for certain subtypes of depression than newer medications.
Types of Antidepressants
Listed below are types of antidepressants starting with more recently developed classes of drugs and ending with the oldest classes of drugs. Most antidepressants on the market fall under one of the following classes:
- SNRI (Serotonin Norepinephrine Reuptake Inhibitors) – Prevent the reuptake of both serotonin and norepinephrine in the brain.
- SSRI (Selective Serotonin Reuptake Inhibitors) – Focus on preventing the reuptake of serotonin in the brain.
- Atypical Antidepressants – Affect the brain differently than other antidepressants on the market. Some affect neurotransmitters other than serotonin and norepinephrine such as dopamine.
- Tricyclic Antidepressants (TCAs) – Affect serotonin and norepinephrine differently than SSRIs and SNRIs.
- Tetracyclic Antidepressants (TeCAs) – Work similarly to TCA’s and have similar structure.
- MAOI (Monoamine Oxidase Inhibitors) – The oldest class of antidepressants that works to increase levels of serotonin, norepinephrine, and dopamine in the brain.
If you read the descriptions, you will understand that each class may have certain advantages and disadvantages upon comparison to other classes. Understand that all classes are considered equal in efficacy, some have more favorable side effects and are better tolerated than others. It should also be noted that there are new antidepressant classes such as SNDRIs (Triple Reuptake Inhibitors) and new atypical drugs (e.g. ALKS 5461) currently in development.
SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)
The SNRI class of drugs work by inhibiting the reuptake of serotonin and norepinephrine. Although all of the drugs within this class affect both serotonin and norepinephrine, some increase one or the other to a more significant extent. Nearly all of the other drugs affect serotonin to a more significant extent than norepinephrine. The only SNRI that tends to affect both serotonin and norepinephrine equally is Fetzima.
So why was the SNRI class developed? There is some evidence that low norepinephrine causes depression in some individuals. Additionally norepinephrine reuptake inhibition seems to give people increases in energy and also is thought to help prevent significant weight gain and sexual dysfunction associated with serotonin reuptake inhibition.
Examples of SNRIs:
- Cymbalta (2004)
- Effexor (1993)
- Fetzima (2013)
- Pristiq (2008)
SSRIs (Selective Serotonin Reuptake Inhibitors)
The SSRI class of drugs works by inhibiting the reuptake of serotonin, hence being called selective serotonin reuptake inhibitors. The earliest SSRIs emerged in the late 1980s and throughout the 1990s. Most people have heard of the drug Prozac, an antidepressant developed by the company Eli Lilly. A majority of doctors and psychiatrists consider SSRIs as first-line treatment options for depression.
Only when a person fails to respond to an SSRI will a patient be prescribed an SNRI or another newer atypical antidepressant. Although this class is very effective and well tolerated, many SSRIs are associated with weight gain and sexual dysfunction. There is also some evidence suggesting that SSRIs could lower testosterone. If you have never been on an antidepressant before, chances are good that your doctor will first see how you respond to an SSRI medication.
Examples of SSRIs:
- Celexa (1998)
- Lexapro (2002)
- Luvox (1994)
- Paxil (1992)
- Prozac (1987)
- Zoloft (1991)
A third class of medications for depression consists of atypical antidepressants. This class has a variety of drugs with unique properties resulting in different neurotransmitter effects than other classes. In other words, the way that atypical antidepressants function is different from drugs in other classes, therefore they cannot be grouped into a specific classification.
Some atypical antidepressants like Viibryd are considered newer, while others like Wellbutrin and Remeron have been around for awhile. The most prescribed atypical antidepressants are Wellbutrin and Viibryd. Viibryd has been prescribed a lot in the past year because it’s considered very new and tends to carry fewer side effects than SSRIs. These are drugs with unique properties that a psychiatrist may prescribe if a person has no success with other classes.
Examples of atypical antidepressants:
- Brintellix (2013)
- Remeron (1996)
- Serzone (1994)
- Trazodone (1981)
- Viibryd (2011)
- Wellbutrin (1989)
TCAs (Tricyclic Antidepressants)
Tricyclic antidepressants are an older class of medications that were developed in the late 1950s. This class of drugs was named for its three ring atomic structure. Most of these drugs are very effective for treating depression, but tend to carry unwanted side effects to a greater extent than SSRIs and SNRIs. Therefore, they are usually recommended as a second or third-line treatment option for depression.
In addition to treating depression, many of these drugs have strong antihistamine properties and help with insomnia. They are also utilized for conditions like fibromyalgia, anxiety, and in some cases to help manage chronic pain. These were the most commonly prescribed antidepressants until the development of SSRIs, and are still regarded as being more effective than other classes when used for depression with melancholic symptoms. Common side effects of this class include: dry mouth, blurred vision, drowsiness, and weight gain.
Examples of TCAs:
- Amitriptyline (1961)
- Anafranil (1998)
- Desipramine (1964)
- Doxepin (1970s)
- Nortriptyline (1964)
TeCAs (Tetracyclic Antidepressants)
It should be noted that there was a class of drugs called tetracyclic antidepressants which were similar in structure to tricyclics, except they contained one more atomic ring in their chemical structure. Many of these drugs work on the H1 histamine receptors, leading to sedating effects. The only TeCA that is commonly used for depression these days is Remeron (also classified as an atypical antidepressant).
Most of the tetracyclic antidepressants were either withdrawn from the market or never ended up being marketed. Additionally most TeCAs tend to work better for conditions other than depression such as schizophrenia.
Examples of TeCAs:
- Amoxapine (1992)
- Loxapine (2012)
- Mianserin (1996)
- Remeron (1996)
MAOIs (Monoamine Oxidase Inhibitors)
The MAOI class of antidepressants are considered “first-generation” treatments due to the fact that they are the oldest. They became heavily utilized throughout the 1950s and treated depression by increasing the amounts of serotonin, norepinephrine, and dopamine in the brain. The class was accidentally discovered when a treatment intended for tuberculosis ended up significantly improving the mood of patients.
The drug ended up inhibiting a slight degree of monoamine oxidase, and researchers discovered that this was the mechanism by which it was producing an antidepressant effect. The MAOI class was commonly utilized from the late 1950s to the early 1970s as a first-line treatment option for depression. The MAOI class is now considered a last-line treatment option for depression mostly due to potentially severe side effects and dietary interactions.
MAOIs interact with foods that contain tyramine and can lead to hypertensive crises if a person is not careful of their diet. Although old MAOIs were classified as hydrazines with irreversible and non-selective inhibition, newer MAOIs carry selective and reversible properties – making them safer and more tolerable. Various side effects from these drugs tend to involve: dry mouth, headache, nausea, and weight gain.
Examples of MAOIs:
- Marplan (1968)
- Moclobemide (1992)
- Parnate (1961)
- Selegiline (2006)
What is the best class of antidepressants?
Most doctors and psychiatrists these days stick with prescribing newer medications to their patients. The newer medications typically fall within the SSRI / SSRI class or the atypical antidepressants. Newer medications tend to be associated with better tolerability, less side effects, and equal efficacy as other drugs on the market.
Only individuals who fail to respond to an array of newer antidepressants will likely end up trying other classes of drugs. All approved antidepressants are regarded as being very effective at treating symptoms of depression, that’s why they’re prescribed. If they weren’t proven drugs and had too many unwanted side effects, they would’ve been removed from the market. The fact is that many individuals respond extremely well to these drugs.
In cases of treatment-resistant depression, other classes of drugs such as TCAs and MAOIs will be pursued. Some people end up responding extremely well to the tricyclic class of drugs, while others find that the oldest class of monoamine oxidase inhibitors (MAOI) works wonders. Those who fail to respond to all types of treatment may end up having to try various antidepressant augmentation strategies, which involve prescriptions of a drug combination to reduce depression.