When a new antidepressant drug is released, everyone wants to be the first to try it. In most cases, people seem to always believe that newer will equal better in terms of depression relief. In most cases, when new drugs get approval to treat depression, they are backed by some heavy marketing, which further brainwashes the public to believe that a certain drug is groundbreaking.
In reality, most of the newer drugs are modified versions of SSRIs and SNRIs. There aren’t drugs being released that have truly unique mechanisms of action that are different from reuptake inhibitors. The only drug being developed that appears completely unique in regards to pharmacological properties is that of ALKS 5461. Another option would be LFMS or low field magnetic stimulation for depression, another treatment that has promise and is drug-free.
Unfortunately most antidepressants on the market are imperfect and will always leave people waiting for the next new thing or next “fix” in regards to an antidepressant. In some cases, a select few people actually do find that they only get relief from the newer drugs than the older MAOIs, tricyclics, SSRIs, SNRIs, and atypicals. There are a couple of new antidepressants that just hit the market in recent years that the mainstream will soon be talking about.
Newest Antidepressants 2014: Fetzima & Brintellix
Although there weren’t any major antidepressants approved in 2014, there were a couple of new releases in 2013. One of these new drugs was considered an SNRI with different inhibition properties compared to all other SNRIs on the market. The other is considered an atypical antidepressant with properties unique from other drugs.
This is essentially an improved version of Milnacipran, an SNRI that has been around since 1996 to treat fibromyalgia and major depression in countries outside of the United States. Although Milnacipran never passed clinical trials in the U.S., Levomilnacipran which contains the “levo” stereoisomer of Milnacipran passed clinical trials in July 2013.
It acts very similarly to Milnacipran, but is unique from other SNRIs in that it inhibits reuptake of norepinephrine to a greater extent than serotonin. Some believe that a more balanced inhibition between serotonin and norepinephrine may improve efficacy, but this speculation is unverified. The side effects associated with Fetzima are similar to current medications on the market.
Be prepared for the same common antidepressant side effects including: nausea, dizziness, insomnia, blood pressure changes, etc. Although this is technically a “new” drug, others would consider it a revised version of an older drug. Some could argue that it was developed because Milnacipran had not gotten approval, and developers knew that with a few tweaks they could get something similar approved.
In trials this drug was referred to as “Lu AA21004” but it has since gotten approval to treat major depression as of September 2013. Just a couple months after the approval of Fetzima, we have an atypical antidepressant hitting the market called “Brintellix.” As of now it is only approved for major depression, but some speculate that it may eventually get approved for various anxiety disorders in the future.
It functions as a SMS (serotonin modulator and stimulator) with a majority of activity geared towards serotonin and 5-HT receptors. It is also thought to affect adrenergic receptors to less of a degree as well as concentrations of acetylcholine and histamine. Like all antidepressants, it had to demonstrate that it was clinically superior to a placebo in large-scale double-blind clinical trials.
In four trials, Brintellix was found clinically effective for depression in two out of four based on the Hamilton Depression Rating Scale (HAM-D). However, in the third trial it was found no more effective than a placebo and in the fourth, there was a high placebo response, but according to other scales such as the MADRS, it was still superior.
It is thought to be a good drug for individuals that have comorbid anxiety along with their depression. The side effects associated with this drug are typical: nausea, diarrhea, dizziness, and sexual dysfunction. This is a unique drug that carries unique properties, but it has similarities with many medications.
Other relatively new antidepressants
Below are a variety of other new antidepressants listed in order based on recency of release. Viibryd is considered the third newest antidepressant to Fetzima and Brintellix. Other drugs that have been released in recent years include: Oleptro, Pristiq, and Emsam. Although these are “new,” they are not necessarily that unique. Oleptro is simply an extended release format of the drug Trazodone, while Pristiq contains the active metabolite of Effexor and Emsam is the drug Selegiline in the form of a “skin” patch.
Viibryd (Vilazodone): This is considered a unique antidepressant that many will want to try because it is not associated with significant weight gain or sexual dysfunction. It was approved in 2011 for the treatment of major depression and functions similar to an SSRI in that it inhibits reuptake of serotonin, but it also affects the 5-HT1A receptor as a partial agonist. Other than Brintellix, this is the second newest “unique” antidepressant that wasn’t modeled after an older medication. The most commonly reported side effect seems to be diarrhea, which can be offset with over-the-counter Imodium.
Oleptro (Trazodone): The antidepressant Trazodone has been around for a long time (since 1981), but it was recently formulated into an extended release pill in 2010. The extended release version is referred to as “Oleptro” and may be preferred by some individuals compared to previous formats of the drug. This is considered an atypical antidepressant that acts mostly as an antagonist on 5-HT receptors, and a partial agonist at the 5-HT1A receptor. Unfortunately this is merely a repackaging of an older drug, so not really an improvement.
Pristiq (Desvenlafaxine): A good analogy to describe this drug: Pristiq is to Effexor as Lexapro is to Celexa. In other words, it is supposed to be an improved version of Effexor and contains the synthetic active metabolite that results in an antidepressant effect. The company that makes Pristiq (Wyeth) is trying to get everyone who is on Effexor to convert to Pristiq to boost overall sales. Their patent had expired for Effexor, so this new “modified” formula is a good way to get back premium business that they had with Effexor. Despite chemical similarities, people that have tried both drugs still note differences between the two drugs. Although this is a newer antidepressant, it’s really just a repackaged version of Effexor.
Emsam Patch (Selegiline): It was known since 1967 that Selegiline was effective for depression. However, it wasn’t until 2006 that it was approved and manufactured in the form of a transdermal (skin) patch. As an antidepressant Emsam works as an MAOI which can be utilized for both major depression as well as Parkinson’s disease. There are some advantages to delivering the drug as a skin patch including: bypassing the small intestine, bypassing the liver, and preventing a hypertensive crisis (associated with MAOIs). Unlike other MAOIs, Emsam doesn’t requires dietary modifications and some believe that as a patch, the drug is more likely to maintain steady levels in the blood stream. Although this antidepressant is essentially an old drug that has been rebranded, it’s transdermal delivery makes it more appealing to some.
Cymbalta (Duloxetine): This SNRI was approved in 2004 to treat major depression and neuropathic pain. It has since received approval to treat a variety of other conditions such as generalized anxiety and fibromyalgia. The ability of this drug to provide clinically effective pain relief is what distinguishes it from other antidepressants on the market and contributes to its heightened popularity. Although it’s been 10 years since this medication hit the market, it has become the top selling and most popular antidepressant of the past year (it is inevitably the most prescribed as well).
Newest antidepressants in development
There are many new antidepressants being researched for potential therapeutic usage in the future. The FDA has rigorous standards for all medications, which is why the approval process can take years after a drug has been developed. There’s a lot more that goes into getting a new drug on the market than most people care to understand. Below are a few new drugs that may hit the market in upcoming years. (For the latest developments – read the article: “New Antidepressants 2018“).
- ALKS 5461: This is a new drug that is showing considerable promise and is something different than your run-of-the-mill serotonin-acting drug. ALKS 5461 is essentially a combination drug that includes Suboxone, but theoretically should be non-addictive because it also contains Samidorphan. It is well documented that using Suboxone for depression can be life-changing for certain individuals. As of now this drug has received fast-track status due to how well people are responding with minimal side effects. Assuming all goes according to plan with this drug, it could hit the market in 2016.
- SNDRIs (Triple Reuptake Inhibitors): There is a new class of drugs in the pipeline called “Triple Reuptake Inhibitors” a.k.a. SNDRIs (Serotonin Norepinephrine Dopamine Reuptake Inhibitors). In other words, they are attempting to address the fact that low norepinephrine can cause depression and address both serotonin and dopamine. Additionally it is debated as to whether serotonin vs. dopamine is more of a contributing factor to low mood. Many experts believe that targeting all three of these prominent neurotransmitters could fix the problem. The only downfall associated with these drugs is that they aren’t really anything creative, they are simply throwing another neurotransmitter in the mix in hopes that the public becomes brainwashed by the new mechanisms. In reality, a person can already utilize antidepressant augmentation strategies such as Adderall or Wellbutrin and stimulate all three neurotransmitters.
- Ketamine: Slowly but surely professionals are starting to consider illicit substances for cases of treatment-resistant depression. One such substance that has been showing considerable promise in recent years is ketamine. Many people who are trying ketamine in a controlled setting are finding that it not only alleviates their depression, but it does so very quickly. Some believe that ketamine helps enhance activity of neurotransmission and receptors, thus repairing damages and blockages caused by depression. Recently a ketamine nasal spray for depression was developed and found to be very effective.
- Psilocybin (Magic Mushrooms): It has been discovered that using psilocybin for depression can be very helpful for a majority of people. Although magic mushrooms are considered an illicit substance, many have found them helpful for boosting both mood and spirituality. Many have gone on a “trip” and claimed that their entire outlook on life changed for the better, and that this change was relatively “long lasting.” Some researchers are attempting to create a similar substance to psilocybin in pill form that retains the antidepressant properties without the potentially psychedelic side effects.
Should you be excited about new antidepressants?
In most cases, the answer is a resounding “no.” Most people get caught up in the hype of a new drug, and that’s exactly what the drug companies want. The drug companies create fancy graphics, advertisements, and tout the drug as being the next best thing to hit the market. In most cases, these new medications are no more effective or tolerable than older drugs.
Although most medications shouldn’t be too exciting, there are some promising therapies in the works for the future. Anything that works differently than an SSRI, SNRI, etc. will get my attention. One such drug that I already mentioned is that of ALKS 5461 – it is showing significant efficacy in initial trials. Even that drug though may not end up getting approved, so it’s nothing to get excited about until it is: A) Approved and B) Generates a positive response.
The future of all medicine lies in finding certain genetic abnormalities that could contribute to major depression, and then targeting them with genetic therapy. We are a significant ways away from utilizing genetic therapy to treat mental illness, but I’d say this would have the potential to actually cure someone of their disease rather than keep people trapped on the pharmaceutical hamster wheel of antidepressant medications.