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Do Antidepressants Work?

Depression is a very common emotion that everyone experiences at some point in life. In some cases depression is triggered by external events and environmental factors. In other cases, no matter how good someone’s environment or healthy their habits, they feel a depression that they cannot shake. This inevitably leads people to search for a solution to how crappy they feel. Sometimes, people just want a quick fix: pop a pill and feel happier as soon as possible.

Other times, people resort to popping antidepressant pills because no matter what they try, they cannot find relief from their depression. Prior to taking antidepressant pills though, many people wonder whether they are actually worth trying. One of the biggest questions regarding pharmaceutical treatment for their depression is relatively obvious: “Do antidepressants work?” Many will find that the answer to the question is completely subjective.

For some people antidepressants are a godsend that provide relief from depressive symptoms for years. In other cases, they can actually make depression deeper and/or lead to significant unwanted side effects such as weight gain and sexual dysfunction – making a person feel worse about themselves. From a scientific perspective, antidepressants are considered to “work” because they have gone through years of clinical testing and have been approved by the FDA to treat major depression.

Do Antidepressants Work? Based on science, “yes.”

Based on scientific evaluation and thorough studies, antidepressants technically work. They are currently the best option to treat endogenous depression, because it isn’t caused by external or lifestyle factors. The type of major depression that isn’t affected by diet, exercise, socialization, etc. is the type that usually needs drugs to treat. Although the hype that antidepressants treat a chemical imbalance is nothing more than a marketing ploy, they are effective at improving mood.

In most cases, major depression isn’t necessarily caused by a “chemical imbalance,” it’s caused by genetic factors. In order to change these genetics, we would need to identify the genes responsible for causing our depression, and modify them; this is a perfect solution. However, since we lack the science and technology to pull off a cure, we do our best to treat the problem by patching it with medication.

Medication then changes brain chemicals and makes us feel better for awhile. Although they don’t work for everyone, they work for enough people to establish clinical significance in double blind, placebo-controlled studies. For a substance to show significance, it must be evaluated with a reliable test such as the Hamilton Depression Rating Scale (HAM-D). The evaluations must show that the drug significantly improves mood compared to a placebo.

How Antidepressants are Developed and FDA Approved

The process for developing antidepressants is just like any other drug, except trials may take even longer. There have been many ideas for drugs that have been submitted to the FDA and rejected. Additionally there are other drugs that go through clinical trials and have too harsh of side effects to get approval. And finally there are others that show initial promise, but don’t establish significant efficacy in clinical trials.

  1. Lab studies: Before a new drug is even submitted to the FDA as a potential “new drug,” it must show some promise in lab studies. A company must initially have substantial evidence suggesting that their drug is effective and that it will be well-tolerated. Drug companies don’t just pick potential antidepressants at random, they pick drugs with good results in initial lab tests.
  2. Investigational New Drug (IND): Following initial lab studies, an investigational new drug application needs to be submitted to the FDA. This application is a necessary part of the process, it must be approved for human testing to advance to clinical trials. The FDA will review the potential investigational drug to get a better understanding of how it works, potential risks, and whether it could show promise.
  3. Clinical Trials: When the investigational new drug application passes judgment of various representatives, clinical trials can begin. Following submission of an investigational new drug application, a company must wait a full 30 days before beginning clinical trials. This gives the FDA time to gather more information regarding the proposed study. Eventually clinical trials will begin to better understand the efficacy and side effects of the drug. Participants in the clinical trials must be protected and the drug must not cause harm.
  4. New Drug Application (NDA): Once a drug has shown efficacy in clinical trials, a company may decide to submit a new drug application to the FDA. This application is what the FDA must eventually approve before the drug hits the U.S. market. The company behind the drug must already have significant evidence demonstrating efficacy and tolerability of the substance. A team of physicians, chemists, pharmacologists, scientists, and statisticians will review the new drug application and initial proposal.
  5. FDA Approval: Following years of clinical trials and submission of a new drug application, a panel of experts decide whether the drug should be granted approval to treat a specific condition. In the case of antidepressants, they will look at whether the drug is safe, its side effect profile, how it works, and most importantly, whether it legitimately treats depression.
  6. Patent protection: Once a new drug hits the market, you’ll end up paying premium price for it. This is why many companies are seeking to make slight improvements on older antidepressants and rebrand them for increased profits. Patent protection typically lasts around 10 years for an antidepressant. Take Cymbalta for example, the drug was approved in 2004, but its patent expired in 2013, allowing companies to make cheaper generic versions.

Studies Suggesting Antidepressants Don’t Work

There is some evidence suggesting that antidepressants may not work as well as people had initially thought. The fact is that some research suggests that: these drugs can cause increased depression, they do more harm than good over the long-term, and that some people find no relief when trying these drugs. There also has been evidence that companies selectively-publish studies based on whether they work in favor of getting a drug approved during clinical trials.

Cause depression / suicidal thinking: There is also evidence suggesting that antidepressants can cause depression and suicidality. Even though they may improve these symptoms in certain people, for others they can make the problem worse. This further accentuates the fact that these pharmacological treatments are imperfect and at best a guess as to what is wrong inside the brain. Initially it was stated as fact that “serotonin” was the culprit for depression, but now researchers are throwing other neurotransmitters such as norepinephrine and dopamine into the mix. In reality, the depression is caused by genetic factors and these drugs have shown efficacy as temporary patches.

More harm than other treatments: Additionally, some evidence suggests that these drugs may cause more harm than benefit in the long-term. In one 18-month study comparing four treatment options (2 therapies, an antidepressant, and a placebo), individuals treated with an antidepressant were the least well. It could be argued though that this study was conducted in 1992 and utilizing an older tricyclic antidepressant. Could a newer medication have improved results for those treated with the antidepressant? It’s certainly a possibility.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1417430

Worsened long-term outcomes: In a study published in 2003, it was found that treatment with antidepressants may actually worsen long-term outcomes. Although they may initially work, eventually a person will build up a tolerance to their effects. When the antidepressant treatment is stopped, individuals can experience relapse and unbearable withdrawal symptoms. Despite the fact that antidepressants are considered a great therapy for major depression, long-term pharmacological treatment may worsen the illness.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12633120

Selective reporting of studies: Despite the rigorous FDA evaluation process that antidepressants must pass in order to hit the market, some evidence suggests that the drug companies may be cheating the system to get their drugs approved. There is significant evidence suggesting that there is selective reporting of clinical trials. In other words, the drug companies only publish the clinical trials that show significant efficacy, while discarding ones that don’t show promising results.

  • Source: http://www.nejm.org/doi/full/10.1056/NEJMsa065779

Treatment-resistant depression: Many people have treatment-resistant depression. If you asked a person with this type of depression if antidepressants work, they might give you a smug look followed by a cold smack across the face. If antidepressants worked for these individuals, then they wouldn’t have what is referred to as “refractory” or “resistant” depression. These are individuals that have tried multiple approved drugs and found no relief in their symptoms.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17521891

Other problems associated with antidepressants

There are several other problems associated with antidepressant usage. These problems include things like: overuse (doctors prescribing them too often), side effects (can be unbearable), and withdrawal difficulties (promote dependence on the drug).

Overprescribed: The fact is that antidepressants are given out these days like candy. If someone goes into your average general practitioner and says “I’m depressed” or “I’ve been feeling really down lately,” in many cases a doctor will write up a prescription for the latest trendy antidepressant. Many doctors are grossly incompetent when it comes to prescribing antidepressants, simply because they really don’t understand the potency of these drugs. These drugs should only be used in severe cases of major depression and only by a competent psychiatrist. Someone who is feeling depressed over a breakup or overwhelming work stress should not be taking one of these drugs. For mild to moderate depression, some studies suggest that these drugs work no better than a placebo.

Side effects: In many cases the side effects associated with these drugs are unbearable. They may make you feel dizzy, gain weight, or unable to orgasm. There are many unwanted antidepressant side effects that people have to put up with even though they are uncomfortable.  Although you may get relief from depression, you may not be able to orgasm or may pack on 20 lbs. in a year. Additionally in some cases, men come to the conclusion that antidepressants lower testosterone levels.

Withdrawal difficulties: Over time, your brain becomes dependent on the antidepressant for general functioning. You may feel better in the first few months of treatment, but eventually your brain will adapt to the drug and expect more of it for the antidepressant effect. If you withdraw from it, you may go into relapse or experience grueling withdrawal symptoms, many of which are nothing short of hellacious. This leads many individuals to feel as if they will never get better and that they are stuck in the trap of depression for life.

What to understand before taking an antidepressant

There are several points that people need to understand when it comes to these drugs. Many of these are truths that people fail to recognize or fully comprehend.  The truth is that antidepressants won’t work for everyone, they can make depression worse, and they usually do not provide relief from symptoms forever.

  • Antidepressants don’t work for everyone: Despite showing efficacy in clinical trials, drugs sometimes just don’t help certain individuals. There are cases of treatment-resistant depression that aren’t helped by any sort of drug.  If antidepressant drugs don’t work for you, understand that you are not alone.  Some evidence suggests that up to 20% of all people with major depression have a treatment-resistant form.
  • Antidepressants can make depression worse: There is evidence that some people have bad reactions to antidepressants. Even clinical trials of these medications show that they can make some people even more depressed and lead to suicidal thinking. This shows that altering serotonin levels is not always going to improve mood.
  • Antidepressants can work extremely well: For some individuals, antidepressants work extremely well. They may notice immediate improvement in mood and be able to feel normal for once in their life. If these drugs work well for you, that’s great – they are helping many people. It is important to acknowledge that antidepressants are literally a life-saver in some cases.
  • Whether antidepressants work depends on the person: Everyone is different, therefore whether a certain drug works will depend largely on the individual. Various biological, genetic, and environmental factors can contribute to the efficacy of a drug. Some people may not respond to any medication, while others may notice improvement on a specific medication. If your depression is caused by a circumstance that can be changed, it would likely better be resolved with lifestyle changes and therapy.
  • Antidepressants act as a temporary patch: For many people, antidepressants are used as a temporary patch. When life gets tough, they take an antidepressant to help make it through a tough time. The only problem with this is that in certain cases, the “patch” may be covering up a deeper issue that could be resolved without an antidepressant. An example would be someone caught in an abusive relationship. If the person cannot break free from the relationship, they may resort to an antidepressant drug to patch their depressed emotions instead of just leaving the relationship. Additionally people cannot expect these drugs to work forever. Even if they work for a few years, you will eventually build a tolerance and they will stop working.
  • Antidepressants “numb” some people: Instead of making a person feel less depressed and/or happier, in many cases antidepressants simply prevent a person from feeling emotions. They may feel like a complete robot, which may make them more prone to questionable or risky behavior. Inability to feel emotions can be dangerous because it makes people out of touch with reality.
  • Antidepressants can cause a chemical imbalance: Most people usually do not have a chemical imbalance prior to taking antidepressants. What really happens is that a certain drug changes chemicals in the brain to make a person not feel depressed. Taking an antidepressant doesn’t make someone feel “normal,” rather it drugs their brain into feeling less depressed. Although these drugs are not illicit because they are safe and non-addictive, they can actually create a chemical imbalance if used over a long-term. In some cases people become dependent on these drugs because they cannot function without them.
  • Antidepressants are an imperfect solution: As of now, using antidepressants is an imperfect solution to the problem of major depression. When it comes to most types of mental illness, the treatments on the market are far from perfect. Many sometimes don’t work well enough to justify the wicked side effects. Antidepressants won’t work forever, but as of now, they are one of the best treatments available for overwhelming depression.
  • Antidepressants should be a last-resort: It is important to get medically evaluated to rule out other problems that could be causing depression before taking these drugs. If a medical condition is revealed that could be causing your depression, treating that condition could resolve the problem. Additionally lifestyle changes should be pursued along with talk therapy before a person starts taking antidepressant drugs.

Will antidepressants work for you?

Once you try them, you’ll find out. There’s really no telling whether an antidepressant is going to work until you try it. This is like asking the question “What is the best antidepressant?” In reality, there is no universal utopian option. You must experiment and find out what works for you. For many people using antidepressants will work wonderfully and help them get through bouts of major depression.

For others, engaging in healthy activities like exercising, socializing, eating healthy, and psychotherapy will fix more than an antidepressant ever would. It is very important to understand that what works for you, may not work for someone else. So if you are prescribed Cymbalta and it works well, you cannot assume your best friend will have the same results if they try it. It may end up making them feel even more suicidal.

Additionally others may shun those who take antidepressants because something like exercise helped their symptoms. In this case, another person may have actually tried rigorous exercise and found that it truthfully didn’t help. Sometimes all the lifestyle changes in the world won’t matter if your genetics promote major depression. For this reason it is important to be empathetic to others dealing with this condition and realize that no one has the solution.

The person who is depressed must discover a solution on their own through lifestyle changes, natural antidepressants, medication trials, social changes, etc. It may take a lot of pain and suffering to find something that works, but many people are able to eventually figure how to live life and cope with their depression.

Verdict: Antidepressants are an effective treatment for major depression

Although not everyone will respond well to antidepressant treatment, these drugs have proven themselves better than most forms of therapy for treating major depression. If you need to utilize one of these drugs to help improve your depressive symptoms, you shouldn’t be afraid to do so. Don’t waste time reading other people’s horror stories on the internet and focus on doing what you can to improve your situation.

If you try making sensible lifestyle changes, seek help of a therapist, and still feel like you want to die, an antidepressant can be a great option.  Major depression isn’t some stint of feeling sad for a few days, it’s chronic, deep sadness that never seems to improve.  For some people with major depression, antidepressants are the single best treatment option.

The current drugs on the market provide more options than people had 10 years ago, 20 years ago, and significantly more options than people had 50 years ago. There are many types of antidepressants to chose from, and there are new antidepressants (2014) in development. Treatment for major depression may be an imperfect science, but it will continue to get better throughout our lifetime.

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