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Long-Term Effects of SSRIs & SNRIs

Last Updated on December 9, 2022 by Diane Ridaeus

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

New information on the long-term effects of SNRIs and SSRIs is being discovered, though these drugs have been on the market for over a third of a century. New iterations of SSRIs and SNRIs continue to be released in Pied Piper fashion, especially as older patents expire.

The medical literature is still developing on using antidepressants for depression and other unwanted symptoms. Here, we’ll discuss published research as a service to anyone struggling with unresolved symptoms and who is curious about healthy ways to recover from long-term SSRI or SNRI effects. While it may seem a lot to digest, planning your recovery effectively could be greatly assisted by an enhanced understanding of the long-term effects of SNRIs and SSRIs.

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What are SSRI and SNRI Drugs?

These terms are acronyms (abbreviations) to handily describe the natural chemicals that these drugs target. SSRI stands for selective serotonin reuptake inhibitor. SNRI stands for serotonin and norepinephrine reuptake inhibitor. Serotonin and norepinephrine (adrenaline) are natural hormones that act as transmitters of signals between nerve cells. Neither SSRIs nor SNRIs can create more natural hormones. The role of these drugs is quite different than that, as will be explained below.

Serotonin molecules have a dampening effect. Norepinephrine molecules have a stimulating or activating effect. These natural chemicals interact with and regulate a vast number of systems and organs in the body. Billions of $ have been spent on drug advertising labeling SSRIs and SNRIs as “miracle drugs” or  “brain boosters,” which is oversimplified, and some would say blatantly misleading use of language. 

As Moncrieff et al point out in recent research published in the Journal of Molecular Psychiatry, a close examination of the assumption that “serotonin deficiency causes depression” driving the promotion of antidepressants, reveals the theory may have been cobbled together based on flawed animal studies, influenced by supposition, the possibility of omitted and “cherry-picked” drug trials, and clever word-play in advertising, rather than factual data.19,22,28,29

serotonin reuptake blockersIn actuality, most serotonin is found outside the central nervous system.17 Through an intricate and complex chain of reactions involving other neurochemicals as well, serotonin is involved in the operation and regulation of the heart, including heart rate, blood pressure, blood coagulation, and other cardiac manifestations. Serotonin is also involved in the reproductive system, the endocrine system (which regulates and monitors mood and emotions, growth, digestion, metabolism, and multiple organ regulation), and uncountable other vital functions in human health as well. Serotonin operates within a multi-level systems-wide template that is still not completely understood. Drugs cannot create more serotonin, but only accelerate the activation of these reserves, until they are exhausted.24,17,18,22

Norepinephrine is a form of adrenaline, a natural human hormone that accelerates certain cellular functions, including those that are related to the transmission of energy signals affecting the brain, the heart, and the entire body, via the central and sympathetic nervous systems. As an excitatory natural hormone in the body, it is associated with the “fight or flight” response. It is also associated with awareness, alertness, memory, learning, cognitive function, and emotional responses including excitement, fear, and paranoia. In dysregulation, adrenaline has been associated with positive symptoms or worsening symptoms of schizophrenia including hallucinations and psychosis.20,21

SSRIs and SNRIs are lab-created drugs, that block the transmission of natural neurotransmitters, causing a temporary build-up or concentration at the synapses that lie along the intricately designed nervous system. These captured natural hormones can remain active for only so long at which point the molecules degrade and are lost. The drug prevents these natural hormones from being recycled for reuse in the future as they were designed to do. But the drug interrupts normal hormone recycling, resulting in accelerated loss of these essential natural hormones.9

Whether one had or didn’t have a prior deficiency of these natural hormones, after long-term SSRI and SNRI use, results consistent with dysregulation and deficiency ARE observed, as researchers such as Moncrieff, Hussain, and countless others eloquently point out in their peer-reviewed work. It’s a bit like trying to keep your house lit with matchsticks. It might work for a while, but eventually, you’re going to run out of matches and be left in the dark. This loss of efficacy is associated with developed tolerance, which is when taking a drug does not produce the same effects as it once did. Like trying to make a withdrawal from an empty bank account, or stepping on the gas pedal of a car after it ran out of gas, drugs stop working after tolerance has developed. 8,9,19,21

The first-ever SSRI was fluoxetine, the one that ultimately became known as Prozac©, invented by a German chemist named Schmiegal at Eli Lilly. Schmiegal specialized in veterinary compounds to enhance animal growth and leanness. He was looking for an anti-obesity agent. One compound was found ineffective against obesity, but that blocked the reuptake of serotonin in sliced rat brains. It took 16 years for Lilly to find a home for it when a small trial on humans reported it had an antidepressant effect.26,27 From there, it was quickly catapulted to the top of the pharmaceutical drug pile, remaining there until the patent expired in 2001. Prozac was the first SSRI and copycat drugs soon followed such as Paxil©, Zoloft©, Lexapro©, Celexa©, Viibryd©, and Luvox©.23-25

The first-ever SNRI was the antidepressant Effexor, generic venlafaxine. Because of extreme nausea associated with the drug, an extended-release version, Effexor XR, soon replaced the original.24 Based on a similar template, SNRIs apparently cause a synaptic build-up of adrenaline AND serotonin molecules where they remain suspended until they eventually degrade and are lost. This was proposed to have an antidepressant effect. But there are other, especially long-term effects of SNRIs that are perhaps less well-known, and problematic to human health. A sampling of the long-term effects of SSRIs and SNRIs is detailed below.

What are the Long-Term Effects of SSRI and SNRI Drugs?

SSRIs and SNRIs replaced older antidepressants and were promoted as safer and with fewer side effects than earlier tricyclics, monoamines, and others that arose in drug labs from the previous century. Despite being promoted as safer than earlier antidepressants, the past 3 decades have revealed a concerning set of adverse effects that can result after long-term use of SSRIs and SNRIs. Since the known set of adverse effects in short-term trials may in fact linger during maintenance treatment, these have been included in the summary below. Due to the enormous variety of adverse effects associated with these 2 classes of drugs, a brief summary is provided below.4,5,10,12,13,19,22-25

Long-term effects of SSRIs and SNRIs can include:
  • long term effects snri ssri drugsSuicidality
  • Worsened depression
  • Mood dysregulation
  • Insomnia
  • Sexual dysfunction
  • Developed tolerance, dependence, and addiction
  • Discontinuation syndrome if the dosage is delayed or stopped
  • Gastrointestinal disorders
  • Movement and motor control disorders
  • Fetal injury
  • Cardiovascular events
  • Psychiatric symptoms
  • Eye damage
  • Other organ damage

Were the Long-Term Effects of SSRIs and SNRIs Known Before FDA Approval?

The short answer is NO. Pre-approval trials are typically short, not long-term. FDA approval has not historically required long-term safety trials. However, in a dramatic and positive move, in 2007 the FDA introduced more stringent requirements, backed by law, that post-market safety reports can be required to continue licensing a drug for commercial sale.16

Drug manufacturers are profit-driven, competitively speed-oriented, and have a speckled reputation when it comes to drug safety. The FDA’s role is one of control, regulation, and since 2007, continuous monitoring of both new and old drugs for consumer safety and efficacy. The FDA is tasked with approving drugs before they become accessible to the consumer, and over the longer horizon, making sure that postmarketing risks are reported and changes to how drugs are used safely can be implemented.1-3

antidepressant suicide riskSome of the most immediate adverse effects of SSRIs and SNRIs were clearly observed pre-approval, and include the heightened risk of suicide, especially notable in the under-25 population. While this adverse effect was observed before FDA approval, it took some years of heightened attention and public concern for drug regulators to mandate a black-box warning for suicide risk on every antidepressant drug sold legally in the US.

Other effects were not fully recognized for years after the introduction of these drugs to the general public, and definitely were not observed or reported in short clinical trials pre-approval. Typically, drug testing is weeks long, not years long so there can be a considerable lag between the time of approval, and the accumulation of post-market reports indicating the potential long-term risks of SSRIs and SNRIs.5

In the case of safety during pregnancy and breastfeeding, little to no information was available pre-approval. Where studies concerning fetal injury were done, only animal trials were included in safety trials. Human pregnancy safety trials are controversial and not encouraged for ethical reasons. However, an ever-growing body of case reports and hospital stats have provided raw data that some researchers have collated over the years and cited in published research studies. The FDA typically remains agnostic on recommendations for or against SSRI and SNRI use during pregnancy. Later studies, clinical case reports, and monitoring have shown a number of fetal risks associated with SSRIs and SNRIs. Despite accumulating evidence of safety concerns, the FDA remains ambiguous, only recommending a woman talk to her doctor for help in deciding whether or not to initiate or continue treatment with antidepressants during pregnancy or while breastfeeding.30-32

What are Antidepressants Prescribed to Treat?

Per the FDA drug labels, SSRIs and SNRIs are mainly licensed to treat major depression with some exceptions. The SNRI Fetzima (XR) is not FDA-approved for treating major depression but is only approved to treat fibromyalgia. The SNRI Effexor (XR) is approved to treat not only major depression, but also anxiety disorders and panic disorders. The SSRI Paxil is FDA-approved to treat major depression, anxiety disorders, panic disorder, plus PTSD, and OCD, which the label infers are disorders presumed to originate from low serotonin in the patient’s brain.23-25,36

Apart from the FDA-approved uses, a long list of off-label uses has developed, including eating disorders, menopausal-related symptoms, sleep disorders, chronic pain management, smoking cessation, and others. Fluoxetine (Prozac©), fluvoxamine (Luvox©), sertraline (Zoloft©), and escitalopram (Lexapro©) are approved for children. Off-label prescribing is not uncommon in the pediatric population.6,7,35

Are SSRIs & SNRIs Habit-forming?

When a drug produces effects that are “liked” or pleasurable, it is likely to become habit-forming. Antidepressants are largely devoid of likable effects, except perhaps in high-dose recreational use for stimulation effects as in some noradrenergic antidepressants. However, what is most prevalent is that a person may become habituated to taking an antidepressant to avoid unwanted effects of discontinuation rather than for any perceived pleasure-seeking intention.33,34

Discontinuation After Long-Term SSRI & SNRI Use

One of the most prevalent reported long-term effects of SSRIs and SNRIs is the discontinuation effects which can be incredibly harsh, especially without medical assistance and guidance. One should never stop antidepressants abruptly. As each drug’s label stipulates, a gradual cessation protocol is recommended to avoid harsh discontinuation effects.23-25,36

Brain zaps are a commonly reported phenomenon when the dosage of an SSRI or SNRI is delayed, cut, or stopped, and are commonly reported to occur at the half-life elimination point of the drug. This electrical sensation in the head, neck, spine, or other parts of the body is poorly understood but is frequently reported in discontinuation. The phenomenon can persist long after the drug has been stopped without adequate recovery and support.47

More details on safely discontinuing specific drugs can be found on our website by searching for “(drug name) + withdrawal” in the main search bar or get started easily by going to antidepressant withdrawal for hundreds of pages of information describing protocols that are used at Alternative to Meds for safe, gentle recovery from long-term SSRI and SNRI use.

Searching for the Root Causes of Unwanted Symptoms

root causes of addictionWhen a person is desperately seeking relief for unwanted symptoms, in the rush to find a solution, often taking time to search for root causes is overlooked entirely. Physicians are under time constraints and are often not trained in safer alternative treatments for their patients. We recommend thorough research of the types of treatments that are available that can help both in testing and diagnosing underlying causes of psychiatric symptoms like depression, and that can lead to an effective resolution in many cases, not relying on prescription medications for success. Some simple strategies follow, that are proven effective.

Diet modification can have life-changing effects. Testing for deficiencies can lead the way to eliminate symptoms that may be caused or augmented by low levels of certain nutrients. Eliminating foods and beverages that impair mental health and physical energy is a proven though often overlooked strategy.  Improvements in mood, regulating blood sugar levels, and other benefits may be felt nearly immediately by eliminating sugars, and caffeine, and reducing refined carbs. Adequate fresh fruits, vegetables, and quality protein are essentials that should be maintained for good health and energy levels. 

IMPORTANT NOTE: Tryptophan is the precursor for serotonin. While one is coming off an SSRI drug, tryptophan is available as a nutritional supplement that can help the body refurbish exhausted levels of serotonin. Please note that tryptophan supplements and foods high in tryptophan should be avoided while taking serotonergic drugs, as a life-threatening condition called serotonin syndrome (too much active serotonin) can result. Foods high in tryptophan including bananas, oats, cheese, bread, poultry, canned tuna, chocolate, and many others should be avoided unless guided by a medical professional who is working with you to taper off an SSRI. Testing (including testing for food allergies) is another tool that can greatly assist in planning the most helpful ways to modify the diet.37,46

Support for a healthy microbiome is essential for mental wellness. A compromised gut can create havoc both physically and mentally. Replenishing the gut flora can be accomplished by adding fermented foods like sauerkraut and yogurt, and taking probiotics daily. This strategy can be helpful before, during, and after a holistic detox program.39,40

Testing for the presence of neurotoxins is recommended. Toxins that can affect mental health include exposure to mercury, lead, cadmium, and the chemicals we are bombarded with in daily life from cleaning products, food additives, pesticides, and many others. Cleansing these from the body in safe and gentle ways can allow a remarkable resurgence of natural mental well-being.41,42

Improve the quality of sleep. Poor sleep is associated with a number of mental and emotional areas of dysfunction and is especially prevalent in depressed persons. Practice good sleep hygiene to give you and your body the best start to each day. This can include removing electronics from the bedroom, proper ventilation, light-blocking drapery, a comfortable eye mask, noise-blocking earplugs, toxin-free sheets and pillowcases, and a comfortable non-toxic mattress and pillow. There are natural supplements that can also aid sleep without next-day drowsiness or mental fog.43

Recovery from the Long-term Effects of SSRI and SNRIs at Alternative to Meds Center

sedona holistic detox recoveryAlternative to Meds Center uses a foundational approach of orthomolecular medicine, environmental medicine, and a host of holistic evidence-based therapies in helping our clients recover from unwanted symptoms, and from the consequences of drug therapy that didn’t deliver the successful outcome one was seeking. Holistic detox is part of the services we offer, under medical supervision and attentive care by over 40 licensed professionals. Neurotoxin removal and neurotransmitter rehabilitation are fundamental parts of getting well, and the results can be life-changing. Counseling is another recommended treatment avenue, and we offer CBT and many other genres including Equine therapy, another highly popular segment of the program.44,45

We recommend reviewing all the treatments and protocols used in our treatment facility to get a better understanding of our programs. Find out how we have been able to help so many clients over the past nearly 20 years to extricate themselves from the grip of pharmaceuticals that just aren’t helping as hoped.  As you will see, we are evidence-based but you will also find us compassionate, and very much people-oriented. The peer support and caring nature of our staff create a friendly and warm-hearted atmosphere that is highly conducive to healing. 

Then please give us a call and ask any other questions you may have about our program, including insurance queries, and estimates for the length of the program, and let us tell you about our beautiful facility. We are here to help you in your decision-making process about your next step forward. Our program has been forged using the best technologies, the best and most compassionate staff, and decades of experience, successfully helping thousands of clients recover from the long-term effects of SSRIs and SNRIs.

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Originally Published December 9, 2022 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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