Extended antidepressant use creates physical dependence

Summary: Long-term use of antidepressants can create physical dependence and severe withdrawal symptoms for patients looking to stop their treatment. Patients who quit their medication often experience Antidepressant Discontinuation Syndrome, which results in flu-like symptoms, insomnia, nausea, and other symptoms associated with withdrawal.

Source: American Osteopathic Association

Patients who have taken antidepressants for years should consider coming off the medication. However, researchers say they will likely face difficult and even dangerous withdrawal symptoms due to a physical dependence.

The best process is to follow a tapering schedule while consulting with a physician, according to research in The Journal of the American Osteopathic Association. Stopping medication outright is almost never advisable.

“I understand that many people feel safe in that their depression or anxiety is continuously managed by medication. However, these are mind-altering drugs and were never intended as a permanent solution,” says Mireille Rizkalla, PhD, Assistant Professor, Department of Clinical Integration at Midwestern University Chicago College of Osteopathic Medicine, and lead author on this research. “Once the patient’s depression or anxiety has been resolved, the physician should guide them toward discontinuation, while providing non pharmacologic treatments to help them maintain their mental health.”

Hard to quit

Patients who stop taking their medication often experience Antidepressant Discontinuation Syndrome (ADS), which includes flulike symptoms, insomnia, nausea, imbalance, sensory disturbances often described as electric shocks or “brain zaps”, and hyperarousal.

Older, first-generation antidepressants often come with additional risks for more severe symptoms, including aggressiveness, catatonia, cognitive impairment, and psychosis. Discontinuing any antidepressant also carries a risk for gradual worsening or relapsing of depression and anxiety, as well as suicidal thoughts.

Indefinitely medicated

A recent report from the CDC said a quarter of people taking antidepressants had been using them for a decade or more. Rizkalla says this data makes the case that patients and physicians are overly reliant on medication without concern for long-term consequences.

This shows a man looking out of a window
Patients who stop taking their medication often experience Antidepressant Discontinuation Syndrome (ADS), which includes flulike symptoms, insomnia, nausea, imbalance, sensory disturbances often described as electric shocks or “brain zaps”, and hyperarousal. Image is in the public domain.

“I think we have a real problem with patient care management, when it comes to prescribing antidepressants,” says Rizkalla. “We tend to put patients on an SSRI and more or less forget about them.”

She adds that, while relatively safe, antidepressants still carry side effects, including weight gain, sexual dysfunction and emotional numbing. She also urges caution as the evidence for antidepressant risk factors is based on short-term usage, and says there are no sufficient longitudinal studies on the neurologic impact of taking antidepressants for decades.

Rizkalla and her coauthors included the following tapering schedule for varying classes of antidepressants. However, she insists patients consult their physician before and throughout the process to monitor their symptoms and progress.

About this neuroscience research article

American Osteopathic Association
Media Contacts:
Jeff Brennan – American Osteopathic Association
Image Source:
The image is in the public domain.

Original Research: Open access
“Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem”. Mireille Rizkalla, PhD; Bryan Kowalkowski, OMS III; Walter C. Prozialeck, PhD.
The Journal of the American Osteopathic Association doi:10.7556/jaoa.2020.030.


Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem

Antidepressants are a diverse group of medications commonly used as front-line agents for the treatment of various forms of depression. However, many of these medications are also used to manage other conditions, such as obsessive-compulsive disorders, generalized anxiety disorders, eating disorders, neuropathic pain syndromes, and chronic pain syndromes. Given the widespread use of antidepressants, physicians may be driven by an overestimated consideration of potential benefits, while appraisal of adverse effects are, by comparison, often overlooked.

Antidepressants are typically classified as either first or second generation. The first-generation antidepressants include tricyclics, a tetracyclic agent, and the monoamine oxidase inhibitors (MAOIs). Even though they are efficacious in the management of depression and other conditions (eg, anxiety disorders, eating disorders), use of the first-generation agents is often complicated by adverse effects, toxicity in overdose situations, and numerous drug-drug and drug-food interactions.1 Second-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and a variety of other agents, such as trazadone, bupropion, and mirtazapine. These agents generally have better side effect profiles and are far less likely to cause death in cases of overdose.

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