Can I Develop A Tolerance To My Antidepressants?

Antidepressants are essential medications for millions of people managing mental health conditions like major depressive disorder, anxiety disorders, and other mood disorders. When they work well, these medications can dramatically improve quality of life by reducing symptoms and helping people function better in their daily lives. However, research shows that antidepressants don’t always maintain their effectiveness over time. Some people find that a medication that worked well for months or even years gradually becomes less effective, and their symptoms begin returning despite continuing to take the same dose.

This phenomenon is known as antidepressant tolerance, and doctors sometimes call it antidepressant tachyphylaxis (ADT), breakthrough depression, or colloquially, the “poop-out effect.” When tolerance develops, the brain adapts to the presence of the medication, requiring higher doses to achieve benefits.

What Is Antidepressant Drug Tolerance?

Tolerance is a change in the body’s response to a drug as it’s repeatedly used over time. For instance, feeling weaker drug effects after taking the same dose. Research shows that some common antidepressants can become less effective over time, at least in part due to the potential development of drug tolerance.

What Else Can Make Antidepressants Stop Working?

Several factors, in addition to drug tolerance, can impact how effective a drug continues to be for treating depressive symptoms, or anxiety symptoms.

Other contributing factors may include:

• missing doses
• stopping your medication
• beginning a new medication/supplement
• alcohol consumption
• drug abuse
• age
• stress
• undiagnosed bipolar disorder
• treatment-resistant depression
• other medical conditions

If you feel a relapse of symptoms, such as worsening mood or instability, it may be worthwhile to talk to your doctor about your treatment options.

Signs Of An Antidepressant Tolerance

The speed at which tolerance develops varies from person to person and depends on factors like the specific medication, individual brain chemistry, and overall health. Paying attention to changes in mood and mental health symptoms is crucial for catching tolerance before depression becomes severe again. Tolerance to antidepressants can develop over time through long-term use, or very rapidly in some cases. The primary sign of this is a depression relapse.

Signs of this may include:

• new or worsening depression
• thoughts of self-harm or suicide
• increased anxiety or panic
• irritability
• other symptoms of depression (e.g. fatigue)

If you notice any of these symptoms returning or worsening while taking your antidepressant as prescribed, don’t ignore them or assume they’ll pass on their own. Contact your doctor or mental health provider right away to discuss what you’re experiencing. It’s critical to seek immediate help if you’re having thoughts of self-harm. You can call 988 (the Suicide and Crisis Lifeline) or go to the nearest emergency room.

Which Antidepressants Cause Tolerance?

It is possible to develop tolerance to a number of antidepressant medications, although some drugs may be more or less likely to cause tolerance than others.

Examples of antidepressant tolerance include:

• Zoloft (sertraline) tolerance
• Prozac (fluoxetine) tolerance
• Paxil (paroxetine) tolerance
• Wellbutrin (bupropion) tolerance
• Tofranil (imipramine) tolerance
• Elavil (amitriptyline) tolerance
• Effexor (venlafaxine) tolerance
• trazodone tolerance
• Pamelor (nortriptyline) tolerance

Tolerance can potentially develop with any antidepressant, regardless of its class. SSRIs like Zoloft, Prozac, and Paxil are frequently reported, possibly because they’re widely prescribed. However, tolerance also occurs with SNRIs like Effexor, atypical antidepressants like Wellbutrin, and older tricyclics like Elavil and Tofranil. Developing tolerance doesn’t mean the medication was the wrong choice, it’s simply a potential side effect of long-term use that affects some people.

How Tolerance To Antidepressants Develops

The way that the body responds to antidepressants can vary from person to person. That is, not everyone who takes a certain drug may experience weaker effects over time.

Metabolic Tolerance

With most drugs, tolerance builds as the body adapts to the presence of the drug in your system. The way that your body metabolizes the drug can change. For instance, your body may metabolize the drug faster, leading to metabolic tolerance.

Decreased Sensitivity

Another possible explanation for the buildup of tolerance with antidepressant use is that the receptors in your brain become less sensitive to the drug over time.

Acute Tolerance

It is common for tolerance to develop with a wide range of drugs, including prescription opioids and benzodiazepines, following at least several weeks of regular use. But tolerance can also develop very rapidly over a short period, research shows, particularly with antidepressants. This is known as acute tolerance or rapid tolerance.

Negative Side Effects Of Antidepressant Tolerance

Antidepressant tolerance is not dangerous by itself. But for people with severe depression, it may cause a worsening, or return, of debilitating physical or mental health symptoms.

Potential side effects of tolerance include:

• thoughts of suicide
• urges to self-harm
• severe depression
• unstable mood
• increased anxiety or panic attacks
• intense irritability or anger
• loss of interest in activities once enjoyed
• social withdrawal and isolation
• difficulty concentrating or making decisions
• extreme fatigue or lack of energy
• changes in sleep patterns (insomnia or sleeping too much)
• changes in appetite or weight
• feelings of hopelessness or worthlessness
• physical symptoms like headaches or body aches
• inability to function at work or school
• strained relationships with family and friends

Tolerance can also be a risk factor for self-medication. That is, increasing your dosage on your own or turning to other drugs to relieve distressing symptoms.

Tolerance And Drug Abuse

When antidepressants lose their effectiveness, some people may turn to harmful coping mechanisms in an attempt to manage their returning symptoms. This is especially true for individuals who were using psychiatric medications to control depression, anxiety, or other mental health conditions. Without proper medical intervention, developing tolerance to antidepressants can become a dangerous turning point that leads to self-medication through alcohol or drug use. People may drink heavily to numb emotional pain, experiment with illicit drugs seeking relief, or misuse other prescription medications in ways not intended by their doctors.

Warning signs that someone may be battling drug or alcohol abuse alongside mental health issues include unexplainable mood swings, heavy or frequent drinking, using illegal drugs, dramatic changes in physical appearance or personal hygiene, engaging in risky or dangerous behaviors, and regularly missing work or school without explanation. If you notice these signs in yourself or a loved one it’s important to seek professional help immediately. Dual diagnosis treatment programs specialize in addressing both mental health disorders and substance abuse simultaneously, providing services that tackle both issues rather than treating them separately.

What To Do If You Develop A Tolerance To Antidepressants

Antidepressant efficacy can wane over time for a number of reasons. If this does happen to you, or a loved one, the first thing to do is contact your healthcare provider. Your prescribing clinician can offer personalized guidance for possible solutions or alternatives in order to ensure that your needs are met.

What this may involve:

• adjusting your dosage
• tapering or weaning off your current antidepressant
• looking at other possible causes (e.g. increased stress)
• adding or starting a new medication
• reassessing your initial diagnosis
• considering other behavioral health treatments (e.g. psychotherapy)

For drug abuse, professional treatment in a drug treatment program, or substance use counseling, may be recommended.

Antidepressant Tolerance FAQs

Get answers to frequently asked questions about antidepressant treatment and tolerance.

❓ Which Types Of Antidepressants Can Cause Tolerance?

✔️ Tolerance can develop through the use of many types of antidepressants.

This includes:

• monoamine oxidase inhibitors (MAOIs)
• tricyclic antidepressants (TCAs)
• selective serotonin reuptake inhibitors (SSRIs)
• serotonin and noradrenaline reuptake inhibitors (SNRIs)

❓ Is Antidepressant Tolerance The Same As Dependence?

✔️ No. Drug dependence can cause you to go through withdrawal (e.g. shakiness, nausea, sweating, headaches) if you suddenly reduce or stop your drug use.

Tolerance, on the other hand, does not cause withdrawal. It is simply a change in your body and brain’s response to a drug.

❓ Is Antidepressant Tolerance A Sign Of Addiction?

✔️ Antidepressants are not generally considered addictive. Addiction, unlike tolerance, is a condition that can require intensive treatment to overcome.

With other drugs, tolerance can be a sign of addiction if someone’s tolerance for a drug is very high, and they are engaging in harmful drug use behaviors.

❓ How Long Does It Take To Develop A Tolerance To Antidepressants?

✔️ The amount of time it takes for tolerance to develop can vary. For some, this can occur over a short period of time. For others, this may occur over months or years.

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Written by the Addiction Resource Editorial Staff