What do when your antidepressants stop working

Samir Kadri
Author: Samir Kadri Medical Reviewer: Morgan Blair Last updated:

From a pharmacological perspective, treatment for depression and other mental health conditions typically begins with being prescribed antidepressants.

Every person responds to antidepressants differently, but after an assessment with your doctor and perhaps some trial and error with various medications, you will typically find an antidepressant that alleviates your symptoms.

However, in some cases, your antidepressants may stop being effective. It is common for an antidepressant that once worked well to lose its effectiveness. Symptoms return for roughly a third of people using antidepressants. [1]

In some cases, people will not respond to antidepressants at all, with a 2015 study showing that up to two-thirds of people did not achieve remission following a course of antidepressants. [2]

What do when your antidepressants stop working

What to do if your antidepressants aren’t working

It is essential you talk with your healthcare provider regularly throughout your course of antidepressants. If you are still experiencing symptoms of the mental health condition you were prescribed antidepressants for, there are steps you can take to achieve a better outcome.

Your doctor may choose to adjust your dose or change your medication. For example, if a selective serotonin reuptake inhibitor (SSRI) has proven ineffective, your doctor may choose to switch you to an atypical antidepressant.

It is worth noting that antidepressants take roughly 4-8 weeks to work, and up to 12 weeks for full effectiveness. It is important to give the medication time to function before deciding it is ineffective. [4]

If your antidepressant was previously effective but your symptoms have returned, you may be experiencing antidepressant tachyphylaxis. [3] For some, depression can be a recurrent, lifelong illness and patients may experience many depressive episodes in their lifetime. The rate of tachyphylaxis is estimated to be around 25%. [3]

Tachyphylaxis can be managed by your doctor, who can guide you through the gradual tapering of your antidepressants. It is essential you do not stop or alter a course of antidepressants suddenly, even if you believe they are no longer effective. This can lead to severe withdrawal symptoms.

In addition to the tapering-off process, your doctor may alter your prescription, switch you to a different class of antidepressant, suggest self-care tips, or recommend psychotherapy to go alongside your pharmacological treatment.

It can feel immensely frustrating when medication is not working as you feel it ought to. Having a strong support network can be helpful in managing mental health conditions. Reach out to friends, family, or support groups to share your feelings and experiences.

Why are my antidepressants not working?

There are various reasons why antidepressants may lose their effectiveness. Once you and your doctor have ascertained the exact cause of your symptoms returning, you’ll be able to make the necessary changes to improve your treatment.

Below are some reasons your antidepressants may have stopped working:

Drug or alcohol use

Illicit drug or alcohol use can cause mood imbalances which can render your antidepressants ineffective. [1]

Secondary health condition

If you’ve developed a separate health condition, such as diabetes or Alzheimer’s disease, this may have brought on symptoms of depression. So, it wouldn’t be a case of your old symptoms returning, rather there would be a different disorder that now requires treatment.


A stressful development at home or in your professional life can result in a mood alteration that impacts the effectiveness of your antidepressant treatment. [1]

Starting a new medication

The interaction between antidepressants and other medications can impact the effectiveness of antidepressants. [1] Always consult your doctor before taking any new medication whilst on a course of antidepressants.


Pregnancy causes your weight and blood volume to increase, which can lead to you requiring a higher dose of antidepressant. Consult your doctor if you are on antidepressants and planning a pregnancy as some are safer than others. [1]

Bipolar disorder

Occasionally, the ineffectiveness of an antidepressant can be explained by the up-and-down nature of bipolar disorder. [4] Antidepressants can exacerbate bipolar symptoms.

Alternatives to antidepressants

If you do not want to take antidepressants, there are numerous alternative treatments you can try. Below is a list of options:

Talk therapy

Talk therapy, such as cognitive behavior therapy (CBT), is often the recommended course of treatment for treating depression and numerous other mental health conditions. [5]

Therapy involves identifying negative thought patterns and gradually learning to respond to them more healthily. Therapy may be offered alongside, or in conjunction, with antidepressants. [5]


Studies show that mindfulness can be helpful in the management of depression. [5] Mindfulness encourages practitioners to give their full attention to the present moment. There are now types of mindfulness-based cognitive therapy that can be effective in managing depression. [5]

Other therapies

A host of therapies, including art therapy, ecotherapy, and aromatherapy, may be helpful for people seeking to manage symptoms.


Even if you take antidepressants or are seeking alternative treatment, self-care is still an effective addition to your treatment. You can implement the following steps to look after your health: [5]

  • Be more active: Physical activity can boost your mood, increase energy levels, and get you out in the real world.
  • Diet: Eat a balanced and nutritious diet to make you feel as good as possible. Make sure you are well hydrated too.
  • Get enough sleep: Establishing a regular sleep routine can be difficult, but good quality sleep is fundamental to good mental health. Work with your doctor on implementing a healthy sleep regime.
  1. Nestadt, P. (2023). Why Aren’t My Antidepressants Working? Www.hopkinsmedicine.org. https://www.hopkinsmedicine.org/health/wellness-and-prevention/why-arent-my-antidepressants-working
  2. Ionescu, D. F., Rosenbaum, J. F., & Alpert, J. E. (2015). Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience, 17(2), 111–126. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518696/
  3. Targum, S. D. (2014). Identification and Treatment of Antidepressant Tachyphylaxis. Innovations in Clinical Neuroscience, 11(3-4), 24–28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008298/
  4. National institute of Mental Health. (2023, September). Depression. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/depression
  5. MIND. (2020, September). Alternatives to antidepressants. Www.mind.org.uk. https://www.mind.org.uk/information-support/drugs-and-treatments/antidepressants/alternatives-to-antidepressants/
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Samir Kadri
Author Samir Kadri Writer

Samir Kadri is a medical writer with a non-profit sector background, committed to raising awareness about mental health.

Published: Oct 24th 2023, Last edited: Oct 24th 2023

Morgan Blair
Medical Reviewer Morgan Blair MA, LPCC

Morgan Blair is a licensed therapist, writer and medical reviewer, holding a master’s degree in clinical mental health counseling from Northwestern University.

Content reviewed by a medical professional. Last reviewed: Oct 24th 2023