Does Cymbalta lose effectiveness over time? (3+ precautions)

This article will answer the question, “Does Cymbalta lose effectiveness over time?”. We will also talk about the factors which can decrease the effectiveness of Cymbalta along with the measures to use Cymbalta effectively.

Does Cymbalta lose effectiveness over time? 

Yes, Cymbalta can lose its effectiveness over time. Research studies have shown that antidepressants can lose their effectiveness when used for long-term treatment. (1) Individuals may develop tolerance to the drug, leading to a decreased effectiveness of the drug. 

Antidepressants work differently for each individual. Some may respond to the medication, while some may not. There are many reasons for an antidepressant to lose its effectiveness, such as concomitant use of medications, substance abuse, chronic mental illnesses, use of expired drugs, etc. 

You can say a drug is no longer effective when the symptoms it was treating relapse. If you notice worsening of your depression, anxiety or pain, seek medical attention. 

What does the research suggest? 

A clinical study evaluated the effectiveness of long-term Cymbalta (duloxetine) treatment of 1 year in which Cymbalta 80mg/day and 120mg/day were administered to the patients. The study concluded that Cymbalta was well-tolerated and effectively treated symptoms of depression in the long term. In a total of 1279 patients, 218 patients discontinued the treatment because of side effects and pregnancy. (2)

Another study was conducted on the long-term effectiveness, safety and tolerability of Cymbalta in treating fibromyalgia. The six-month research concluded that Cymbalata was effective in treating symptoms of fibromyalgia. (3) 

What happens if Cymbalta loses effectiveness over time? 

Cymbalta is an antidepressant which belongs to the group of serotonin-norepinephrine reuptake inhibitors (SNRIs), which increase serotonin, norepinephrine and dopamine levels by inhibiting their reuptake. An increase in these neurotransmitters helps improve mood, memory, attention and other cognitive functions. (4)

Cymbalta also acts on the neurons of the dorsal horn in the spine, which reduces the pain signals from reaching the brain, treating fibromyalgia and chronic pain. (4)

When Cymbalta loses effectiveness, it can cause a recurrence of fibromyalgia pain and worsen cognitive functioning. If you experience any reoccurrence of symptoms or if you notice worsening of your depression or anxiety, consult your healthcare professional immediately for further management. 

Get evaluated for any undiagnosed mental illness or any underlying health condition which can influence your symptoms. If you are not properly responding to your treatment, your physician may increase the dose of your drug or switch to another antidepressant. 

If Cymbalta is ineffective in treating your symptoms, you can consider alternative antidepressants such as: 

  • SSRI: fluoxetine, citalopram, paroxetine, sertraline. 
  • SNRI: venlafaxine, desvenlafaxine, milnacipran.
  • Tricyclic antidepressants: amitriptyline, desipramine, imipramine, nortriptyline.
  • Atypical antidepressants: bupropion, mirtazapine, trazodone, vilazodone. 

If you are taking Cymbalta to treat fibromyalgia, you can shift to other antidepressants or pregabalin, an anticonvulsant which has shown effectiveness in treating fibromyalgia. (5) You can also consider non-pharmacological therapies such as cognitive behavioural therapy and psychotherapy along with medication to help you treat your illness more effectively. 

What factors can contribute to the effectiveness of Cymbalta?

There are many reasons why Cymbalta can lose its effectiveness, causing relapse of symptoms such as: 

  • Tolerance: During long-term treatment, the drug attains a steady-state plasma concentration (the drug leaving the body equals the drug absorbed by the body); tolerance develops when the body becomes accustomed to constant medication dosage. Tolerance to the drug can be mitigated by increasing the dose of the drug.


  • Non-adherence: Not taking Cymbalta as prescribed by your physician may reduce its effectiveness by lowering the levels of the drug in the body. A sudden decrease in the level of the drug can cause discontinuation symptoms and worsen your condition. 


  • Severe conditions: If the mental illness progresses and becomes severe, the current dose of Cymbalta may not be effective. In a severe condition of mental illness, a high dose or a combination of antidepressant therapy is needed to mitigate the symptoms. 


  • Underlying conditions: Any pre-existing medical conditions that affect the kidneys and liver can influence how the body metabolizes and eliminates the drug, which can lead to decreased response. Treating any undiagnosed or misdiagnosed mental illness with Cymbalta can reduce its effectiveness in treating symptoms. 


  • Drug interactions: Cymbalta may interact with other drugs, such as amphetamines, aspirin, tramadol, alprazolam, etc., reducing its effectiveness and increasing the risk of side effects. 


  • Psychosocial factors: Stress can lead to fluctuations in neurotransmitters, which can affect mood and cognitive function. It is important to maintain a stress-free and healthy lifestyle along with drug therapy to treat your illness more effectively. 


  • Genetic factors: The enzymes responsible for drug metabolism and transportation may vary depending on genetics, which can influence the effectiveness of the medication. 

How to use Cymbalta safely and effectively? 

Cymbalta can be used safely and effectively by following a few simple tips:

  • Take Cymbalta every day as prescribed by your doctor.
  • Do not miss a dose of Cymbalta, as it can cause withdrawal symptoms. If you tend to forget to take a dose, set an alarm to ensure you take the dose on time. 
  • Store Cymbalta in a proper condition. Store it in a cool, dry place away from sunlight and moisture, as these factors can chemically degrade Cymbalta and render it ineffective.
  • Do not crush or chew the tablets, nor open the capsule before consuming.
  • Attend regular follow-ups to monitor your progress and for any necessary adjustments in your therapy.
  • Do not alter the course of your treatment without a physician’s guidance.
  • Look out for any unwanted side effects, suicidal thoughts and recurrence of symptoms.

In my opinion, as a pharmacist, with long-term treatment, one can develop tolerance to Cymbalta, leading to a reduction in its effectiveness. This can be managed by increasing the dose of Cymbalta or changing the drug to another antidepressant.

If your symptoms reappear and you notice any unwanted changes in your behaviour, consult your physician for proper management. 

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Mease PJ, Russell IJ, Kajdasz DK, Wiltse CG, Detke MJ, Wohlreich MM, Walker DJ, Chappell AS. Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia. InSeminars in arthritis and rheumatism 2010 Jun 1 (Vol. 39, No. 6, pp. 454-464). WB Saunders. Available from:


Dhaliwal JS, Spurling BC, Molla M. Duloxetine. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: 


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