Does Cymbalta make you more depressed? (8 alternatives)

In this brief article, we will discuss whether Cymbalta makes you more depressed. We will delve into the impact of Cymbalta on mood and examine the factors influencing its mood-altering effects. Additionally, alternative approaches will be discussed in case Cymbalta exacerbates feelings of depression.

Does Cymbalta make you more depressed?

Cymbalta may make you more depressed. The impact of Cymbalta on mood can vary among individuals. While Cymbalta is primarily prescribed for depression and anxiety, Cymbalta may lead to mood changes and for some individuals, it could even worsen feelings of depression.

Cymbalta functions by elevating the levels of serotonin and norepinephrine in the brain. These neurotransmitters play a significant role in regulating mood. For the majority of individuals, Cymbalta effectively alleviates symptoms of depression, resulting in enhanced mood, increased energy levels and overall well-being.

Nevertheless, Cymbalta has the potential for worsening depression. In some cases, Cymbalta may initially worsen depression symptoms, especially during the first weeks of treatment. (1)

Individuals with a history of severe depression or suicidal thoughts may face an elevated risk of exacerbated symptoms while on Cymbalta. The effects of Cymbalta can be complex and vary depending on various factors.

What are the effects of Cymbalta on mood?

Although Cymbalta is an antidepressant that is designed to improve mood by affecting neurotransmitters in the brain, some individuals may experience negative effects on mood. The effects of Cymbalta on mood include (2):

Positive effects on mood 

Reduced symptoms of depression: Cymbalta is effective in alleviating various symptoms of depression, such as sadness, hopelessness, fatigue and difficulty concentrating.

Improved mood and energy levels: The increased levels of serotonin and norepinephrine can lead to a more optimistic perception, increased energy, hyperactivity and enhanced motivation.

Reduced anxiety: Cymbalta also has anxiolytic properties. It can help individuals manage anxiety symptoms like nervousness, restlessness and worry.

Improved sleep: By regulating mood and reducing anxiety, Cymbalta can promote better sleep quality, which can contribute to improved mood and overall well-being.

Potential negative effects on mood

Initial worsening of depression: During the initial weeks of treatment, some individuals may experience a worsening of their depression symptoms. This is typically temporary and resolves as the body adapts to the medication.

Heightened anxiety: Although Cymbalta is intended to help with anxiety management, paradoxically, it can exacerbate anxiety in certain instances.

Irritability and agitation: Cymbalta can sometimes cause irritability and agitation, which can negatively impact mood.

Emotional blunting: Cymbalta can lead to a feeling of emotional numbness. Some individuals may experience a reduced ability to feel emotions while taking Cymbalta.

Suicidal thoughts: Although rare, Cymbalta has been associated with an increased risk of suicidal thoughts. (3)


What does the research suggest?

The research on Cymbaltta and its potential to worsen depression is complex and nuanced. Some individuals experience a temporary worsening of their depression symptoms shortly after starting Cymbalta. This phenomenon is known as Cymbalta-related acute dysphorias. Dysphoria can manifest as intense agitation, anxiety and increased suicidal thoughts.

One case study highlights the potential risk of rapid dosage increases with Cymbalta. Mrs. M, 73 years old, initially tolerated 20 mg/day, but she developed an acute and intense dysphoric episode after several days of a dosage increase to 40 mg.

Describing it as the worst depression she had ever experienced, she promptly discontinued the medication. Within 48 hours, her dysphoric symptoms were completely resolved.(4)

Additionally, an increased risk of suicidal thoughts and behavior is a documented side effect of Cymbalta, particularly in young adults and adolescents. Studies have shown an increased risk during the initial weeks of treatment and at dosage changes.

A clinical trial investigating Cymbalta’s efficacy showed a concerning high dropout rate, with 20.3% of patients discontinuing treatment due to lack of effectiveness and 59.5% due to experiencing adverse events. (3)



What factors can influence individual responses to Cymbalta?

Factors influencing the effects of Cymbalta on mood include: 

  • Individual sensitivity: Each person responds differently to medications, and the effect of Cymbalta on mood can vary significantly between individuals. Variations in an individual’s biochemistry can contribute to different responses to the medication.


  • Genetics: Genetic variations can impact how individuals metabolize and respond to Cymbalta and other medications.


  • Underlying medical conditions: Existing medical conditions, such as thyroid problems or substance abuse, can interact with Cymbalta. This can affect Cymbalta’s efficacy and tolerability.


  • Dosage: The specific dosage of Cymbalta can influence both its effectiveness and the likelihood of side effects.


  • Use of other medications: Taking Cymbalta with other medications can influence its effects on mood, potentially causing side effects or interactions.


  • Psychosocial factors: Stress, lifestyle and environmental factors can also play a role in how someone responds to Cymbalta.



What to do if Cymbalta makes you more depressed?

If Cymbalta makes you feel more depressed, it’s essential to take the following steps:

  • Contact your healthcare provider: Report the changes in your mood to your healthcare provider promptly. Your healthcare provider can assess your situation and determine the best course of action to take.


  • Avoid abrupt changes: Do not stop taking Cymbalta suddenly without consulting your healthcare provider, as abrupt discontinuation can lead to withdrawal symptoms.


  • Consider alternative options: Your healthcare provider may suggest trying a different antidepressant or exploring additional therapeutic approaches.


  • Monitor potential side effects: Keep track of any other side effects besides worsening depression you may be experiencing. Cymbalta can cause anxiety, insomnia and sexual problems. Make sure to report any side effects to your healthcare provider for a comprehensive evaluation. 


  • Dosage adjustment: Your healthcare provider may recommend adjusting your Cymbalta dosage to minimize side effects. The higher the dose, the more likely you are to experience side effects.


What are alternative approaches available if Cymbalta makes you more depressed?

If Cymbalta seems to worsen depression or cause adverse effects, it’s crucial to consult your healthcare provider. They may consider alternative approaches, such as (5):

  • Medication adjustment: Your healthcare provider may adjust the dosage of Cymbalta to see if a lower or higher amount is more effective for you.


  • Switching medications: Your doctor may consider different antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and atypical antidepressants. Alternative antidepressants can include fluoxetine, citalopram, sertraline, bupropion and mirtazapine.


  • Combining medications: In some cases, combining Cymbalta with another medication, such as a mood stabilizer or antipsychotic, might be helpful. However, your healthcare provider should make a thorough evaluation before combining medications to avoid potential interactions.


  • Psychotherapy: This can be a very effective way to address the underlying causes of your depression and develop coping mechanisms. There are different types of therapy, such as cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), that can be helpful complementary treatments for depression.


  • Lifestyle changes: Eating a healthy diet, getting regular exercise and getting enough sleep can all improve your mood and mental health.


  • Brain stimulation therapies: Treatments like electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) may be considered for severe depression that has not responded to other treatments.


  • Mind-body techniques: Explore mindfulness, meditation or yoga which may help manage depressive symptoms.


  • Supplements: Consult your healthcare provider about the use of supplements. There is some evidence that certain supplements, such as omega-3 fatty acids and vitamin D, may help improve mood in people with depression.




In conclusion, although Cymbalta is an effective treatment for depression and anxiety, it can paradoxically worsen depressive symptoms and significantly reduce the quality of life. In my opinion, Cymbalta can be a mood-booster for some, a neutral for others, and even a mood-wrecker for a few. 

Make sure to report all your concerns and side effects immediately to your healthcare provider. Your healthcare provider can assess your situation and take the best course of action based on your individual needs.


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SYSTEMATIC REVIEW article, Front. Psychiatry, 23 October 2020,Sec. Psychopharmacology,Volume 11 – 2020.


Sansone RA, Sansone LA. Duloxetine-related acute dysphoria. Psychiatry (Edgmont). 2007 Nov;4(11):65-8. PMID: 20428305; PMCID: PMC2860520.,doses%20above%2060mg%20per%20day.


Dunlop BW, LoParo D, Kinkead B, Mletzko-Crowe T, Cole SP, Nemeroff CB, Mayberg HS, Craighead WE. Benefits of Sequentially Adding Cognitive-Behavioral Therapy or Antidepressant Medication for Adults With Nonremitting Depression. Am J Psychiatry. 2019 Apr 1;176(4):275-286.

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