What is the difference between duloxetine (Cymbalta) and fluoxetine (Prozac)?

From the Guidelines

Duloxetine and fluoxetine have different mechanisms of action, with duloxetine being a serotonin-norepinephrine reuptake inhibitor (SNRI) and fluoxetine being a selective serotonin reuptake inhibitor (SSRI), which affects their efficacy in treating various conditions, including depression, anxiety, and pain. When considering the treatment of depressive disorders, the choice between duloxetine and fluoxetine should be based on the patient's specific symptoms and needs.

• Duloxetine is effective for depression, anxiety, fibromyalgia, and certain types of chronic pain, as it increases both serotonin and norepinephrine levels in the brain 1.
• Fluoxetine is commonly used for depression, obsessive-compulsive disorder, panic disorder, and bulimia, primarily increasing serotonin levels. In terms of efficacy, there is no significant difference between duloxetine and fluoxetine in treating anxiety associated with major depressive disorder (MDD), as shown in several fair-quality head-to-head trials 1. However, duloxetine may be more effective for managing pain, as it has been shown to have the same response rate as paroxetine in patients with MDD and pain 1. It is essential to consider the side effect profiles of both medications, as duloxetine is more likely to cause nausea, dry mouth, and increased blood pressure, while fluoxetine more commonly causes insomnia, nervousness, and sexual dysfunction. Ultimately, the choice between duloxetine and fluoxetine should be based on the individual patient's needs and medical history, taking into account the potential benefits and risks of each medication.

From the FDA Drug Label

1. Clinical Pharmacology 12.1 Mechanism of Action Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. DESCRIPTION Prozac® (fluoxetine capsules, USP and fluoxetine oral solution, USP) is a psychotropic drug for oral administration.

The main difference between duloxetine and fluoxetine is their mechanism of action and pharmacological profile.

• Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake, and a less potent inhibitor of dopamine reuptake.
• Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), but its exact mechanism of action is not fully described in the provided drug labels. Key differences include:
• Dual action: Duloxetine has a dual action on both serotonin and norepinephrine, whereas fluoxetine primarily acts on serotonin.
• Reuptake inhibition: Duloxetine inhibits the reuptake of serotonin, norepinephrine, and to a lesser extent, dopamine, whereas fluoxetine is more selective for serotonin reuptake inhibition. No direct comparison of the two drugs can be made based on the information provided in the labels 2, 2, and 3.

From the Research

Difference between Duloxetine and Fluoxetine

• Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), neuropathic pain, fibromyalgia, and stress incontinence urinary 4.
• Fluoxetine, on the other hand, is a selective serotonin reuptake inhibitor (SSRI) commonly used to treat depression, anxiety disorders, and other conditions.
• A systematic review comparing duloxetine with other antidepressants, including fluoxetine, found no statistically significant differences in efficacy between duloxetine and fluoxetine 5.
• However, the review noted that duloxetine may have a higher rate of dropouts due to adverse events compared to some SSRIs, such as escitalopram 5.
• Another study found that duloxetine was effective in the treatment of GAD, with a similar efficacy profile to venlafaxine, another SNRI 6.
• In terms of mechanism of action, duloxetine inhibits the reuptake of both serotonin and norepinephrine, whereas fluoxetine primarily inhibits the reuptake of serotonin 7.

Efficacy and Safety

• Duloxetine has been shown to be effective in the treatment of MDD, GAD, and other conditions, with a favorable safety profile 4, 8, 7.
• Fluoxetine has also been shown to be effective in the treatment of depression and anxiety disorders, with a generally well-tolerated safety profile.
• However, the safety and efficacy of duloxetine and fluoxetine may vary depending on the individual patient and the specific condition being treated.

Comparison with Other Antidepressants

• A systematic review comparing duloxetine with other antidepressants found that duloxetine did not provide a significant advantage in efficacy over other antidepressants, including fluoxetine 5.
• However, the review noted that duloxetine may have a higher rate of adverse events compared to some SSRIs, such as paroxetine 5.
• Another study found that duloxetine was effective in the treatment of GAD, with a similar efficacy profile to venlafaxine, another SNRI 6.