From the Guidelines
Cymbalta (duloxetine) works by increasing the levels of two important neurotransmitters in the brain: serotonin and norepinephrine, which helps improve mood, reduce anxiety, and decrease pain signals. It belongs to a class of medications called serotonin-norepinephrine reuptake inhibitors (SNRIs) 1. When these neurotransmitters are released in the brain, they normally get reabsorbed back into nerve cells. Cymbalta blocks this reabsorption process, allowing serotonin and norepinephrine to remain active in the brain for longer periods.
Key Points
- Cymbalta is typically prescribed at doses ranging from 30 to 60 mg once daily for depression and anxiety disorders, and 60 mg daily for chronic pain conditions 1.
- It may take 2-4 weeks to experience the full benefits.
- Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, increased sweating, and dizziness 1.
- These effects often improve over time as your body adjusts to the medication.
- Cymbalta should not be stopped abruptly as this can cause withdrawal symptoms; dosage should be gradually reduced under medical supervision when discontinuing treatment.
Mechanism of Action
The mechanism of action of Cymbalta involves the inhibition of the reuptake of serotonin and norepinephrine, which are two important neurotransmitters in the brain 1. This inhibition leads to an increase in the levels of these neurotransmitters, which in turn helps to improve mood, reduce anxiety, and decrease pain signals.
Clinical Evidence
Clinical trials have shown that Cymbalta is effective in reducing pain associated with diabetic peripheral neuropathy 1. The efficacy of Cymbalta has been confirmed in several clinical trials, with doses of 60 or 120 mg/day showing significant pain reduction 1. The number needed to treat (NNT) to achieve at least 50% pain reduction was 4.9 for 120 mg/day and 5.2 for 60 mg/day 1.
From the FDA Drug Label
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. Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake.
Duloxetine works by potentiation of serotonergic and noradrenergic activity in the central nervous system (CNS). The main mechanisms of action are:
- Inhibition of neuronal serotonin reuptake
- Inhibition of neuronal norepinephrine reuptake
- Less potent inhibition of dopamine reuptake 2
From the Research
Mechanism of Action
- Cymbalta, also known as duloxetine, is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS 3, 4, 5.
- It works by selectively inhibiting the serotonin (5-HT) and norepinephrine (NE) transporters (5-HTT and NET, respectively) 3, 6.
- This inhibition increases the levels of serotonin and norepinephrine in the brain, which helps to improve mood, reduce anxiety, and relieve pain 3, 4, 7.
Pharmacokinetics
- Duloxetine is absorbed quickly after oral administration, reaching a maximum plasma concentration in 6 hours 4.
- It has a half-life of 12 hours and a volume of distribution of 1640 L 4.
- Duloxetine is highly protein bound and is widely distributed throughout tissues 3.
- It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites are mainly excreted in the urine 3.
Efficacy and Safety
- Duloxetine has been shown to be effective in the treatment of generalized anxiety disorder (GAD), major depressive disorder (MDD), neuropathic pain, fibromyalgia, and stress urinary incontinence 3, 4, 7.
- It has a favorable safety profile, with most adverse events being mild to moderate in severity 3, 4, 7.
- Common adverse events include nausea, dry mouth, headache, constipation, dizziness, and fatigue 3, 4.