Switching from an SSRI to an SNRI typically involves gradually tapering off the SSRI under a doctor’s guidance and starting the SNRI at a low dose.

Switching from a selective serotonin reuptake inhibitor (SSRI) to a serotonin-norepinephrine reuptake inhibitor (SNRI) is a common step for individuals whose depression isn’t fully managed with their current medication.

While both classes of antidepressants help regulate mood, they work in slightly different ways, and the switch can come with its own set of challenges.

Understanding the differences, potential side effects, and reasons for switching can help you make a smoother transition and achieve better treatment outcomes.

Research suggests that about two-thirds of people with major depression don’t respond to their first antidepressant, often needing a switch after 3 to 4 weeks without improvement at an adequate dose.

If your SSRI isn’t effective, your doctor might suggest trying an SNRI.

SSRIs work by increasing serotonin levels in the brain, which helps improve mood and reduce anxiety. SNRIs, however, increase both serotonin and norepinephrine.

Norepinephrine plays a key role in regulating energy, alertness, and the body’s stress response. This combined effect can provide additional benefits, such as improved energy levels and relief from chronic pain.

Research also suggests that SNRIs may produce faster antidepressant effects, possibly due to their impact on dopamine.

Here are the main reasons people switch from an SSRI to an SNRI:

  • Incomplete symptom relief: If an adequate trial of an SSRI hasn’t relieved your depression or anxiety, an SNRI might help by targeting both serotonin and norepinephrine for a more balanced effect. Some evidence suggests that clinicians prefer SNRIs for individuals with more severe or complex depression, potentially due to their dual action on serotonin and norepinephrine pathways.
  • Coexisting symptoms or conditions: If you also experience chronic pain, fatigue, or low energy, an SNRI might be more effective because it addresses both mood and these additional symptoms.
  • Side effects: If SSRIs cause side effects like sexual dysfunction or weight gain that are difficult to tolerate, an SNRI might give you similar benefits with fewer issues.

Switching between antidepressants requires careful planning and monitoring to reduce risks like withdrawal symptoms and drug interactions.

These are the primary approaches:

  • Conservative approach: This involves slowly reducing the dose of the first antidepressant, followed by a washout period, which is a set time length of time to allow the drug to leave the body. This is usually about five half-lives (or longer for medications like fluoxetine). While the safest method, it takes longer and requires time off medication.
  • Moderate approach: This shortens the washout period to about 2 days, offering a balance between safety and convenience and making it suitable for general practice.
  • Direct switch: (Note that this is only for certain cases and requires expertise.) Stop the SSRI and start the SNRI the next day at a typical therapeutic dose. This method is faster but increases the risk of withdrawal symptoms and drug interactions. It’s generally used under close supervision.
  • Cross-tapering: Gradually decrease the SSRI dose while introducing the SNRI at a low dose. The SNRI is slowly increased as the SSRI is tapered off. This method helps reduce withdrawal symptoms while transitioning to the new medication, but it also requires careful monitoring.

When switching from an SSRI to an SNRI, it’s important to be aware of the risks to ensure a smooth transition and avoid complications like increased anxiety, blood pressure changes, or other adverse effects.

Here are some of the main considerations:

  • SSRI withdrawal: Tapering off an SSRI to switch to an SNRI can lead to withdrawal symptoms like dizziness, nausea, irritability, and flu-like symptoms, especially if the SSRI isn’t tapered slowly. Though some evidence suggests longer use may lead to more severe withdrawal, research on this is limited and inconsistent.
  • SNRI onset: Starting an SNRI too quickly can also lead to side effects such as nausea, dizziness, and headaches. A gradual increase in dose is often necessary to help the body adjust.
  • Serotonin syndrome: Both SSRIs and SNRIs increase serotonin levels. If there’s an overlap during the switch, it could potentially lead to serotonin syndrome, a rare but serious condition involving symptoms like agitation, rapid heart rate, high blood pressure, fever, and confusion.
  • Mood changes: During the switch, some people may experience mood changes, increased anxiety, or worsening depression, though this isn’t guaranteed. These fluctuations can occur as your body adjusts to the new medication.
  • Increased blood pressure: SNRIs, especially venlafaxine, can increase blood pressure, especially at higher doses. This effect may be concerning for individuals with preexisting high blood pressure or those who are at risk.
  • Interactions with other medications: Interactions between SSRIs and SNRIs can affect their effectiveness or increase side effects, particularly when combined with drugs that influence serotonin or blood pressure. Some antidepressants have fewer interactions than others. Desvenlafaxine, an SNRI for major depressive disorder, has a unique, simple metabolic profile, which lowers the risk of drug interactions.

Switching from an SSRI to an SNRI can offer benefits if your current medication isn’t providing the desired results or if you’re experiencing symptoms like chronic pain or low energy.

SNRIs can be more effective for people living with both depression and pain, as they address both serotonin and norepinephrine levels.

Understanding these reasons, along with potential benefits and drug interactions, can help you make an informed choice with your healthcare professional for better treatment outcomes.