SNRIs are a newer class of antidepressants for depression. Discover how an SNRI like Cymbalta and Effexor XR work, along with their common side-effects.

The three main neurotransmitters involved in depression are dopamine, norepinephrine, and serotonin (also known as 5-HT). When brain levels of one or more neurotransmitter are low or unbalanced, depression and other conditions can result. Generally, antidepressant drugs work by increasing the production or decreasing the breakdown of one or more neurotransmitter.

One of the newest classes of antidepressants, the selective serotonin and norepinephrine reuptake inhibitors (SNRIs) affect both norepinephrine and serotonin. While low levels of both neurotransmitters are associated with depression, norepinephrine is thought to be involved more with alertness and energy, while serotonin influences mood. By increasing levels of both, SNRIs work on different aspects of depression.

Depression drugs included in this class of antidepressants are: Cymbalta (duloxetine), Effexor XR (venlafaxine) and Pristiq (desvenlafaxine), Wyeth's followup drug to Effexor.

Are there differences among the SSRIs and SNRIs in achieving remission in patients with major depression?

Remission of depression in the patient is the doctor's main goal. According to Dr. Jeffrey Kelsey, Medical Director, Georgia Institute of Mood and Anxiety Disorders, all of the antidepressants that are available in the U.S. market today are equally effective when it comes to response rates. "However, when it comes to remission, the data shows that SNRIs, dual-acting antidepressants, will, in some patients, confer an advantage. And the tricky part is going into it, we don't know which patients will benefit from one approach to the other."

Kelsey says "SSRIs are very effective treatments but some patients are going to get more benefit from a dual-acting antidepressant."

Indications for Using SNRI Antidepressants

Cymbalta, Effexor XR and Pristiq are all FDA-approved for treating major depressive disorder (MDD). Cymbalta and Effexor Xr are approved for treatment of generalized anxiety disorder (GAD), a condition that often accompanies depression.

Duloxetine has an additional indication for relieving diabetic peripheral neuropathic pain, which is caused by nerve damage from diabetes.

Effexor XR is also approved for treating panic disorder and social anxiety disorder.

Which SNRI Antidepressant is Best?

Two recent studies found Cymbalta (duloxetine) and Effexor XR (extended-release venlafaxine) comparable in effectiveness. In both studies, patients took either 60 mg per day of Cymbalta or 150 mg per day of Effexor XR for 6 weeks. For 6 more weeks, patients continued on whichever drug they had started, with doses adjusted to as high as 120 mg per day for Cymbalta and 225 mg per day for Effexor XR. Nearly 75% of patients taking Effexor XR finished 12 weeks of treatment as compared to about 65% of patients taking Cymbalta. Cymbalta was associated with more nausea, but a few patients taking Effexor XR experienced increases in blood pressure.

In other studies, Cymbalta produced general responses that were better than placebo (inactive sugar pills) and similar to those seen with drugs from another class of antidepressants known as selected serotonin reuptake inhibitors (SSRIs)—most commonly Prozac (fluoxetine) or Paxil (paroxetine). An analysis of separate studies done with Cymbalta and Prozac found little difference in effectiveness between the two drugs.

As for Effexor XR, an analysis of over 40 studies that involved about 4,000 patients found that taking this medication was associated with a higher success rate than other types of antidepressants. Success was defined as an improvement of 50% or more in the rating scales used to measure depression. In the analysis, 73.7% of patients taking Effexor XR were considered to be successful, as compared with 61.1% of those taking a selected serotonin reuptake inhibitor (SSRI) and 57.9% taking a tricyclic antidepressant (TCA). In addition, fewer patients taking Effexor XR stopped taking medication before their studies were scheduled to end.

Another study of 348 adults compared the effects and side effects of Effexor XR and the miscellaneous antidepressant, extended-release bupropion (Wellbutrin XL) for 12 weeks. While both antidepressants worked about equally, Effexor XR may have produced more sexual side effects, which caused more patients in the Effexor XR group to stop treatment.

Drugmaker, Wyeth says Pristiq also may be a treatment option for patients who are on multiple medications. The compound has a low risk of drug-drug interactions. This is important when considering that depression often is a co-morbid condition in medically ill patients and that these patients frequently are taking multiple medications.