SNRI Antidepressants: Cymbalta, Effexor XR, Pristiq

Apocalypse Suicide Page
Good Mood
Living with Depression
Mental Health Recovery
NIMH
SHOCKED! ECT

HealthyPlace.com Radio
Depression Support Groups

Books on Depression
Conference Transcripts
Depression Videos
Diaries - Journals
Disorders Definitions
Mental Health News
Online Depression Tests
Psychiatric Medications
Resources
Site Map

Email
ICQ
Instant Messenger

Visit and Post

Abuse
ADD/ADHD
Addictions
Anxiety-Panic
Bipolar
Eating Disorders
Personality Disorders
Self-Injury

send this page to a friend

SNRI Antidepressants
(Serotonin-Norepinephrine Reuptake Inhibitors)

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

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 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.

Side Effects of Cymbalta and Effexor XR

The most common side effects shared by Effexor XR and Cymbalta include:

Nausea
Dizziness
Fatigue or Sleepiness
Insomnia
Dry Mouth
Loss of Appetite
Nervousness
Sweating
Abnormal Vision
Abnormal Ejaculation
Constipation

Before Taking These Drugs

Just as with other antidepressants, you've got to be sure to tell your doctor if you've ever had allergies to any antidepressants, foods, preservatives, or dyes, and if you have suffered from manic depression, convulsions, or seizures. Be sure to report liver disease, since this condition may raise blood levels of any antidepressant, which can increase the risk of side effects. And if you've had a recent heart attack, you may not be able to take antidepressant medication.

In the last few years, some study results and case reports suggested that taking antidepressants was linked with an increase in suicides, attempted suicides, and thinking about suicide—especially for children, teens, and young adults. Generally, the risk is higher in first month or so and then appears to decrease as the body adjusts to the medication. Depressed individuals may be more likely to attempt or commit suicide whether or not they are taking antidepressants. Nevertheless, in 2004, the FDA required the manufacturers of all antidepressants to include on their labels the following safety warning:

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders.

Possible Important Adverse Interactions

As with all antidepressants, you should talk to your doctor before taking any other drugs (even nonprescription medications).

Both Effexor XR and Cymbalta may raise blood pressure in some patients. Your blood pressure should be controlled before starting treatment and should be monitored regularly.

Effexor also tends to increase the heart rate, especially at higher doses. Use Effexor with caution if you've recently had a heart attack, suffer from heart failure, or have an overactive thyroid gland.

Effexor may also cause cholesterol levels to rise in some patients who take it for 3 months or longer. This effect is more common among patients taking higher doses of Effexor.

Mydriasis (prolonged dilation of the pupil of the eye) has been reported with EFFEXOR XR. You should notify your physician if you have a history of glaucoma or increased eye pressure.

You will not be able to use Cymbalta if it causes an allergic reaction. In addition, you should not take Cymbalta if you have uncontrolled narrow-angle glaucoma, a disease that causes increased pressure in the eyes.

Overdose

An overdose of Effexor, combined with other drugs or alcohol, can be fatal. If you suspect an overdose, seek medical attention immediately.

Published retrospective studies report that Effexor overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that Effexor-treated patients have a higher pre-existing burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of Effexor in overdosage as opposed to some characteristic(s) of Effexor-treated patients is not clear. Prescriptions for Effexor XR should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Symptoms of Effexor overdose include:
Sleepiness, vertigo, rapid or slow heartbeat, low blood pressure, seizures, coma.

There is limited clinical experience with Cymbalta overdose in humans. In premarketing clinical trials, cases of acute ingestions up to 1400 mg, alone or in combination with other drugs, were reported with none being fatal. Postmarketing experience includes reports of overdoses, alone or in combination with other drugs, with duloxetine doses of almost 2000 mg. Fatalities have been very rarely reported, primarily with mixed overdoses, but also with duloxetine alone at a dose of approximately 1000 mg.

Signs and symptoms of overdose (mostly with mixed drugs) included:
serotonin syndrome, somnolence, vomiting, and seizures.

Pregnancy and Breast-Feeding

If you want to get pregnant while you're on an antidepressant, you're going to have to weigh the risks to your baby against the risks to you if you don't take the drug. As with most antidepressants, what we know about their activity in pregnant women is mostly obtained from animal studies, not from large-scale studies in humans.

The effects of Effexor XR and Cymbalta during pregnancy have not been adequately studied. If you are pregnant or are planning to become pregnant, tell your doctor immediately. These medications should be used during pregnancy only if clearly needed.

If Effexor or Cymbalta is taken shortly before delivery, the baby may suffer withdrawal symptoms. It's also known that Effexor and Cymbalta appears in breast milk and could cause serious side effects in a nursing infant. You'll need to choose between nursing your baby or continuing your treatment with these SNRIs.

If a woman needs to take an antidepressant during pregnancy, most of the time the doctor will recommend an SSRI like Zoloft or Lexapro.

You and your doctor should weigh the potential risks to the fetus and to you before you decide whether or not to take antidepressants during pregnancy.

There's always a potential for adverse reactions in nursing infants. If you're a new mom, you need to weigh the risks to you of not taking medication against the potential harm to your baby.

Use with the Elderly

If you're over age 60, you're more likely to be sensitive to all of the antidepressants. This means your depression will probably respond to lower doses of medication. It also means you are at higher risk for developing side effects.

Antidepressants such as Effexor and Cymbalta may cause fluid retention, especially if you are an older adult.

advertisement

Some antidepressants may be a better choice than others, of course. For example, studies with Wellbutrin in a limited number of patients over age 60 haven't found any significant problems caused by the drug.

Sources

Anderson IM. Meta-analytical studies on new antidepressants. Br Med Bull. 2001;57:161-178.
Cymbalta [package insert]. Indianapolis, IN: Eli Lilly and Company; May 10, 2007.
Effexor XR [package insert]. Philadelphia, PA: Wyeth-Ayerst; March 2007.
Perahia DG, Pritchett YL, Kajdasz DK, et al. A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res. Epublished ahead of print. April 17, 2007.
Perahia DG, Kajdasz DK, Royer MG, Walker DJ, Raskin J. Duloxetine in the treatment of major depressive disorder: an assessment of the relationship between outcomes and episode characteristics. Int Clin Psychopharmacol. 2006 Sep;21(5):285-295.
Gartlehner G, Hansen RA, Thieda P, et al. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7. (Prepared by RTI International-University of North Carolina Evidence-based Practice Center under Contract No. 290-02-0016.) Rockville, MD: Agency for Healthcare Research and Quality. January 2007. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed January 25, 2007.
A Surgeon General's Perspective: Achieving Remission in Depression, (CME course) Dec. 15, 2004.

SNRI Antidepressants(Serotonin-Norepinephrine Reuptake Inhibitors)