Drug Comparisons

Depression can occur if some of the neurotransmitters (chemicals that carry messages between nerve cells) in the brain are not functioning effectively. Released by one part of nerve cells, the neurotransmitters float across the synapse (the space between nerve cells) to stick on specific places known as receptors on other cells. Occupying the receptors activates the second nerve cell to release additional neurotransmitters that keep the message going along the nervous system. Once they have delivered their messages, neurotransmitters are either broken down by enzymes or taken back into the nerves in a process known as reuptake.

The three main neurotransmitters involved in depression are dopamine, norepinephrine, and serotonin (also known as 5-HT). In Canada, Europe, and other areas of the world, norepinephrine is known as noradrenaline. 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.

Currently, no strong evidence firmly recommends any individual antidepressant or even any of the antidepressant classes for every situation. Not all patients will respond to the same antidepressant and an individual's response may change over time. Often, a different antidepressant in the same class will be effective, but sometimes a change to a different type of antidepressant is needed. Patients with resistant or recurring depression may need to take two or more antidepressants from different classes at the same time. The choice of an antidepressant depends on multiple factors that include:

• the type of depression being treated
• the doctor's experience
• any other medical conditions the patient may have
• other medications the patient takes
• the patient's response to previous therapy
• the patient's prescription formulary

Drugs in this Class
Venlafaxine Tablets (Effexor Tablets)
Duloxetine Delayed-Release Capsule (Cymbalta Delayed-Release Capsule)

Summarizing the Evidence

Two recent studies found duloxetine and extended-release venlafaxine comparable in effectiveness. In both studies, patients took either 60 mg per day of duloxetine or 150 mg per day of extended-release venlafaxine 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 duloxetine and 225 mg per day for extended-release venlafaxine. Nearly 75% of patients taking extended-release venlafaxine finished 12 weeks of treatment as compared to about 65% of patients taking duloxetine. Duloxetine was associated with more nausea, but a few patients taking extended-release venlafaxine experienced increases in blood pressure.

Duloxetine

• In other studies, duloxetine 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 fluoxetine or paroxetine. An analysis of separate studies done with duloxetine and fluoxetine found little difference in effectiveness between the two drugs.

Venlafaxine

• In one 6-week-long study comparing venlafaxine and trazodone (a miscellaneous antidepressant) for 115 patients, both drugs were about equally effective, but trazodone may have reached full effectiveness faster. A longer (one year) study of trazodone versus venlafaxine also showed that both drugs treated depression about equally. In that study, patients taking trazodone had less insomnia, but venlafaxine was better at relieving problems with thinking and memory. Patients taking venlafaxine reported having more nausea, but trazodone may have caused more dizziness and drowsiness.
• An 8-week study of 115 patients with major depression found that venlafaxine and the tricyclic antidepressant, amitriptyline were about equally effective. Patients taking amitriptyline reported more side effects, however.
• In one study of patients with bipolar disorder, venlafaxine caused more inappropriately excessive happiness than bupropion (a drug in the miscellaneous class of antidepressants). Formerly known as manic-depressive illness, bipolar disorder is a condition that involves drastic mood swings from extreme sadness to exaggerated feelings of happiness.

Venlafaxine Extended Release

• An analysis of over 40 studies that involved about 4,000 patients found that taking extended-release venlafaxine 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 extended-release venlafaxine 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 extended-release venlafaxine stopped taking medication before their studies were scheduled to end.
• A study of 348 adults compared the effects and side effects of extended-release venlafaxine and the miscellaneous antidepressant, extended-release bupropion for 12 weeks. While both antidepressants worked about equally, extended-release venlafaxine may have produced more sexual side effects, which caused more patients in the extended-release venlafaxine group to stop treatment.

Dosing and Administration

Note: Drug treatment for depression is highly individualized. Although many patients respond to recommended dose ranges; some can be treated with lower doses and others need higher doses. In general, treatment starts with a low dose, which is increased at specific intervals only if depression is not relieved. The maximum effectiveness of any antidepressant may take several weeks to develop and more than one antidepressant may be tried before the patient responds to treatment. Once an effective drug and dose are found, the patient is likely to continue therapy for 6 months or longer. When treatment is stopped, the dose of the antidepressant must be decreased slowly over several weeks or months.

• For treating depression, duloxetine is usually taken twice a day in doses totaling 40 mg or 60 mg per day.
• Immediate-release venlafaxine is usually taken with food in two doses or three doses per day. Beginning at 75 mg per day and usually effective at about 150 mg to 225 mg per day, the dose may increase to as high as 375 mg per day for patients with severe depression.
• Most depressed patients begin extended-release venlafaxine at a dose of 75 mg once per day. If blood levels are not adequate, the dose may be raised at intervals of about 4 days to a maximum dose of 225 mg per day.

Generic Availability

• Immediate-release venlafaxine tablets are available in generic formulations. Generic medications may be a less expensive but comparably effective treatment option.
• Duloxetine capsules and extended-release venlafaxine capsules are not available generically at this time.

Drug Interactions

Some interactions between medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how the drugs interact and the severity of the interaction, please use our Drug Interactions Checker.

Side Effects

To view specific side effect information, please use our Side Effect Checker.

Additional Information

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.

• Duloxetine and extended-release venlafaxine are both FDA-approved for treating 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.
• Extended-release venlafaxine is also approved for treating panic disorder and social anxiety disorder.
• Sexual dysfunction includes the loss of interest in having sex, the failure to complete sexual relations or the inability to feel pleasure from having sex. Interference with normal sexual functioning is often associated with depression and it appears to increase as depression becomes more severe. Many antidepressants interfere with sexual performance, as well. Results from one study indicate that sexual performance generally got worse for patients taking extended-release venlafaxine while patients taking a miscellaneous antidepressant, bupropion extended release, reported overall improvements in sexual function.

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Last Updated: July 2007
This content was created by members of the DrugDigest team of experts and is solely under DrugDigest's editorial control.

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