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Antidepressants Comparison: Effexor versus Cymbalta
SNRIs - new class of antidepressants
Serotonin norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used to treat depression and other affective disorders. SNRIs were developed more recently than SSRIs and currently there are only two medications in this class approved by the FDA for use: venlafaxine (brand name: Effexor) and duloxetine (brand name Cymbalta). These new drugs, because of their specificity for the serotonin and norepinephrine reuptake proteins, lack most of the adverse side effects of tricyclic antidepressants and monoamine oxidase inhibitors. Venlafaxine HCl is the first and most commonly used SNRI. Venlafaxine was first introduced by Wyeth Pharmaceuticals in 1993, and marketed under the trade name Effexor. Duloxetine HCl, manufactured by Eli Lilly, is the newest antidepressant on the market. It was approved by the FDA and released on the market in August 2004. SNRIs have the ability to affect two neurotransmitters - serotonin and norepinephrine. Clinical studies have shown that the SNRIs are generally quicker acting and more effective in treating severe major depressive disorder, treatment-resistant depression, and depressive symptom remission than SSRI antidepressants, and tricyclic antidepressants. Comparative studies with SNRIs antidepressants are limited. Currently there is not enough information to firmly recommend any one of these antidepressants over another and selection of antidepressant therapy should be done on an individual basis. Drugs may work differently for different people. What is effective for some may not be effective for others. This article provide some comparative data based on the analysis of medication prescribing information and studies. Mechanism of action
When serotonin and noradrenaline are released from nerve cells in the brain they act to lighten mood. When they are reabsorbed into the nerve cells, they no longer have an effect on mood. It is thought that when depression occurs, there may be a decreased amount of serotonin and noradrenaline released from nerve cells in the brain. SNRI antidepressants work by preventing serotonin and noradrenaline from being reabsorbed back into the nerve cells in the brain. This helps prolong the "mood lightening" effect of any released serotonin and noradrenaline. In this way SNRIs help relieve depression. It may take between two to four weeks for the benefits of these medicines. Effexor XR has the flexibility of being an SSRI at lower doses and an SNRI at higher doses. Cymbalta differs from Effexor in that it is comparatively more noradrenergic. Cymbalta is also used to treat nerve pain in the feet, legs or hands that is due to nerve damage caused by poorly controlled diabetes. Cymbalta is thought to enhance the nerve signals within the central nervous sytem that naturally inhibit pain. Absorption
Food does not affect the bioavailability of Effexor or its active metabolite, ODV (O-desmethylvenlafaxine). Time of administration (AM vs PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule. Food does not affect the maximal plasma concentrations of Cymbalta, but delays the time to reach peak concentration by approximately 4 hours (from 6 to 10 hours) and it marginally decreases the extent of absorption by about 10%. There is a 3-hour delay in absorption and a one-third increase in apparent clearance of duloxetine after an evening dose as compared to a morning dose. The bioavailability of Cymbalta appears to be reduced by about one-third in smokers. However, dosage modifications are not considered necessary. The bioavailability of Effexor is not affected by smoking. Indications and uses
Effexor XR is indicated for the treatment of:
Cymbalta is indicated for the treatment of:
The extended-release formulation of Effexor has been approved for the treatment of generalized anxiety disorder and social anxiety disorder; however, these are not labeled indications for Cymbalta. Shortly after duloxetine was approved for the treatment of depression, FDA approved its use for the management of neuropathic pain associated with diabetic peripheral neuropathy. It is the first drug to be approved for this indication, although tricyclic antidepressants (e.g., amitriptyline) and gabapentin have been used off-label for this problem. Duloxetine is also being evaluated in the treatment of stress urinary incontinence (officially approved in Europe for this problem), generalized anxiety disorder, and fibromyalgia, but these are not labeled indications at the present time. Off-label (investigational) uses
Many doctors are starting to prescribe Effexor "off-label" for the treatment of diabetic neuropathy (in a similar manner to Cymbalta) and migraine prophylaxis (in some people, however, Effexor can exacerbate or cause migraines). Studies have shown Effexor effectiveness for these conditions. It has also been found to reduce the severity of 'hot-flashes' in menopausal women. Effexor is also prescribed for off-label uses such as chronic fatigue syndrome, and obsessive-compulsive disorder (OCD). At present, Cymbalta is not approved for treating bipolar depression, but is being prescribed to people with bipolar disorder as an off-label use. Patients who have experienced mania should be monitored carefully when taking this medication. There are more controlled studies with Cymbalta showing benefit for all kinds of pain than any other antidepressant. In clinical trials, Cymbalta 60 mg once daily demonstrated efficacy in painful physical symptoms associated with depression. Cymbalta is being studied for the treatment of stress urinary incontinence, which may also respond to treatment with both serotonin and norepinephrine. Cymbalta is also showing promise for the treatment of fibromyalgia symptoms. In randomized, controlled, 12-week trial, duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures. Adverse reactions and side effects
The most common side effects associated with Effexor treatment are:
The most common side effects associated with Cymbalta treatment are:
Cymbalta's dual action takes hold at lower doses than does Effexor. As such, the dose related cardiovascular risks that are associated with both drugs might be more avoidable with Cymbalta. Cymbalta is unique among the SNRIs and SSRIs with respect to the extent to which it may increase serum transaminase concentrations and the corresponding risk of hepatotoxicity. Accordingly, it should not be used in patients with any hepatic insufficiency. Because of an increased risk of hepatic effects, Cymbalta should generally not be prescribed for patients who consume substantial quantities of alcoholic beverages. Both Cymbalta and Effexor have caused increases in blood pressure in some patients. Although the two drugs have not been directly compared, data from the studies with the individual agents suggest that blood pressure elevations are more pronounced with Effexor. Cymbalta and Effexor have caused mydriasis in some patients, and patients with increased intraocular pressure or those at risk of acute narrow-angle glaucoma should be monitored. The use of Cymbalta is contraindicated in patients with uncontrolled narrow-angle glaucoma. The use of Effexor has been infrequently associated with the occurrence of seizures, activation of mania, abnormal bleeding, and hyponatremia. Although these events were not identified as problems in clinical trials with Cymbalta, the similarity of its actions warrants caution with respect to these risks. The most common events leading to discontinuation of Effexor XR are: nausea, dizziness, somnolence, insomnia, dry mouth. The most common events leading to discontinuation of Cymbalta are: nausea, dizziness, somnolence. Brief comparison table
References
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