The use of Cymbalta or Effexor carries a risk of serotonin syndrome , which occurs when there is an excess of serotonin in the brain. Symptoms of serotonin syndrome may include fast heart rate, increased blood pressure, sweating, tremors, and fever.
Cymbalta and Effexor can cause an increase in blood pressure. Those with a history of high blood pressure should be monitored while on treatment with Cymbalta or Effexor. Cymbalta and Effexor should be used with caution in those with a history of bipolar disorder or seizures. These antidepressants may activate mania, hypomania, or seizures in some people. Consult a healthcare provider for other possible warnings and precautions with Cymbalta and Effexor.
Cymbalta is the brand name of duloxetine. It is used for the treatment of major depression and anxiety disorders. It is also used to treat pain from diabetic neuropathy and fibromyalgia. Cymbalta is available in extended-release capsules in strengths of 20 mg, 30 mg, or 60 mg. Effexor is the brand name of venlafaxine. It is used for the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder.
Regular Effexor has been discontinued; however, Effexor XR tablets are available in strengths of But they are not the same drug. In addition to treating major depression and anxiety, Cymbalta is also FDA approved to treat certain types of nerve pain.
On the other hand, Effexor is FDA approved to treat panic attacks and social anxiety. The better antidepressant depends on the condition being treated and other medications a person may be taking. Venlafaxine may be a more effective short-term treatment option for depression. However, it may have a lower tolerability than Cymbalta in terms of side effects, such as sexual dysfunction.
No conclusive studies have shown that Cymbalta or Effexor may be safe during pregnancy. An antidepressant should only be used during pregnancy if the benefits outweigh the potential risks. In some cases, Cymbalta or Effexor may need to be used to control symptoms of depression during pregnancy. Consult a healthcare provider for medical advice before using Cymbalta or Effexor while pregnant.
Alcohol in moderation is likely safe while taking Cymbalta or Effexor. However, drinking alcohol while starting treatment with Cymbalta or Effexor may lead to increased dizziness or drowsiness. It may be advised to discontinue drinking alcohol until it has been a few days after starting treatment. There is no evidence that Effexor directly affects memory. Effexor XR has been known to cause hyponatremia, or low sodium levels in the blood, especially if diuretics are also being taken.
Signs and symptoms of hyponatremia include headache, confusion, and memory impairment. Your doctor may recommend stopping Effexor XR until the hyponatremia resolves. Cymbalta is a selective serotonin and norepinephrine reuptake inhibitor SNRI. Talk to a healthcare provider about potential antidepressant treatment options for you.
The dose of Effexor should be slowly tapered to help prevent serious withdrawal symptoms. A sensitivity analysis for the logistic analysis was conducted to examine for the impact of continuous coding of the prior antidepressant, prior pain medication, and prior medical cormorbidity categories. Utilizing continuous versions of the variables did not change the inference whether they are statistically significant or not for these factors.
Model reliability checking supported the results of the regression analysis. The distribution of health care costs in the 6 months before and 6 months after the index date is presented in Figure 2.
Pre- and post- 6-month average cost for treatment with duloxetine versus venlafaxine XR Wilcoxon signed-rank test for pre and post comparison. This study examined existing clinical practice patterns of SNRIs duloxetine and venlafaxine XR to determine if, in usual clinical practice, they appear to be used as interchangeable medications or if there is evidence of targeted use of each for more specific MDD patient populations.
Patients with MDD who were initially treated with duloxetine tended to be older and to have more complex clinical presentations compared with their counterparts treated with venlafaxine XR. During the year before initiating SNRI treatment, future duloxetine patients were more likely than future venlafaxine XR patients to have a history of comorbid psychiatric and nonpsychiatric conditions, including pain.
As would be expected with a greater comorbid disease burden, patients commencing therapy with duloxetine were also more likely to have had higher previous health care resource utilization and total health care costs compared with the venlafaxine XR cohort. Use of either medication was associated with a net reduction in total medical costs in the 6 months after their initiation, despite higher pharmacy costs.
These findings of substantial differences in pretreatment case mixes and costs between patients initiating treatment with either of the two SNRIs in actual practice patterns appear to be at odds with what might be expected based on their efficacy with each other and with the SSRIs, as reported in clinical trials and comparative effectiveness meta-analyses [ 13 , 14 ].
We suspect that a reason for this apparent discrepancy of trial data from real-world use is the emerging clinical practice pattern of successive step therapy [ 22 , 23 ], as most prominently illustrated in the Sequenced Treatment Alternatives to Relieve Depression STAR-D effectiveness trial [ 9 ]. The STAR-D studies mimic real-world care by initiating treatment with SSRI in all patients, then offering nonremitting patients recommended second-step and third-step treatments.
In STAR-D [ 2 ], nonremitting patients requiring additional treatment steps were predicted by many of the same pretreatment characteristics reported herein: prior treatment nonresponse, multiple comorbid medical conditions, multiple psychiatric comorbidities, as well as more severe depressive symptoms data not available in this study.
Thus, in contrast to clinical trials, which randomize average patients to different treatments, SNRIs are more often initially prescribed to patients with a more complex and challenging clinical picture in usual clinical care.
Use of the SNRIs for complex patients is in line with emerging studies suggesting that SNRIs may be particularly effective in patients with a more severe and complicated initial clinical presentation who are most prone to fail first-line SSRI treatment [ 6 — 8 ]. To best of the authors' knowledge, this is the first study to assess the association of demographics, prior comorbidities, medication use, and treatment cost, with treatment initiation for duloxetine and venlafaxine XR in the usual care of patients with MDD.
The findings demonstrated that duloxetine is primarily used for patients with a complicated disease and medication profile. As with most other retrospective administrative claims data analyses, this study is subject to potential limitations, including selection biases and unmeasured confounding factors.
We examined individuals who were commercially insured and had 12 months of continuous enrollment; patients who did not meet these inclusion criteria were excluded. We also selected the most recent initiation of SNRIs in patients with MDD diagnoses, and this method diverges from the usual practice of starting with an incident diagnosis and having the first medication define an index case in claims studies. Data on MDD severity, treatment outcomes, patient preferences, and health plan restrictions were also unavailable; hence, comorbidities and health care resource utilization serve as indirect indicators of disease severity and outcome.
Although our logistic regression models adjusted for certain confounding factors, potential biases may still exist because of these and other unmeasured factors. The potential confounding impacts of local step-therapy guidelines, and personal insurance drug tiers could also not be examined with available data. The timeframe for the data in this analysis started one year after duloxetine was on the market in order to eliminate 'early adopters' of a new medication and better capture a representative pattern in usual care settings.
However, it is unclear if some of the differences observed here were due to the fact that duloxetine was still the newer antidepressant at this time and whether the observed factors would persist if later data was utilized. Greater clinical severity and low initial dosing have been found to be factors predicting earlier antidepressant switching [ 24 ] and such patients may have preferentially tried the newer medication. We did not assess initial dose in this work and additional confirmatory work utilizing more recent data is warranted.
Finally, the descriptive cost changes over time may reflect regression to the mean that could be common to any added treatment rather than cost-offsets unique to SNRIs. In the light of these potential limitations, the results of this study need to be further replicated and extended using different types of studies in broader patient and medication populations and with direct clinical data to aid in examining the impacts of depression severity and outcomes [ 19 , 25 ].
Duloxetine appears to be prescribed for somewhat more complicated and costly patients than venlafaxine XR. These treatment patterns suggest that both medications have a place on formularies to allow for optimal patient matching, especially for patients not responding to initial step therapy choices.
While clinical guidelines [ 11 ] tend to focus on first-line recommendations, less is known about optimal choices and targeting of patients needing treatment changes after initial nonremission. There is also little evidence-based guidance supporting optimal initial matching to minimize nonremission and the risk that patients will either discontinue treatment or refuse an alternative regimen when first-line care fails.
Patients with MDD receiving initial treatment with duloxetine were more likely to be older and to have comorbid medical conditions and complex prior medication treatment histories compared with their counterparts initially receiving venlafaxine XR. Further research in more heterogeneous patient populations may delineate more definitively the potential patient-related outcomes and treatment cost consequences associated with more optimally targeted SNRI treatments.
List of 17 medical categories; Table 4 used for patients' unique medical conditions. CNS Spectr. Article PubMed Google Scholar. Am J Psychiatry. Biol Psychiatry. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I: Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry. J Clin Psychopharmacol. Depress Anxiety. Ann Intern Med. A meta-analysis of studies of newer agents. J Clin Psychiatry.
Wong DT, Bymaster FP: Dual serotonin and noradrenaline uptake inhibitor class of anti-depressants: potential for greater efficacy or just hype?. Prog Drug Res. Cymbalta duloxetine HCl delayed-release capsules for oral use. US full prescribing information. Eur Psychiatry. Besides treating epilepsy, most of these medications are often used in managing pain such as neuropathic pain and fibromyalgia [ 19 — 21 ].
This may explain the higher odds of initiating duloxetine among patients with pre-period use of anticonvulsants. Venlafaxine XR has additional approved indications in the UK including generalized anxiety disorder, social anxiety disorder, and panic disorder. Duloxetine is now indicated for generalized anxiety disorder, but the indication was not approved until August , which was at the close of our study period.
This may explain, in part, our findings that patients with anxiety disorders had a higher likelihood of initiating treatment with venlafaxine XR than duloxetine. Given that clinical trials show noninferiority in terms of clinical efficacy and tolerability between duloxetine and venlafaxine XR in the treatment of patients with generalized anxiety disorders [ 22 ], we may see an increasing use of duloxetine to treat patients with MDD and generalized anxiety disorders in the future.
Finally, our study found that patients who were on antihyperlipidemics were more likely to initiate duloxetine than venlafaxine XR. Similarly, the Shi et al. Interpreting the results from this study is subject to several challenges inherent to conducting outcome research studies with the GPRD. As in any administrative data source, we assumed the accuracy of codes entered into the database by providers.
Any such omissions or errors could impact the accuracy of the results presented, but the impact across cohorts should be consistent. As mentioned in Section 2 , chronic conditions may not be coded as frequently as they are seen. As a remedy, we extended the pre-period for the evaluation of chronic conditions, thereby increasing the likelihood of their capture. We also identified relevant medication use, which is sometimes a better indicator of comorbidity than diagnoses alone.
For example, the rate of diabetes in the duloxetine cohort was 6. While these limitations may have hindered us from accurately reporting the rates of comorbid conditions, the impact on both treatment cohorts is expected to be equal. Pharmaceutical treatment in this study was evaluated solely on prescription orders recorded by general practitioners.
Patients may not fill the prescriptions or take the medications as prescribed, a factor that cannot be assessed in the GPRD. Thus, evaluations of prescription medication use reflect how the medications were prescribed, but not necessarily how patients actually took the medications. Prescriptions provided in a hospital or secondary care setting including non-GP practitioners, as well as over-the-counter medications were not captured.
But it does not include the homeless, the incarcerated, members of the armed forces, or individuals who obtain care in private practices. Thus, our study results are not generalizable to the entire UK population. Based on a total of 2, patients who newly initiated duloxetine or venlafaxine XR, our study suggested that older age, preexisting unexplained pain, anxiety disorders, and respiratory disease, as well as pre-period use of opioid analgesics, antihyperlipidemics, and anticonvulsants were significant predictors of the initiation of duloxetine versus venlafaxine XR.
In the UK primary care system, treatment choice of duloxetine or venlafaxine XR appears to be driven by patient-specific mental and medical health characteristics with general practitioners favoring duloxetine over venlafaxine XR when pain conditions coexist with depression. Shi, E. Durden, and Z. Cao are employees of Thomson Reuters and provided consulting services to Eli Lilly. Torres was an employee of Thomson Reuters and provided consulting services to Eli Lilly.
This study was fully funded by Eli Lilly and Company. Happich receives salary and holds stocks from Eli Lilly that commercializes duloxetine and has financed this publication. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Academic Editor: Charles B. Received 05 Jan Revised 14 Mar Accepted 01 Apr Published 07 Jun Abstract Background. Introduction Major depressive disorder MDD is a mood disorder characterized by persistent feelings of sadness, a pervasive low mood, diminished ability to experience pleasure, and cognitive symptoms such as difficulty concentrating and impaired memory.
Materials and Methods 2. Figure 1. Table 1. Demographic characteristics of patients Initiating duloxetine or venlafaxine XR. Table 2. Pre-period clinical characteristics of patients initiating duloxetine or venlafaxine XR. Table 3. Pre-period medication use 1 among patients initiating duloxetine or venlafaxine XR. Figure 2. Logistic regression predicting duloxetine or venlafaxine XR at index.
Venlafaxine XR served as the reference group in the model. Only predictors with statistical significance are displayed. References N. Singleton, R. Bumpstead, M. McCrone, S. Dhanasiri, A. Patel et al. Papakostas, M. Thase, M. Fava, J. Nelson, and R. Thase, Y. Pritchett, M. Ossanna, R. Swindle, J. Xu, and M. Kienke and J. Shelton, A.
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