Monday, November 9, 2015

Duloxetine (Cymbalta)

Duloxetine (Cymbalta) is another newer antidepressant, approved in the US in 2004, and in Canada in 2007.  It is a reuptake inhibitor of both serotonin and norepinephrine, and is most similar in this regard to venlafaxine (Effexor).  

In a study of medication treatment options for severe depression, a switch to duloxetine was compared with a dose increase of escitalopram.  The escitalopram group had better results, including a remission rate of 54% for escitalopram vs. 42% for duloxetine.  ( )

Another similar comparative study also favoured escitalopram 10-20 mg daily over duloxetine 60 mg, both in terms of effectiveness and side effect profile.  In this study 2% of the escitalopram group dropped out due to side effects, compared to 13% of the duloxetine group.
( )

In this well-done 2011 review by Schueler et al. comparing venlafaxine and duloxetine with SSRIs.  They concluded the following:
1) Venlafaxine had superior efficacy in response rates but inferior tolerability to SSRIs
2)  Duloxetine did not show any advantages over other antidepressants and was less well tolerated than SSRIs and venlafaxine.
( )

Another study, done in 2006, also showing evidence that venlafaxine is superior to duloxetine:

In one of the few well-designed comparative studies of venlafaxine vs. duloxetine, done by Perahia et al (2008), the two medications are found to have similar effectiveness, but with a higher dropout rate due to side effects in the duloxetine group. ( )   A look at graphs of symptom change show that the two medications appear identically effective.  But duloxetine caused more side effects, especially nausea.  It is true that discontinuing venlafaxine causes more side effects than discontinuing duloxetine, but this could be framed as a technical matter that just needs to be managed by very slow tapering.

This 2012 study (sponsored by the manufacturer!) by Martinez et al ( ) compares duloxetine with SSRI treatments for major depression, in a 12 week prospective trial.  Duloxetine performed well, but on the primary outcome measure there was no significant difference in response or remission rates.  On secondary measures there appeared to be some advantages for duloxetine, particularly for pain symptoms.  But the study was not intended to be for treating pain syndromes!  SSRIs are known to be ineffective for pain!
 Duloxetine is often touted as a good treatment for neuropathic pain.  And numerous studies do show that it can help.  But how does it actually compare to other options?  Specifically, how does it compare with a much cheaper and similar antidepressant, venlafaxine?   Rudroju et al (2013) looked at comparative effectiveness of various medications for treating neuropathic pain.  Many medications helped, including duloxetine.  But in this study, gabapentin and venlafaxine had the best odds ratio of helping, followed by pregabalin. Duloxetine was farther down the list.  With a benefit-risk analysis, which takes into account side effects and tolerability, gabapentin, pregabalin, and venlafaxine were once again at the top of the list of best agents, with duloxetine farther down.

Duloxetine (Cymbalta) costs about $4.23 for a 60 mg dose, compared to $0.38 for an equivalent 150 mg dose of Effexor XR.  So it is about 10 times more expensive than an alternative which is shown to work as well if not better. 

In conclusion, Cymbalta is yet another newer antidepressant which is not necessarily better than alternatives; in fact the alternatives such as Effexor XR are probably equally effective or more effective.   It is marketed intensely as a treatment for neuropathic and other pain syndromes, but alternatives such as Effexor XR work better, with fewer side effects, at a lower cost.   Therefore, just as with the other antidepressants mentioned in the previous posts, Cymbalta could be considered a third-line option, which might suit some people well if they have tried other things unsuccessfully.

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