Antidepressants can play a key role in alleviating painful conditions
like osteoarthritis and may result in fewer side effects than
traditionally prescribed drug regimes, such as anti-inflammatories and
opioids, according to a perspective paper published online ahead of
print publication by the International Journal of Clinical Practice.
American doctors Leslie Citrome and Amy Weiss-Citrome analysed the
latest clinical evidence on duloxetine, a well-established
antidepressant that received US Food and Drug Administration (FDA)
approval in 2010 for use with chronic musculoskeletal pain, including
osteoarthritis.
“It is not uncommon to treat osteoarthritis with a combination of drugs
that work in different ways” explains Dr Leslie Citrome, Clinical
Professor of Psychiatry and Behavioural Sciences at New York Medical
College, Valhalla, New York, USA. “Our review supports this approach and
confirms that antidepressants are not just for depression and can play a
key role in relieving this painful condition.”
The authors looked at studies exploring the effects of duloxetine being
used on its own or in combination with non-steroidal anti-inflammatory
drugs (NSAIDs). These included the two randomised double-blind, placebo
controlled clinical trials that formed the basis of FDA approval for
duloxetine for the treatment of chronic pain associated with
osteoarthritis.
Study results were analysed using number needed to treat (NNT) and
number needed to harm (NNH). These quantify how many patients need to be
treated with one intervention versus another before encountering one
additional patient who experiences a desired outcome (NNT) or undesired
disadvantage, such as a side-effect (NNH). A smaller number indicates
greater advantages for NNT and greater disadvantages for NNH.
“Applying these simple methods to often complex research gives us a real
indication of whether a drug will benefit or harm our patients, which is
what we as clinicians are most interested in” explains Dr Citrome.
When duloxetine was compared with a placebo tablet containing no active
ingredients, using data from the two FDA approval studies, the NNT was
six. This means that six patients would need to be treated with
duloxetine instead of receiving the placebo before encountering one
additional patient experiencing an improvement in pain using a composite
measure that brings together a number of indicators of efficacy. Such a
low NNT makes a compelling case for this treatment approach.
The authors say that this finding, over 13 weeks, compared favourably
with other studies of NSAIDs - the NNT was five for etodolac after four
weeks and four for tenoxicam after eight weeks.
When the side effects of the various drugs were taken into account, this
showed that when duloxetine was used on its own for 13 weeks it provided
a number of advantages over NSAIDs, which can lead to gastrointestinal
bleeding, and opiates such as morphine, which can cause constipation.
The most common side effects of duloxetine - nausea, fatigue and
constipation - were small when compared to the placebo, resulting in
NNHs of 16, 17 and 19 respectively. This means, for example, that 16
patients would need to be treated with duloxetine instead of receiving
the placebo before encountering one additional patient experiencing
nausea.
The studies used to gain FDA approval also showed that pain reduction
using duloxetine on its own was not dependent on an improvement in
depressive symptoms.
“Although the use of duloxetine as a monotherapy for pain has been
approved by the regulatory agencies, it is quite common for patients to
receive a combination of drugs and NSAIDs are the most frequently
prescribed drugs for the pain associated with osteoarthritis” says
co-author Dr Amy Weiss-Citrome, a specialist in Physical Medicine and
Rehabilitation.
For that reason the authors also examined the findings of a recent study
that showed the potential synergy of duloxetine and NSAIDs.
The study, a ten-week double-blind trial of 524 patients with
osteoarthritis of the knee, found that those who took a combination of
duloxetine and NSAIDs reported greater pain reductions than the control
group who took a NSAID with a placebo.
The NNT for the outcome of substantial improvement in pain with
combination treatment versus NSAIDs alone was six, underlining the
benefits of this approach.
“We believe that our analysis of these studies demonstrate that
clinicians managing patients suffering from osteoarthritis should also
consider prescribing adjunctive antidepressants that can effectively
impact on central pain pathways” concludes Dr Leslie Citrome.
The paper is free online at: http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2012.02899.x/pdf
