Effect of pre-operative pain treatment by means of duloxetine on postoperative outcome after total hip or knee arthroplasty

Total joint replacement (TJR) is considered to be one of the most safe,
successful, and cost-effective treatments for advanced osteoarthritis. However,
it cannot be forgotten that TJR involves major invasive surgery, therefore not
riskless. Residual pain seems to be a major factor of patient*s dissatisfaction
following THA/TKA. Despite the undeniable benefits of TJR, the proportion
patients suffering from residual pain is relatively high. In the past decade it
became clear that experienced osteoarthritis pain is probably not solely
nociceptive. Changes within the central nervous system are presumably
accountable for accessory pain amplification and sensitization. Currently there
are indications that a pre-operative degree of central sensitization is
associated with poorer postoperative outcomes, like residual pain.
It is plausible that pre-operative treating of central sensitization could
enhance the effectiveness of THA/TKA. Duloxetine, an antidepressant, has shown
to be effective in several chronic pain syndromes in which central
sensitization is likely one of the underlying pathophysiological pain
mechanisms. For that it is hypothesized that, pre-operative screening of
centralized pain and treatment with Duloxetine could enhance postoperative
outcome.

Primary:
To determine the degree pain relief 6 months after THA/TKA when screened
pre-operative for centralized pain and subsequent treated accordingly for a
period of 10 weeks with Duloxetine compared to usual care (no Duloxetine)

Secondary:
To determine the effect at different follow-up time points when screened
pre-operative for centralized pain and subsequent treated accordingly for a
period of ten weeks with Duloxetine compared to treated as usual (no
Duloxetine) on:
* The degree of pain relief and neuropathic pain symptoms;
* The degree of sensitisation/sensitivity (measured by QST);
* The degree of functional improvement
and physical activity;
* Quality of life and perceived
satisfaction//expectation level (at the
time on waiting list);
* Depressive and anxiety symptoms.
* The degree of Pain Catastrophizing

Multi-centre, pragmatic, prospective, open-label, randomized clinical trial
(RCT)

The intervention group receives pre-operative Duloxetine for a period of 10
weeks, the control group receives usual care (no Duloxetine)

When compared to routine clinical care the burden and risks associated with
participation are:
1. Group A (duloxetine intervention) subjects have to visit, for safety and
medication usage reasons, the out-patient clinic more frequently than group B
(usual care) subjects and non participants. Therefore this study imposes, for
group A (duloxetine intervention) subjects, at least 4 extra visits, compared
to non participants. For group B (usual care) subjects this study imposes 1
extra visit, compared to non participants. All the other visits will be
combined with standard care, so no additional effort is needed.
2. During the baseline visit (T0) extra blood will be drawn to check for
duloxetine contra-indications/safety. Furthermore, at time point T1, extra
blood will be drawn to check for duloxetine induced hyponatraemia.
3. At 8 time points questionnaire assessment
4. Quantitative sensory testing at 4 time points (T0-T3) for group A subjects
(duloxetine subjects), and at 2 time points (T0+T3) for group B subjects (usual
care).
5. Half of the patients will be exposed to Duloxetine (Group A), thus those
subjects could suffer from related adverse events. The potential benefits for
participating subjects are that Duloxetine could relieve pre- and postoperative
osteoarthritis related pain and improve function.