Post-stroke pain may present immediately after a stroke, or develop years later. The prevalence is unclear, but estimated to be anywhere from 2 to 25 percent in the first year after stroke. The underlying mechanisms are not well understood, which in turn limits effective treatment strategies. The results of this systematic review of randomized controlled trials evaluating therapies for central post-stroke pain (CPSP) are inconsistent with the clinical practice guidelines of three major Pain professional groups. While the three groups recommend tricyclic antidepressants and anticonvulsants as first-line therapy, this review found (very low certainty evidence) that anticonvulsants, tricyclic antidepressants, opioid antagonists, and electroacupuncture have no effect on reducing CPSP.
The authors found low certainty evidence that apipuncture (acupuncture using bee venom) may reduce pain, anticonvulsants may improve sleep, repetitive transcranial magnetic stimulation has no effect on depressive symptoms or patient-reported global improvement, and TCAs do not improve depressive symptoms but do produce significantly more side effects. The results for anticonvulsants were based on 4 trials, with a total of 307 patients. The results for TCAs were based on one trial with 15 participants, which is the basis for the recommendation by the three pain professional groups. This trial reported that there was a significant decrease in pain intensity with amitriptyline during the fourth and final week of treatment, but the authors of this systematic review analyzed the data and did not find a significant effect. The results for opioid antagonists, TMS, apipuncture, and electroacupuncture were all based on single trials.
The review was done in a very comprehensive manner, including the breadth of sources evaluated, inclusion of pharmacologic and non-pharmacologic therapies, and the systematic approach for assessing eligibility of studies. They also evaluated many patient-important outcomes (not just improvement of pain), and graded the level of certainty in the evidence using the GRADE approach in which randomized controlled trials begin as “high certainty” and drop down due to risk of bias, inconsistency, indirectness, imprecision, and publication bias.
Eight English-language studies were ultimately included, after an initial review of 5,015 initial entries including 324 full text articles. Studies were eligible if they enrolled at least 10 patients with CPSP, randomly assigned them to a treatment or control arm, and collected outcome data at least 14 days post treatment. If a study enrolled a mixed clinical population, they were included if the results of the CPSP patients were reported separately or at least 80% of the sample were CPSP patients. Risk of bias was assessed for each study based on presence of random sequence generation, allocation concealment, blinding of participants and study personnel, and incomplete outcome data.
To me, the take-home message is really the (poor) level of evidence, rather than the negative results. If very low level evidence suggests a treatment is ineffective, it may just need to be studied in a more thorough and bias-free manner. The authors recommend large, multi-center, randomized trials using standard instruments with established outcome measures, longer observation periods, and reduction of bias. Ideally, these types of studies would be carried out on existing therapies to assess their true utility in the treatment of CPSP while we continue to develop new treatment strategies.