Fifteen studies (n=6,142 patients) were included in the review: eight placebo-controlled double-blind clinical trials; five active-controlled double-blind clinical trials; and two long-term open-label trials with no comparator group.
The most common adverse events were gastrointestinal (nausea, constipation and vomiting) and central nervous system-related events (dizziness, somnolence and headache). Patients who received tramadol reported adverse event rates of 45% to 84% compared to 19% to 66% in patients who received a control; 80% to 90% of reported events were described as mild to moderate severity. One open-label study reported rates between 88% and 91% in patients who received tramadol. Three fixed-dose and two flexible-dose studies showed contrasting findings for tramadol dose and rates of gastrointestinal and central nervous system-related events. Discontinuation rates ranged between 10.2% and 76%, of which between 1.7% and 53.7% were due to adverse events.
Incidence rates for different tramadol formulations overlapped for the most common gastrointestinal and central nervous system-related events. However, incidence of dizziness was higher for the long-acting formulations compared with tramadol immediate release and rates of gastrointestinal events were lower for some long-acting formulations compared to immediate release formulations (incidence rates were reported in the review). Three studies reported that incidence of adverse events was highest during initial treatment and declined with continued treatment. Similarly, five studies reported that discontinuation rates due to adverse events were highest during initial treatment compared to continued treatment.
Findings on treatment dose and adverse events were reported in the review.