Abstract
Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain. Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis. Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects. Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients' comorbidities and co-medication.
Highlights
Chronic pain is a prevalent condition which affects 36% of the population in US (19% in Europe, respectively) and reduces quality of life
Traditional agents, such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), are efficacious in the treatment of chronic pain but they are limited by adverse effects, tolerance, and potential for addiction
Not intended to treat chronic pain, various antidepressants were shown in large randomized-controlled trials (RCT) to be efficacious in the treatment of chronic pain conditions, such as diabetic neuropathy or migraine [1]
Summary
Chronic pain is a prevalent condition which affects 36% of the population in US (19% in Europe, respectively) and reduces quality of life. While multimodal treatment regimens including both pharmacological and non-pharmacological interventions are most effective in the treatment of chronic pain, pain medication is still the second most prescribed group of drugs in the US alone, accounting for 12% of all prescriptions [2] Traditional agents, such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs), are efficacious in the treatment of chronic pain but they are limited by adverse effects, tolerance, and potential for addiction. Not intended to treat chronic pain, various antidepressants were shown in large randomized-controlled trials (RCT) to be efficacious in the treatment of chronic pain conditions, such as diabetic neuropathy or migraine [1]. There is inconsistent data on adverse effects and tolerability of antidepressants in the treatment of chronic pain. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain
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