Dresden, Germany—Low doses of antidepressants are often prescribed to relieve chronic pain in conditions such as diabetic neuropathy, migraine and tension headaches, osteoarthritis, and fibromyalgia

An article in Frontiers in Neuroscience notes, however, that some chronic-pain patients struggle with the drugs’ side effects, especially if they are already using other medications or have comorbid health conditions.

To determine what factors most influence tolerability of antidepressant treatment, researchers from University Hospital Carl Gustave Carus in Dresden, Germany, conducted a systematic study and meta-analysis of the reported adverse effects for a wide variety of commonly used antidepressant drugs, each with its own side effect profile.

“Understanding adverse effects and their impact on patients’ quality of life is crucial in modern clinical medicine and poses a substantial challenge to clinicians who face an exponentially growing range of available medical therapies” explained principal investigator Timo Siepmann, MD.

The review divided antidepressants into different categories based on their mechanism of action, such as tricyclic antidepressants amitriptyline and nortriptiline, and serotonin reuptake inhibitors venlafaxine, duloxetine, and milnacipran, among others. All adverse effects reported in the clinical literature over the past 2 decades were compiled, including dizziness, dry mouth, drowsiness, palpitations, weight gain, sexual and urinary dysfunction, hypertension, and more.

Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in the review, and 23 studies were included in the meta-analyses.

The study found that a higher risk for adverse effects compared with placebo was observed in all antidepressants included in the analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation, with amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showing the highest placebo effect-adjusted risk of adverse effects.

Study authors note that the risk for withdrawal due to adverse effects was highest with desipramine (risk ratio: 4.09), followed by milnacipran, venlafaxine, and duloxetine.

“However, overall tolerability was high,” the researchers point out. “Each antidepressant showed distinct risk profiles of adverse effects.”

The study urges prescribers to personalize prescriptions so that, for example, drugs with dizziness and drowsiness as side effects are avoided for those who drive vehicles or operate heavy machinery; however, such drugs might be desirable in a chronic pain patient with sleep disruptions or insomnia.

“Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles,” the researchers conclude. “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.”

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