Abstract
BackgroundAntidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants’ classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants’ classes with movement disorders.MethodsUsing VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders’ reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders.ResultsOut of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62–11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38–1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.ConclusionsA potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.
Highlights
Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions
A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone
When comparing antidepressants taken as a whole with all other drugs in VigiBase®, we found a significant increased Reporting Odds Ratio (ROR) for all subtypes of movement disorders, with the highest association with bruxism and the lowest with tics
Summary
Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The objective of this study was to assess the putative association of each antidepressant and antidepressants’ classes with movement disorders. Antidepressants are one of the most frequently prescribed drug classes in Western countries [1,2,3]. Antidepressants act mainly through the monoamine neurotransmitters, serotonin and noradrenaline [4, 5] They can induce several adverse drug reactions [6], including digestive disorders, sexual dysfunction, fatigue or sleepiness, and hyponatremia, hepatitis [7], or bleeding. Movement disorders are clinical syndromes with either an excess or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity They include extrapyramidal symptoms (akathisia, tardive dyskinesia, dystonia, and parkinsonism) and a wide range of disorders, from tremor to tics and bruxism, to name a few. The frequent use of psychoactive comedications prone to induce movement disorders, such as antipsychotics, mood stabilizers or antiepileptics, in patients receiving antidepressants, makes it difficult to precisely assess the level of imputability [8]
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