Restless legs syndrome (RLS) as well as the periodic limb movement disorder (PLMD) are common primary disorders in the general population. They can also occur secondarily or exacerbate as a result of psychotropic medication. According to case reports or case series RLS or PLMD can aggravate due to treatment with antidepressants, antipsychotics or lithium. RLS can also occur during withdrawal from opioids. Especially the tricyclic antidepressants clomipramine and imipramine have been associated with elevated periodic limb movements as well as the tetracyclic antidepressants venlafaxine, SSRIs and SNRIs which also have been associated with RLS. RLS seems to occur mostly during treatment with mirtazapine. Amitriptyline, nortriptyline, doxepine and trazodone show neutral effects whereas bupropion has neutral to beneficial effects on PLMS/ RLS.

When withdrawn from opioid treatment, transient discontinuation effects could occur as well as an existing RLS could be unmasked.

When examining a maintaining or newly occurring insomnia, possible treatment side effects in form of RLS/ PLMS should be considered. If possible, substances should be replaced: antidepressants of other groups could be used; antipsychotic medication could be switched to antiepileptics or benzodiazepines. If the psychotropic medication cannot be changed, RLS and PLMD have to be treated on their own, if possible with dopaminergic substances which are the first-line treatment in RLS.