Diagnosis and Treatment of Restless Legs Syndrome in Psychiatric Practice
By Hochang Benjamin Lee, MD |
September 8, 2009
Dr Lee is associate director of research development in psychiatry in the division of geriatric psychiatry and neuropsychiatry, department of psychiatry and behavioral sciences, Johns Hopkins University School of Medicine, Baltimore. He reports that he has received research support from GlaxoSmithKline.
Effect of psychiatric medications
Because RLS and psychiatric disorders are frequently comorbid, give careful consideration when choosing a medication for RLS in a patient with a psychiatric disorder. Many psychiatric medications can affect RLS symptoms. However, other than a number of case series or anecdotal reports, few studies have examined the direct effects of psychiatric medications on RLS symptoms, although several have examined the effect of these medications on the severity of PLMS. While PLMS occur in at least 80% of RLS patients and correlate with RLS severity, it is unclear whether medication effects on PLMS can be used to infer the effect of psychiatric medicine on RLS.
Predictably, all typical antipsychotics with dopamine(Drug information on dopamine) receptor blocking properties exacerbate PLMS.35 Commonly used antiemetics, such as metoclopramide(Drug information on metoclopramide), promethazine, and prochlorperazine(Drug information on prochlorperazine), also exacerbate RLS symptoms because of their dopamine receptor blocking properties. With their lower binding affinity for the dopamine D2 receptor, newer atypical antipsychotics are less likely to exacerbate PLMS. However, exacerbation of RLS-like symptoms with olanzapine(Drug information on olanzapine)36 and risperidone(Drug information on risperidone)37 has been reported. Insufficient data are available about effects of clozapine(Drug information on clozapine), quetiapine(Drug information on quetiapine), and ziprasidone on RLS or PLMS. Aripiprazole(Drug information on aripiprazole), a partial dopamine agonist, theoretically might have a favorable effect on RLS symptoms, but a systematic study is needed.
Although it has been suggested that various tricyclic antidepressants (TCAs) and SSRIs exacerbate RLS or PLMS, the specific mechanisms are unknown.38-41 In contrast, bupropion, a dopamine agonist, might alleviate RLS symptoms.40 The effect of trazodone and mirtazapine(Drug information on mirtazapine) on RLS symptoms is unclear.
Given the effects of these medications on RLS symptoms, it is important to screen for RLS symptoms before starting antidepressant therapy. For a patient with severe RLS and mild depressive symptoms, it is reasonable to treat RLS first to see whether improvements in sleep and energy lead to resolution of depressive symptoms. When treating depression in patients with severe RLS, consider trying a non-SSRI or non-TCA (eg, bupropion) first. Keep in mind that there are no comparative studies of the efficacy and safety of bupropion and SSRIs in comorbid depression and RLS.
In the treatment of mood disorders, especially bipolar disorder, anticonvulsants (eg, valproic acid) are commonly prescribed to stabilize mood. In general, anticonvulsants that are associated with pain relief ameliorate RLS symptoms. Gabapentin(Drug information on gabapentin) and carbamazepine(Drug information on carbamazepine) are second-line agents in the treatment of RLS, and valproic acid might also be helpful in reducing RLS symptoms.16,25,26 While anecdotal reports of RLS induced by lithium(Drug information on lithium) exist, no systematic study has tested the effect of this agent on PLMS or RLS symptoms.42
Benzodiazepines and hypnotics are often prescribed to treat insomnia related to psychiatric disorders; these medications have not been shown to exacerbate PLMS. Among them, clonazepam(Drug information on clonazepam) is preferred over short-acting benzodiazepines for the treatment of anxiety and insomnia in patients with RLS because of its longer half-life. However, studies that examined the effect of clonazepam on PLMS and RLS did not find a consistent reduction in PLMS; patients instead reported a more restful sleep.43
Antihistamines are commonly taken for sleep problems. However, certain drugs in this class, including diphenhydramine(Drug information on diphenhydramine), can exacerbate PLMS and RLS and should be avoided.
Dopamine agonists and psychiatric symptoms
In randomized, double-blind, placebo-controlled trials of pramipexole(Drug information on pramipexole) or ropinirole(Drug information on ropinirole) for RLS treatment, none of the participants treated with dopamine agonists experienced neuropsychiatric symptoms. Use caution when interpreting the clinical safety data because the RLS treatment studies have systematically excluded patients with psychiatric comorbidity. Therefore, clear data do not exist on the potential neuropsychiatric adverse effects of dopamine agonist treatment of RLS in patients with comorbid psychiatric disorders.
Dopamine agonist treatment of Parkinson disease has been associated with hallucinations, delusions, confusion, and mania.44,45 Lower recommended doses of dopamine agonists seem less likely to induce psychotic symptoms in RLS patients without psychiatric comorbidity. However, the potential for inducing or exacerbating behavioral symptoms in RLS patients with psychiatric disorders from dopamine agonist therapy cannot be ignored.
Compulsive gambling,46 overeating,47 and hypersexuality48 have also been associated with dopamine agonist treatment of Parkinson disease and, to a lesser degree, RLS. Therefore, those clinicians who treat RLS in patients with impulse-control disorder or affective disorders (eg, bipolar disorder) should be aware of the potential for initiating or exacerbating impulsive behavior or mood symptoms.
Another problematic adverse effect of dopamine agonist treatment of Parkinson disease is daytime somnolence. Sleep attacks (ie, sudden and overwhelming sleepiness without awareness of falling asleep), particularly while driving, have been described in patients taking dopamine agonists and represent a serious public safety issue.49,50 Therefore, dopamine agonists should be prescribed and titrated with caution, especially for older patients who have RLS, to reduce the adverse effect of daytime somnolence.
RLS is a common treatable disorder, closely associated with depression and anxiety in both clinical populations and the community. Given the potential impact of various psychiatric drugs on RLS symptoms, medications need to be chosen judiciously to avoid exacerbating RLS symptoms. As more patients with psychiatric disorders receive a diagnosis of RLS and are treated with dopamine agonists, uncommon, yet problematic psychiatric adverse effects related to pharmacotherapy for RLS may develop. Future systematic studies are warranted to guide the optimum treatment of RLS in patients with psychiatric conditions, particularly depression and/or anxiety.
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