Abstract
To The Editor:
A
Raynaud's phenomenon (RP) is a peripheral vasculopathy characterized by recurrent reversible episodes of vasospasm, which are triggered by cold and emotional stress. Color changes, including pallor, cyanosis, and erythema, are observed, and patients may have complaints of numbness and pain. Vascular, neuronal, and intravascular abnormalities have a role in its pathogenesis (Herrick 2005).
Some reports described cases with RP induced by ADHD medications including MPH and dextroamphetamine (Syed and Moore 2008; Yu et al. 2010). In this report, we will describe a 14-year-old girl with ADHD who experienced RP during 27 mg OROS-MPH treatment but not during 18 mg treatment.
Case Report
A 14-year-old girl was referred to our outpatient clinic with complaints of inattentiveness, concentration problems, and learning difficulties. She had been receiving low grades in her classes. According to her mother, she had had similar problems since elementary school, but had never had hyperactivity and impulsivity. According to her psychiatric assessment, she was diagnosed with ADHD–inattentive type, and OROS-MPH 27 mg was initiated. At her second visit to our clinic, 4 weeks later, significant improvement was seen in her symptoms of inattention. However, 3 days after she started to take OROS-MPH, she began feeling cold in both her feet and hands. The coldness in her feet and hands was occurring 3 hours after drug intake, and went on for 12 hours. We decided to discontinue OROS-MPH for 2 days, and her complaint improved. When she restarted taking OROS-MPH, her symptoms of coldness reemerged. Then we decided to taper the dose of OROS-MPH to 18 mg. On this dose, she did not experience coldness in her feet and hands, so we decided to continue her treatment in this dosage.
During her physical examination, her toes and fingers were cold to the touch but ulceration, necrosis, and skin discoloration were not observed. A rheumatologist found no joint stiffness, rash, arthralgia, fatigue, fever, or nail changes. The patient reported no drug allergies. There was no family history of connective tissue diseases. Laboratory investigations of rheumatic illness, including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and antinuclear antibodies (ANA), were unremarkable. In order to exclude peripheral vessel diseases, a Doppler ultrasound examination was made before and after the administration of OROS-MPH, and the patient's blood flow velocity was found to be in the normal range.
Discussion
The development of RP following challenge–dechallenge–rechallenge with OROS-MPH treatment and complete resolution after its discontinuation is suggestive of a causal effect. Our patient experienced RP while taking OROS-MPH 27 mg, but not while taking 18 mg, suggesting a dose-dependent side effect. The Naranjo probability score was 8, defining a probable adverse reaction (Naranjo et al. 1981).
In the literature, there are a limited number of reports on the association between RP and stimulant treatment (Goldman et al. 2008; Syed and Moore 2008; Yu et al. 2010). Syed and Moore (2008) described two pediatric cases with ADHD who developed RP during MPH treatment. Yu et al. (2010) also reported four boys with ADHD who experienced vascular changes in their hands and/or feet while taking psychostimulants. In a retrospective case-control study, Goldman et al. (2008) investigated the relationship between stimulant treatment and RS, and found a significant association between use of stimulants and the presence of RS. All these findings suggest an association between development of RP and stimulants.
The mechanism of RP is suggested to be caused by the imbalance between vasoconstriction and vasodilatation (Herrick 2005). MPH blocks the transport of both dopamine and norepinephrine, and affects both the dopaminergic and noradrenergic systems (Engert and Pruessner 2008). RP associated with MPH is suggested to be caused by stimulation of dopaminergic and noradrenergic systems, which in turn causes release of catecholamines, and promotes vasoconstriction (Goldman et al. 2008).
Physicians should be aware of this rare symptom when prescribing psychostimulants for the treatment of ADHD.