Although a definite cause and effect relationship cannot be established between clozapine and these adverse events, the temporal relationship between the onset of symptoms and initiation of clozapine and the disappearance of symptoms with clozapine discontinuation would support such a relationship. In addition, no new medications were started during this period, nor were any current medication doses increased. Although the use of crack cocaine has been reported to cause pleural effusions, 8 this is an unlikely etiology in our patient due to the delay in the onset of pleuritic pain following admission and the absence of concomitant respiratory symptoms, such as cough. Until further data are available, clinicians should be advised to strongly consider discontinuation of clozapine therapy in patients who develop severe pulmonary complications. Raynaud's syndrome in a patient treated with milnacipranTO THE EDITOR: Raynaud's syndrome is usually idiopathic; however, a drug-related etiology is possible. We report a case of Raynaud's syndrome possibly induced by milnacipran, a selective and equipotent sero-Downloaded from tonin-and norepinephrine-reuptake inhibitor (SNRI), without postsynaptic activity.Case Report. A 35-year-old white woman smoker with a history of β-blockerinduced Raynaud's syndrome three years previous, was treated for a number of years with zopiclone and prazepam. She then started taking milnacipran 100 mg/d for depression. Two months later she complained of cold hands and Raynaud's syndrome of the index fingers, without any change in dosage of milnacipran. Exposure to cold was not a trigger factor. Capillarioscopy showed evidence of hypoperfusion and excluded chilblains and sympathetic dystrophy. The vascular loops were normal in number but poorly marked, as seen in ergotism. Investigations for autoimmune diseases were negative. Drug-related etiology was therefore suspected and milnacipran was discontinued, but zopiclone and prazepam were continued. The Raynaud's syndrome symptoms progressively disappeared after one week. There was no rechallenge with milnacipran. Discussion.Although another etiology could not be formally eliminated, milnacipran-related etiology was possible because of the temporal association between milnacipran and Raynaud's syndrome. The symptoms of Raynaud's syndrome began two months after starting milnacipran and disappeared after milnacipran was withdrawn. The patient experienced a first episode of β-blocker-induced Raynaud's syndrome three years earlier, but did not report any Raynaud's syndrome symptoms thereafter. This syndrome has not been reported in association with zopiclone or with benzodiazepines. Milnacipran possibly induced Raynaud's syndrome because of its serotonin-reuptake inhibiting effect, which induces vasospasm.Serotonin (5-hydroxytryptamine) (5-HT) is involved in platelet aggregation; it has a direct vasoconstrictive action on vascular smooth muscle (5-HT 2 ) and an indirect vasodilatory effect by the intermediary of the endothelium, which releases vasodilato...
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