Letters to the Editor
Minor Strokes Related to Paroxetine Discontinuation in an Elderly Subject: Emergent Adverse Events
Dear Editor:
Abrupt interruption of extended treatment with selective serotonin reuptake inhibitors (SSRIs) may lead to the emergence of discontinuation syndrome. SSRI discontinuation syndrome may manifest with diverse psychological and physical symptoms, including dizziness, shock-like sensory symptoms, anxiety, irritability, agitation, insomnia, and depression (1). Stroke-like neurological symptoms have been reported in 2 patients who developed severe SSRI- induced discontinuation syndrome (2). However, this is the first report that illustrates an elderly man with cerebrovascular disease developing minor strokes following abrupt discontinuation of long-term paroxetine treatment.
Case Report
Mr A, aged 67 years, had chronic depression. He was investigated for dementia secondary to cerebrovascular disease because he developed memory deficits in the background of type 2 diabetes mellitus, hypertension, and coronary artery disease. He was diagnosed with recurrent major depression over 10 years ago and remained normothymic on long-term maintenance treatment with paroxetine 40 mg daily. Review of his history suggested that he had developed minor strokes involving vertebrobasilar artery territory on 2 occasions following abrupt discontinuation of paroxetine. On the first occasion, 24 to 48 hours after accidentally stopping paroxetine treatment, he became anxious, agitated, irritable, confused, showing severe gait ataxia and bilateral motor weakness. He was admitted to a tertiary care hospital and investigated for vertebrobasilar insufficiency. Magnetic resonance imaging (MRI) showed extensive hyperintense T2 signal foci within cerebral white matter, as well as in the left pons, suggesting nonspecific small- vessel ischemic disease. Magnetic resonance angiography revealed mild occlusion or hypoplasia of the right A1 segment of the anterior cerebral artery.
His blood pressure was elevated to 150/100 mm Hg. The symptoms of agitation, anxiety, insomnia, gait ataxia, and bilateral motor weakness were cleared 24 to 48 hours after paroxetine treatment was reinstituted at the previous dosage. Four months later, his cardiologist abruptly discontinued paroxetine treatment, owing to potential anticholinergic and cardiac side effects. The patient was readmitted to the same tertiary hospital with anxiety, agitation, confusion, gait ataxia, and bilateral motor weakness. A repeat MRI showed no progression in cortical white matter and pontine ischemic changes. The discontinuation symptoms, ataxia, and motor weakness resolved within 48 hours after the reintroduction of paroxetine treatment at the previous dosage. Because vertebrobasilar insufficiency lasted for more than 24 hours and brain parenchyma might be irreversibly altered owing to prolonged ischemic attack, the diagnosis of ministroke involving vertebrobasilar territory was considered.
Discussion
The emergence of anxiety, agitation, and insomnia within 24 to 48 hours of abrupt discontinuation of paroxetine maintenance treatment and the resolution of these symptoms after reinstating the previous paroxetine treatment concurs with the diagnosis of SSRI discontinuation syndrome (1). This patient suffered minor strokes involving vertebrobasilar territory, as determined by neurological investigations and stroke neurologists. Hence, in this patient manifested ataxia and motor weakness during a discontinuation phase may indicate minor stroke involving vertebrobasilar territory, rather than the physical symptoms of discontinuation syndrome. Moreover, in the presence of cerebrovascular disease, ataxia and motor weakness could not be considered as discontinuation symptoms. Further, since there was a temporal relation between the onset of minor strokes and the discontinuation of paroxetine treatment on both occasions, it is unlikely that these minor strokes were just coincidental manifestations of the underlying cerebrovascular disease. The possibilities of SSRI treatment– associated cerebrovascular bleeding and vasoconstrictive stroke may be irrelevant: this patient developed minor strokes after the discontinuation of paroxetine maintenance treatment (3,4).
Paroxetine has been frequently implicated in SSRI discontinuation syndrome, owing to its short half-life (5). Cholinergic overdrive activating monoaminergic systems, coupled with hyposerotonergic state after the discontinuation of paroxetine treatment, may be responsible for discontinuation symptoms (6,7). Elevated blood pressure and a possible decrease in cerebrovascular reserve because of activation of catecholamines and resulting anxiety during discontinuation syndrome might have contributed to minor strokes in this patient (8,9). Given the possibility of cerebrovascular events as consequences to anxiety and agitation during discontinuation syndrome, it is imperative to minimize discontinuation symptoms by slowly tapering SSRI treatment in elderly subjects with cerebrovascular disease.
References
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Rajamannar Ramasubbu MD, FRCPC
Calgary, Alberta
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