Biomedical subjects
Publications and source records attributed to Rajamannar Ramasubbu.
The authors examined variations of serotonin transporter-linked promoter region (5-HTTLPR) functional polymorphism in 26 stroke patients with major depression and in 25 unrelated nondepressed stroke subjects of Caucasian descent. Findings indicate a significant association between 5-HTTLPR short variant genotype and poststroke major depression.
OBJECTIVE: To assess the probability of cerebrovascular adverse drug reactions (CV-ADRs) due to treatment with selective serotonin-reuptake inhibitors (SSRIs) using 2 causality methods. case summaries: Two patients with the possibility of SSRI-related stroke were referred for causality assessment. Causality assessment was performed using an adverse drug reaction probability scale, as well as clinical and radiologic parameters. A 31-year-old white man, who had been receiving paroxetine 200 mg/day over a period of 3 years, developed ischemic stroke involving left middle cerebral artery. The second patient was a 46-year-old white woman with a history of recurrent depression who developed delirium and ischemic stroke while she was taking a combination of paroxetine 50 mg/day, trazodone 200 mg/day, and bupropion 150 mg/day. DISCUSSION: Carotid and cardiothromboembolism were found to be the major etiological factors for ischemic stroke. Accounting for the temporal relation, prior reports of SSRI treatment-associated CV-ADRs, and the pharmacologic action of serotonin on coagulation and the vascular system, the possible contribution of SSRIs to stroke in these patients was considered. An objective causality assessment using the Naranjo probability scale revealed that a CV-ADR was possible. However, the nature of the stroke, plus clinical and radiologic findings, were inconsistent with known pathophysiologic mechanisms linking SSRIs and stroke in these patients. CONCLUSIONS: Causality assessment may improve unbiased recognition, management, and voluntary reporting of infrequent adverse effects such as SSRI treatment-related cerebrovascular accident.
OBJECTIVE: Emerging literature suggests that hypomanic behaviour may be clinically more important than elated mood in spontaneous hypomania. This report describes dysfunctional behavioural activation as a milder expression of antidepressant-associated hypomania. METHOD: Five outpatients with mood disorders developed problem behaviours following antidepressant treatment. These behaviours include gambling, excessive spending, increased sexual activity, excessive shopping and socially inappropriate verbal aggression. These behaviours were not accompanied with noticeable euphoria or persistent dysphoria and were not characteristics of the individual's personality functioning. They were reported by significant others and patients had no history of primary impulsive, substance abuse or personality disorders. RESULTS: The observed antidepressant-associated behavioural activation was suggestive of hypomanic behaviours not of impulse control disorders because of; (a) absence of other accountable mental or medical disorders characterized by impulsivity, (b) the evidence of close association between impulsivity and hypomanic/manic states, (c) increasing awareness of the diagnostic importance of behavioural disturbances in hypomania, (d) the substantial evidence relating antidepressant treatment to the emergence of hypomania, but not to impulse control disorders, (e) the well documented therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in impulse control disorders. CONCLUSIONS: In accordance with the recent proposed revision in the diagnostic criteria of hypomania, the observed dysfunctional behavioural activation during antidepressant treatment may represent milder expression of antidepressant-associated hypomania. More research is warranted to study the behavioural expression of hypomania secondary to antidepressants.
OBJECTIVES: An understanding of cerebro-vascular effects of selective serotonin reuptake inhibitors (SSRIs) is essential, since SSRIs are a widely used antidepressant, serotonin is a vasoactive and thrombostatic amine, and there is a bidirectional relationship between depression and cerebrovascular disease. DATA SOURCES: A MEDLINE search was performed to identify published reports over the period of 1966 through 2003, using the terms SSRIs and antidepressants matched with the terms platelets, coagulation, anticoagulation, bleeding, fibrinolysis, thrombosis, embolism, cerebral ischemia, stroke, cerebrovascular accident, acute and chronic cerebrovascular disease, intracranial hemorrhage, cerebrovascular disorder, and cerebral circulation. Adverse event reports collected from the World Health Organization (WHO), manufacturers, and the Physicians' Desk Reference (PDR) were also examined. DATA SYNTHESIS: Two case-control studies failed to show an association between SSRI use and intracranial hemorrhage, and of these, 1 showed no association with ischemic stroke. Sixteen studies of SSRI treatment in poststroke patients found no significant cerebrovascular adverse reactions. The WHO data have shown several hundred cases of SSRI-associated cerebrovascular disease, but definitive causal relationships remain undetermined. Four cases of vasoconstrictive stroke related to drug interactions between SSRIs and other serotonergic drugs have been reported. PDR and manufacturer reference sources categorized cerebrovascular reaction as an infrequent or rare adverse event related to SSRI use. CONCLUSIONS: Available evidence suggests that SSRI treatment has a very low rate of cerebrovascular adverse reaction. Pharmacovigilance is required in the use of SSRIs in high-risk populations for bleeding and vasoconstrictive stroke. More research is warranted to examine the variability of pharmacologic and genetic factors, depressive illness, and stroke on the antiplatelet and vasospastic effects of SSRIs and their significance to cerebrovascular protection or adverse reactions.
OBJECTIVES: This narrative review examines the evidence and discusses the clinical relevance of depression as a risk factor for stroke morbidity and mortality. It also proposes recommendations for future research. METHODS: We used the Medline computer database to search the relevant original studies published in English from January 1966 to December 2001. Our key words were as follows: depressive disorder, cerebrovascular disease, stroke, vascular risk factors, and mortality. Articles that investigated the relation between antecedent depression and subsequent stroke morbidity and mortality were collected and reviewed. RESULTS: Since 1990, 8 prospective studies have been published. Among these 8 studies, 6 addressed depression and stroke morbidity, 1 investigated the association of depression with stroke morbidity and stroke mortality, and 1 investigated the association with stroke mortality only. Of 7 studies examining the independent effect of depression on stroke morbidity, 6 were positive. With regard to stroke mortality, 2 studies found an independent association between depression and specific stroke mortality. The contributions and methodological limitations of these studies are discussed. CONCLUSIONS: Emerging data suggest an association between depressive symptoms and increased risk for stroke morbidity and mortality. More methodologically sound studies are needed to elucidate causal pathways that link depression and cerebrovascular disease. They are also needed to determine the effect of depression intervention on reducing the risk of cerebrovascular events. Information on author affiliations appears at the end of the article.
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OBJECTIVE: To examine the efficacy of second-line augmentation with noradrenergic antidepressants (NAs) in depressed patients who partially responded to lithium augmentation of selective serotonin-reuptake inhibitors (SSRIs). CASE SUMMARY: Six patients with major depression or double depression (major depression and dysthymia) who were partially responsive to lithium and SSRI treatment were given either bupropion or desipramine, in an open clinical manner. Improvement was determined and rated by a psychiatrist based on clinical judgment guided by the Clinical Global Impression (CGI) improvement scale and by the Global Assessment of Functioning (GAF) as described in Axis V in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: Among the 6 depressed patients with partial remission (much improved in symptoms and moderate functional improvement: CGI score 2, GAF score 51-60) while taking the SSRI and lithium combination, 2 showed complete remission (very much improved in symptoms and good functioning: CGI 1, GAF 80-100) and 3 achieved near-complete remission (very much improved in symptoms and significant functional recovery: CGI 1, GAF 61-80) when given either bupropion or desipramine. One patient did not show any additional clinical or functional improvement. Second-line augmentation with bupropion was better tolerated than desipramine. CONCLUSIONS: This clinical observation suggests that second-line augmentation with NAs may be a viable option to optimize recovery in depressed patients with a partial response to lithium augmentation of SSRIs.
This case report suggests that diagnostic difficulties and brain mechanisms related to conversion disorder associated with cerebral lesions differ from those related to conversion disorder without cerebral lesions. A 35-year-old divorced woman was admitted to a psychiatric inpatient unit with multiple physical complaints. The symptoms first appeared 5 years previous and 2 months after a sexual assault. Three years later, she began to experience ill-defined sensory symptoms confined to the left half of her body (splitting the midline). Results of neurologic consultations were equivocal because of the subjective nature of the complaints, which were viewed as conversion symptoms. A magnetic resonance imaging scan demonstrated an old infarct in the right parietal lobe, suggesting a physical origin of the patient's symptoms. However, normal somatosensory-evoked responses from the affected area contributed little to establishing the diagnosis. The results of all further investigations to identify causes of the vascular pathology were negative. The multiple ill-defined somatic symptoms, the distribution of sensory symptoms and the resolution of symptoms with psychotherapy established the diagnosis of conversion disorder superimposed on a pre-existing right parietal lesion. This case highlights the importance of clinical features in establishing a diagnosis such as this. We suggest that reactivation of implicit sensory memories (represented at the thalamic level and resulting from decreased corticofugal inhibitions due to the lesion) may contribute to the formation of sensory conversion symptoms in individuals with parietal lobe lesions.
Pathologic laughing and crying (PLC) is a common distressing and socially disabling condition in stroke patients. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), have been increasingly recognized as the treatment of choice for pathologic crying (PC). However, little is known about etiologies and other treatment options for various clinical manifestations of PLC. This case report illustrates the beneficial effect of lamotrigine, a novel antiepileptic drug with antidepressant and mood-stabilizing properties in post-stroke PLC. A 60-year-old woman developed PLC after an ischemic stroke affecting the left frontal and temporal lobes. She was treated with lamotrigine initially at the dose of 50 mg a day, which was gradually increased to 100 mg a day over a 4-week period. There was a significant and rapid recovery in both laughing and crying components of PCL with lamotrigine treatment. The symptoms of pathologic laughing have shown a better response to lamotrigine than PC. Controlled investigations are needed to evaluate the beneficial as well as the differential effects of lamotrigine on PLC.