fluvoxamine and Parkinson-Disease

Nonmotor symptoms (NMS) such as anxiety, depression, and cognitive deficits are frequently observed in Parkinson's disease (PD) and precede the onset of motor symptoms by years. We have recently explored the short-term effects of Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) on dopaminergic neurons in a parkinsonian rat model. Here, we report the long-term effects of Fluvoxamine, on early-life stress-induced changes in the brain and behavior. We specifically evaluated the effects of Fluvoxamine on brain mechanisms that contribute to NMS associated with PD in a unilateral 6-hydroxydopamine-lesioned rat model. A 14-day early postnatal maternal separation protocol was applied to model early-life stress followed by unilateral intracerebral infusion of 6-hydroxydopamine (6-OHDA) to model aspects of parkinsonism in rats. The anxiolytic, antidepressant, and cognitive effects of Fluvoxamine were confirmed using the elevated plus-maze (EPM) test, sucrose preference test (SPT), and Morris water maze (MWM) test. Further to that, our results showed that animals exposed to early-life stress displayed increased plasma corticosterone and malondialdehyde (MDA) levels which were attenuated by Fluvoxamine treatment. A 6-OHDA lesion effect was evidenced by impairment in the limb-use asymmetry test as well as decreased dopamine (DA) and serotonin levels in the striatum, prefrontal cortex, and hippocampus. These effects were surprisingly attenuated by Fluvoxamine treatment in all treated rats. This study is the first to suggest that early and long-term treatment of neuropsychological diseases with Fluvoxamine may decrease the vulnerability of dopaminergic neurons that degenerate in the course of PD.

Topics: Animals; Disease Models, Animal; Fluvoxamine; Male; Parkinson Disease; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Stress, Psychological

Topics: Age Factors; Aged; Comorbidity; Depressive Disorder; Female; Fluvoxamine; Humans; Parkinson Disease; Parkinson Disease, Secondary; Selective Serotonin Reuptake Inhibitors

In two patients with severe Parkinson's disease (PD) whose response to levodopa had decreased, the parkinsonian motor symptoms responded to acute and maintenance unilateral electroconvulsive therapy (ECT). Case 1 relapsed while taking antiparkinsonian medication 2 and 3 months after two brief courses of ECT. After another relapse, he received maintenance ECT and stayed well for 13 months. Case 2 relapsed 4 months after a course of ECT. Acute and maintenance ECT induced improvement for 14 months. Further relapses were treated with brief courses of ECT followed by maintenance ECT. Three and 4 years after their first ECT, the parkinsonian motor symptoms in these two patients are still markedly improved. Neuropsychological assessments did not suggest ECT-induced long-term cognitive impairment. We conclude that maintenance ECT should be considered in PD patients who relapse after having responded to an initial course of ECT. There is an urgent need for controlled studies.

Topics: Adult; Antiparkinson Agents; Electroconvulsive Therapy; Female; Fluvoxamine; Functional Laterality; Humans; Informed Consent; Levodopa; Male; Parkinson Disease; Selective Serotonin Reuptake Inhibitors

A 55-year-old man presented with a 5-year history of Parkinson's disease and a 6-month history of major depression. The patient's depressive symptoms responded to treatment with fluvoxamine, a selective and potent serotonin reuptake inhibitor. Tryptophan depletion testing, which acutely lowers central serotonin levels, caused a brief exacerbation of the depressive illness, which resolved upon tryptophan repletion. Serotonergic dysfunction may be an etiologic factor in depression that occurs in Parkinson's disease.

Topics: Depressive Disorder; Fluvoxamine; Humans; Male; Middle Aged; Neurotransmitter Uptake Inhibitors; Parkinson Disease; Serotonin; Tryptophan