fluvoxamine and Amyotrophic-Lateral-Sclerosis

Emotional lability may be a part of the syndrome of pseudobulbar palsy. Here we report our experience with fluvoxamine, a selective serotonin reuptake inhibitor, used to treat 10 patients with emotional incontinence. Over a 7-month period, we studied and treated 10 consecutive patients (mean age, 61 +/- 8 years) attending our department: four had amyotrophic lateral sclerosis (progressive bulbar palsy form), four had clinically definite multiple sclerosis, and two had had strokes. They were given a single evening dose (100 mg) of fluvoxamine. All 10 patients had > 30 affective outbursts daily. It was observed that in 2 to 6 days, all the patients improved, the number of emotional outbursts dropping to none to five per day. This result suggests that the serotoninergic system may be implicated in emotional lability. The short latency of improvement we observed in our patients suggests that the mechanism of fluvoxamine for treating emotional lability differs from its mechanism for treating affective disorders.

Topics: Affective Symptoms; Aged; Amyotrophic Lateral Sclerosis; Female; Fluvoxamine; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis; Selective Serotonin Reuptake Inhibitors; Tomography, X-Ray Computed

Marked reduction of RNA editing at the glutamine (Q)/arginine (R) site of the glutamate receptor subunit type 2 (GluR2) in motor neurons may be a contributory cause of neuronal death specifically in sporadic ALS. It has been shown that deregulation of RNA editing of several mRNAs plays a causative role in diseases of the central nervous system such as depression. We analyzed the effects of eight antidepressants on GluR2 Q/R site-RNA editing in a modified HeLa cell line that stably expresses half-edited GluR2 pre-mRNA. We also measured changes in RNA expression levels of adenosine deaminase acting on RNA type 2 (ADAR2), the specific RNA editing enzyme of the GluR2 Q/R site, and GluR2, in order to assess the molecular mechanism causing alteration of this site-editing. The editing efficiency at the GluR2 Q/R site was significantly increased after treatment with seven out of eight antidepressants at a concentration of no more than 10 microM for 24h. The relative abundance of ADAR2 mRNA to GluR2 pre-mRNA or to beta-actin mRNA was increased after treatment with six of the effective antidepressants, whereas it was unchanged after treatment with milnacipran. Our results suggest that antidepressants have the potency to enhance GluR2 Q/R site-editing by either upregulating the ADAR2 mRNA expression level or other unidentified mechanisms. It may be worth investigating the in vivo efficacy of antidepressants with a specific therapeutic strategy for sporadic ALS in view.

Topics: Adenosine Deaminase; Amitriptyline; Amyotrophic Lateral Sclerosis; Antidepressive Agents; Arginine; Cyclopropanes; Desipramine; Fluoxetine; Fluvoxamine; Glutamine; HeLa Cells; Humans; Imipramine; Milnacipran; Morpholines; Paroxetine; Reboxetine; Receptors, AMPA; RNA Editing; RNA-Binding Proteins; RNA, Messenger

A 57-year-old man with amyotrophic lateral sclerosis (ALS) was admitted because of depressive state. Selective serotonin reuptake inhibitor (SSRI), an antidepressant, was started on the admission day. The throbbing headache in the right temporal region appeared on day 3, and an analgesic drug was not completely effective. Serum sodium value on admission was 131 mEq/l. After SSRI was started the hyponatremia rapidly progressed, and it became 112 mEq/l on day 4. SSRI was discontinued, and headache disappeared; serum sodium was improved to 129 mEq/l. It has been reported that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may be associated with ALS. We consider that subclinical SIADH was manifested by SSRI in this case. SSRI seems to be a cause of headache, since headache disappeared completely by discontinuation of SSRI.

Topics: Amyotrophic Lateral Sclerosis; Antidepressive Agents, Second-Generation; Depression; Fluvoxamine; Headache; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors