Therapeutic Use Of DextroMethorphan: Key Learnings From Treatment Of PseudoBulbar Affect
Miller A, Panitch H
J Neurol Sci 2007 Aug 15;259(1-2):67-73
Technion-Israel Institute of Technology, Carmel Medical Center, Rappaport Faculty of Medicine and Research Institute, Center for Multiple Sclerosis, Haifa, Israel
A variety of Neurological conditions and disease states are accompanied by PseudoBulbar Affect (PBA), an Emotional Disorder characterized by uncontrollable outbursts of laughing and crying.
The causes of PBA are unclear but may involve lesions in Neural Circuits regulating the motor output of Emotional Expression.
Several agents used in treating other Psychiatric Disorders have been applied in the treatment of PBA with some success but data are limited.
And, these agents are associated with unpleasant side effects due to nonspecific activity in diffuse Neural Networks.
DextroMethorphan (DM), a widely used cough suppressant, acts at Receptors in the BrainStem and Cerebellum, Brain regions implicated in the regulation of Emotional Output.
The combination of DM and Quinidine (Q), an Enzyme Inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials.
In patients with Multiple Sclerosis and Amyotrophic Lateral Sclerosis and was both safe and effective in palliating PBA symptoms.
In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of Neurological Disease states are ongoing.
Randomized, Controlled Trial Of DextroMethorphan/Quinidine For PseudoBulbar Affect In Multiple Sclerosis
PsuedoBulbar Affect in Multiple Sclerosis Study Group
Panitch HS, Thisted RA, Smith RA, Wynn DR, Wymer JP, Achiron A, Vollmer TL, Mandler RN, Dietrich DW, Fletcher M, Pope LE, Berg JE, Miller A
Ann Neurol 2006 May;59(5):780-7
University of Vermont, Fletcher Allen Health Care, Neurology Health Care Service, Burlington, 05401, USA
To evaluate the efficacy and safety of DM/Q (capsules containing DextroMethorphan [DM] and Quinidine [Q]) compared with placebo, taken twice daily, for the treatment of PseudoBulbar Affect over a 12-week period in Multiple Sclerosis patients.
A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess PseudoBulbar Affect with the validated Center for Neurologic Study-Lability Scale.
Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale.
Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85).
All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p < or= 0.0077), quality of life (p < 0.0001), quality of relationships (p = 0.0001), and pain intensity score (p = 0.0271).
DM/Q was well tolerated; only Dizziness occurred with greater frequency than with placebo.
Results in Multiple Sclerosis patients were similar to those of a previous study in Amyotrophic Lateral Sclerosis.
Demonstrating that DM/Q may be beneficial in treating potentially disabling PseudoBulbar Affect in a variety of Neurological Disorders.
PseudoBulbar Affect In Multiple Sclerosis: Toward The Development Of Innovative Therapeutic Strategies
J Neurol Sci 2006 Jun 15;245(1-2):153-9
Center for Multiple Sclerosis, Department of Neurology, Carmel Medical Center, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, Israel
PseudoBulbar Affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing.
Occurs frequently in patients with a variety of Neurological Disorders, including Amyotrophic Lateral Sclerosis (ALS), Stroke, Traumatic Brain Injury, Dementia including Alzheimer's Disease, and Multiple Sclerosis (MS).
Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated.
Agents used to treat Psychiatric Disorders-particularly Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors-are useful in alleviating PBA, but act on Diffuse Neural Networks rather than targeting those involved in Emotional Motor Expression.
As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them.
DextroMethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the BrainStem and Cerebellum, thus providing the possibility of targeting regions implicated in Emotional Expression.
When administered in a fixed combination with Quinidine, DextroMethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA.
Review Of PseudoBulbar Affect Including A Novel And Potential Therapy
Schiffer R, Pope LE
J NeuroPsychiatry Clin NeuroSci 2005 Fall;17(4):447-54
Texas Tech University, Health Sciences Center, Department of NeuroPsychiatry, 4515 11th Street, Lubbock, TX, USA
PseudoBulbar Affect (PBA) is an Affective Disinhibition Syndrome associated with various NeuroPathologies, which is characterized by involuntary and inappropriate outbursts of laughter and/or crying.
The PBA syndrome can be socially and occupationally disabling, and it is largely unrecognized in clinical settings.
Validated instruments to distinguish PBA from other disorders of Affective Regulation exist and could be used to improve recognition of the disorder.
There is no pharmacological therapy with a Food and Drug Administration indication for PBA, although AntiDepressants and Dopaminergic agents have been reported to show varying levels of treatment success.
Recent evidence suggests that treatment with a fixed combination of Dextromethorphan and the Cytochrome P450 2D6 enzyme inhibitor, Quinidine, can improve PBA.
This review describes the clinical and NeuroPathological features of PBA, and presents an overview of current and future treatment approaches.