Review On Therapeutic Drug Combination for Pseudobulbar Affect Disorder in ALS Patients

Dr. Erik P. Pioro at the Neurological Institute, Cleveland Clinic in Ohio conducted a review on clinical data supporting treatment with dextromethorphan (DM) hydrobromide combined with quinidine sulfate (Q) for a disorder called pseudobulbar affect (PBA) that can occur in amyotrophic lateral sclerosis (ALS) patients. The study was published in the journal Neurology and Therapy and is entitled “Review of Dextromethorphan 20 mg/Quinidine 10 mg (NUEDEXTA(®) for Pseudobulbar Affect.”

PBA is the result of a neurologic disorder of emotional expression characterized by frequent, involuntary outbursts of uncontrollable laughing or crying, which are disproportionate or unrelated to the situation or patient’s mood. PBA can be embarrassing and distressful. It usually occurs secondary to a neurologic disease or brain injury, and is often mistaken for depression, leading to misdiagnosis and sometimes inappropriate treatment.

PBA has been associated with several conditions including ALS, a progressive neurodegenerative disease characterized by the gradual degeneration and atrophy of motor neurons in the brain and spinal cord that are responsible for controlling essential voluntary muscles, such as the ones related to movement, speaking, eating, and even breathing. ALS patients may become totally paralyzed and the majority of patients die due to respiratory failure within two to five years after diagnosis.

DM is a drug with sedative and analgesic properties, able to block the NMDA glutamate receptor and inhibit the neurotransmitters serotonin and norepinephrine re-uptake. Q is used as an antiarrhythmic agent and it can increase the bioavailability of DM when used together. In October 2010 the U.S. Food and Drug Administration (FDA) approved DM/Q at 20/10 mg twice daily for PBA treatment.

A part of the review focuses on three large-scale DM/Q trials that demonstrate the drug’s efficacy on PBA treatment. All three clinical studies used the Center for Neurologic Study-Lability Scale (CNS-LS), a validated PBA rating scale, to evaluate DM/Q treatment efficacy in patients.

One of the studies was a randomized, double-blind, 4-week trial with ALS patients diagnosed with PBA that showed that treatment with DM/Q 30/30 mg was superior to treatment with the individual drugs, DM 30 mg or Q 30 mg. Furthermore, patients receiving DM/Q were found to experience less PBA episodes. A second trial, based on a double-blind, placebo-controlled, 12-week study of DM/Q 30/30 mg, reported a similar efficacy in patients with PBA and multiple sclerosis (MS), a progressive neurodegenerative disorder that causes impairment in motor function, irreversible neurological disability and paralysis.

A third trial assessing different doses in a 12-week randomized, double-blind study in patients with PBA and ALS or MS (STAR study – NCT00573443) showed that DM/Q at 20/10 and 30/10 mg doses was superior to the placebo control in improving the CNS-LS scores and reducing the PBA episodes. Overall in the three trials, DM/Q was found to be safe and well tolerated by the patients, with acceptable rates of adverse events.

Dr. Pioro highlights that DM/Q is an effective therapeutic combination for PBA treatment and that it is the first pharmacotherapy specifically approved for this purpose. He also mentions in the review that DM/Q is being considered as a therapy for other clinical conditions such as dementia.