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Lewy Body Dementia – Medication

Introduction

Although there is ongoing, intense research dedicated to elucidating the nature and treatment of dementias, no drugs have been found to consistently slow, stabilize, or reverse the rate of cognitive decline. There are, however, medications for treatment of the symptoms of Lewy body dementia (LBD).

Cholinesterase Inhibitors

Acetylcholinesterase (Ach) is decreased in the brains of people with LBD. Ach inhibitors are the drugs of choice for treatment of hallucinations and agitation in patients with LBD. Fluctuations in cognition may be less frequent, alertness may increase, and memory may improve. There is, however, no evidence indicating that Ach inhibitors alter the course of underlying dementia. Ach inhibitors for treatment of LBD include:

  • Donepezil (Aricept) – may increase concentrations of Ach available for nerve-to-nerve transmission in the central nervous system (CNS), composed of the brain and spinal cord.
  • Rivastigmine (Exelon) – competes with, and inhibits Ach. It’s mechanism of action is unknown. It’s available in both pill and patch forms.
  • Galantamine (Razadyne) – competes with, and inhibits Ach. It’s mechanism of action is unknown. The effectiveness of galantamine lessens as the disease progresses and fewer neurons remain functional. It’s available in immediate-release and extended-release forms.

Antipsychotics, 2nd Generation

Patients with LBD frequently have hallucinations (80 percent) which they act out. It puts both the patient and those around him at risk when unsafe behavior occurs, so the problem must be treated. Older antipsychotic drugs intensify motor symptoms, and must not be used for patients with LBD.

  • Clozapine (Clozaril, FazaClo) – carries a risk of inhibiting the production of white blood cells (agranulocytosis). In the United States, weekly dosing, along with a complete blood count, are required when using this drug.
  • Quetiapine (Seroquel) – is an atypical neuroleptic, which is thought to antagonize dopamine and serotonin. It is also used for insomnia.
  • Aripiprazole (Abilify) – is thought to be a dopamine and serotonin agonist, although that is only a hypothesis.

Antidepressants

Depression is common among people with LBD. Drugs with no anticholinergic activity should be used.

  • Venlafaxine (Effexor) – inhibits serotonin and norepinephrine reuptake.
  • Paroxetine (Paxil, Pexeva) – inhibits serotonin reuptake. It does not affect dopamine or norepinephrine.
  • Sertraline (Zoloft) – inhibits presynaptic serotonin reuptake.
  • Fluoxetine (Prozac) – inhibits serotonin without affecting dopamine or norepinephrine. It has more gastrointestinal side effects than other serotonin reuptake inhibitors, so it is not recommended as first-line treatment for depression with LBD. It can take 4-6 weeks to reach a sustained blood level.

Benzodiazepines

Benzodiazepines appear to effect gamma-aminobutyric acid (GABA)

Clonazepam (Klonopin) is a long-acting benzodiazepine. It’s indications include: myoclonic, akinetic or petit mal seizures, and focal or generalized dystonia (abnormal muscular activity). It is used to wean patients from short-acting benzodiazepines on which they’ve become dependent. Its longer half-life lessens the severity of withdrawal symptoms.

Dopamine Precursors

Patients with LBD have impairment in the motor activity related to dopamine. Their effectiveness is related to the stage of the disease in an individual, becoming less effective as the LBD advances. Whether it has effects on thinking, positive or negative, is controversial.

Levodopa, Carbidopa (Sinemet, Parcopa) is an amino acid which may assist in managing motor fluctuations. Its absorption and effectiveness are strongly by influenced food intake, and are decreased by meals that contain large amino acids.

 

References

  1. McKeith IG, Dickson DW, Lowe J. Diagnosis and management of dementia: third report of the DLB Consortium. Neurology. 2005 Dec 27. 65(12):1863-72
  2. Fernandez HH, Wu CK, Ott BR. Pharmacotherapy of dementia with Lewy bodies. Expert Opin Pharmacother. 2003 Nov 4(11):2027-37
  3. Savica R, et al. Incidence of dementia with Lewy bodies and Parkinson’s disease dementia. JAMA Neurol. 2013 Sep 16.

 

 

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