Medication Summary
Drugs used to manage psychosis and agitation in patients with dementia are intended to decrease psychotic symptoms (eg, paranoia, delusions, hallucinations) and associated or independent agitation, screaming, combativeness, or violence. The therapeutic goal is increased comfort and safety of patients, families, and caregivers.
In 2008, Adam and Jankovic published a review of therapies for the treatment of motor, psychiatric, behavioral, and cognitive symptoms of HD. They developed a clear visual to depict the suggested algorithm for symptomatic treatment of HD. [13]
There is only one FDA-approved medication for Huntington's disease. Xenazine (tetrabenazine) was approved by the FDA in 2008 and is indicated for treatment of movement disorder (chorea) caused by Huntington's disease. This drug has no impact on dementia or cognitive decline associated with the disease.
Antipsychotics
Class Summary
Choice of agent is based on adverse-effect profile (patient specific). Atypical neuroleptics such as quetiapine and aripiprazole are the best studied. They are initiated at low doses and are given as standing doses rather than as needed. Use the lowest effective dose, and treat emergent adverse effects first by dose reduction. Younger and less frail individuals may tolerate and respond to somewhat higher doses. Periodically consider reducing or withdrawing antipsychotic medications.
Seroquel (Quetiapine)
Highly effective with data that indicates it has a low EPS profile (similar to placebo). Flipside is its initial sedating effect.
Aripiprazole (Abilify)
Mechanism of action is unknown, but is hypothesized to work differently than other antipsychotics. Thought to be a partial dopamine (D2) and serotonin (5HT-1A) agonist, and antagonize serotonin (5HT-2A). Additionally, no QTc interval prolongation noted in clinical trials.
Quetiapine (Seroquel)
Indicated for schizophrenia. May act by antagonizing dopamine and serotonin effects.
Risperidone (Risperdal)
Effective against agitation and psychosis in elderly patients, even at very low doses, which may limit EPS. Binds to dopamine D2 receptor with 20 times lower affinity than for 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of EPS.
Clozapine (Clozaril)
May be a good choice for individuals who cannot tolerate EPS of conventional antipsychotic agents. May inhibit serotonin, muscarinic, and dopamine effects.
Thioridazine (Mellaril)
Medium-potency antipsychotic with less EPS but more sedation than haloperidol. More sedating and may be given at bedtime for a patient with difficulty falling asleep. First-line drug for treatment of evening psychosis (sundowning) or multiple affective symptoms (eg, agitation, anxiety, depressed mood, tension, sleep disturbance, fears) in elderly patients, patients with dementia, or both.
Benzodiazepines
Class Summary
Sometimes not ideal agents for geriatric patients. May have higher likelihood of adverse effects and potentially fewer benefits than antipsychotics; however, can be useful in treating agitation when anxiety is prominent. Most common adverse effects are sedation, ataxia, amnesia, confusion, and paradoxical anxiety. Long-acting agents must be used with caution, and dose increases should be gradual. If benzodiazepines are used for an extended period (eg, 1 mo), they should be tapered rather than stopped abruptly, owing to the risk of withdrawal.
Lorazepam (Ativan)
Sedative hypnotic with short onset of effects and relatively long half-life. By increasing action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. Does not require oxidative metabolism in the liver and has no active metabolites.
Benzodiazepine of choice in the ED; can be given PO, SL (for rapid effect in panic attack), and IM or IV (mixed in same syringe with antipsychotic). Has longer CNS effects than diazepam and is preferred over antipsychotics for treatment of psychosis secondary to acute intoxication with hallucinogens, cocaine, PCP, and stimulants. Can be used as adjunctive therapy in nonorganic acute psychosis in which DOC is a high potency antipsychotic.
Anticonvulsants
Class Summary
Given the limited data, cannot be recommended with confidence for treatment of agitation in patients with dementia. Nonetheless, a therapeutic trial of one of these agents may be appropriate for some patients who are nonpsychotic, especially those who are mildly agitated or unresponsive to antipsychotics. Monitoring patients for symptoms of toxicity and discontinuing administration if a toxic symptom is identified or if no improvement is observed are critical. The more efficacious agents have been the newer ones (ie, zonisamide, oxcarbazepine, levetiracetam), which are GABA modulators and have less toxicity, with no need to monitor levels.
Zonisamide (Zonegran)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence indicates that it is also effective in myoclonic and other generalized seizure types.
Oxcarbazepine (Trileptal)
Indicated for treatment of seizures. Pharmacological activity is primarily by the 10-monohydroxy metabolite (MHD) of oxcarbazepine. May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Anticonvulsant effect also may occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children < 8 y) have a 30-40% increased clearance compared with older children and adults. Children < 2 y have not been studied in controlled clinical trials.
Levetiracetam (Keppra)
Used as add-on therapy for partial seizures. Mechanism of action unknown. Has favorable adverse effect profile, with no life-threatening toxicity reported.
Antidepressants
Class Summary
Patients with depression should be considered for treatment even when the diagnostic criteria for major depression are not met. Evaluate patient for neurovegetative signs, suicidal ideation, and other indicators of major depression because these may indicate a need for safety measures. Successful treatment of depression, partially or fully, can resolve cognitive deficits. SSRIs tend to have a more favorable adverse effect profile than cyclic agents. The choice of an antidepressant generally is based on adverse effect profile and general medical and psychiatric status of each patient. SNRIs, which now include venlafaxine (Effexor XR) and duloxetine (Cymbalta), are first-choice agents.
Paroxetine mesylate (Paxil)
Selectively inhibits presynaptic serotonin reuptake. Besides use in patients with depression, Ranen et al used sertraline in the treatment of severe aggressiveness in HD. Complete cessation of agitative behavior was maintained on follow-up studies.
Venlafaxine (Effexor)
Indicated for treatment of depression. May treat depression by inhibiting neuronal serotonin and norepinephrine reuptake. In addition, causes beta-receptor down-regulation.
Duloxetine (Cymbalta)
Potent inhibitor of neuronal serotonin and norepinephrine reuptake. Antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in CNS.
