Chapter 5-The Physician's Guide to HD
Pharmacotherapy of Depression
If the patient's depression is accompanied by delusions, hallucinations, or significant agitation, it may be necessary to add an antipsychotic medication to the regimen, preferably in low doses to minimize the risk of sedation, rigidity, or parkinsonism.
If the neuroleptic is being used for a purely psychiatric purpose, and is not required for suppression of chorea, the physician may want to prescribe one of the newer agents such as risperidone (Risperdal), olanzepine (Zyprexa), or quetiapine (Seroquel). These drugs may have a lower incidence of side effects and appear to be just as effective.
Among the older neuroleptics, high potency agents such as haloperidol (Haldol) or fluphenazine (Prolixin) tend to be less sedating, but cause more parkinsonism.
Lower potency agents such as thioridazine (Mellaril) may aid with overactivity and sleeplessness, but tend to be constipating and can cause orthostasis.
Benzodiazepines, particularly short acting drugs such as lorazepam (Ativan) may be another good choice for the short-term management of agitation.
In any case neuroleptics and benzodiazepines used for acute agitation should be tapered as soon as the clinical picture allows.
Manic patients with HD who have delusions and hallucinations may require a neuroleptic, and patients who are very agitated may need a neuroleptic or a benzodiazepine for immediate control of these symptoms.
As discussed for depression, the doctor may wish to prescribe one of the newer antipsychotics which have fewer parkinsonian side effects, such as risperidone, olanzepine, or quetiapine.
In cases of extreme agitation, a rapidly acting injectable agent, such as droperidol (Inapsine) or lorazepam may be necessary.
Finally, ECT is known to be a very effective treatment for idiopathic mania and should be considered when other treatments fail, or when the individual is extremely dangerous.
Delirium, an abnormal change in a patient's level of consciousness, may result from a variety of toxic, structural or metabolic causes.
Delirious patients may have waxing and waning of consciousness, may be agitated or lethargic, and frequently have disturbed sleep. Patients in the later stages of HD, are particularly vulnerable to delirium.
Common causes of delirium in HD include prescription medications, particularly benzodiazepines and anticholinergic agents, alcohol or illicit drugs, and medical problems such as dehydration and respiratory or urinary tract infections.
It is important to ask about over the counter medicines such as cold tablets and sleep aids, which patients and families may forget to mention.
Subdural hematoma, due to a recognized or unrecognized fall should also be considered if the patient suffers a sudden change in mental status.
Delirium can also come about gradually as an underlying problem worsens. For example, a dehydrated patient may no longer be able to tolerate his usual medication regimen. Delirium can also be mistaken for a number of other conditions in HD.
As mentioned previously, it may be accompanied by hallucinations or paranoia. Clinicians usually expect delirious patients to exhibit agitation
or hyperarousal and may overlook the delirious patient who is
somnolent or obtunded. Such patients may seem depressed to their families, but when questioned will not report a low mood.
Physicians should consider a diagnosis of delirium whenever confronted with an acute behavioral change in someone with HD and should review the medication list, examine the patient, and obtain necessary laboratory studies, including a toxicology screen if indicated.
Identification and correction of the underlying cause is the definitive treatment for delirium. Low doses of neuroleptics may be helpful in managing the agitation of a delirious patient temporarily. (end)
HALLUCINATIONS AND PSYCHOSIS
The term hallucination refers to any perceived sensation which is not real. This could take the form of visual apparitions, imagined voices, non-existent odors, or odd sensations on the skin. In Parkinson's disease, hallucinations are almost always visual in character and are usually due to the effects of dopaminergic antiparkinson medications.
Drug-induced hallucininosis may begin with vivid or disturbing dreams. Often hallucinations occur in low light situations, and when the individual is going from one state of consciousness to another, such as waking from sleep.
Someone might "see" a relative in the bedroom upon awakening, but then realize the person is not really present. Something may be seen darting out of the corner of the eye, or crawling bugs will be seen in patterned wall coverings or floor tiles.
Seeing small people, children and animals are common hallucinations. As hallucinations become more vivid, insight into the unreality of the perception is lost, and the patient may be unable to distinguish real from hallucinatory experiences.
Confusion and suspicious paranoid delusions can also occur. The state of confusion and hallucinations is termed psychosis. Unfortunately, a delusional individual often directs his suspicions towards a spouse or other family member. For example, he may suspect the spouse of infidelity or a son or daughter of financial misdeeds.
Uncontrolled hallucinations and psychosis can pose a safety concern. The psychotic person may try to flee the residence, or arm themselves in order to escape or fend off a perceived attacker. Even when safety is not compromised, the agitated behavior and accusations disrupt the entire household or nursing care facility.
Hallucinations and confusional episodes most often occur at night; this nocturnal confusion is referred to as sundowning. The altered sleep-wake pattern in Parkinson's disease may also play a role in these events. Perhaps darkness, artificial lighting, and shadows after sunset make individuals more susceptible to visual misperceptions.
Vivid dreams alone usually do not warrant medical therapy. Sleep remedies discussed in the following chapter may be used if necessary. Similarly, occasional visual hallucinations with insight retained may not require any action beyond reassurance.
There are three basic steps in the assessment and treatment of disturbing hallucinations and delusions:
1 determine the probable cause
2 reduce or withdraw the offending medication(s)
3 add an antipsychotic medication
Medications such as levodopa are often the cause of increasing confusion or hallucinations.
Other medications given for reasons beyond the PD, such as narcotic analgesics (pain relievers), can be the cause as well. The list of prescription drugs which can cause psychotic side effects is very long. Some drugs alter the absorption and breakdown of antiparkinson medications, and thus may cause or lessen these side effects.
Hallucinations and confusion can even be triggered by over-the-counter medicines, as occasionally occurs with the cough medicine dextromethorphan.
Some patients suddenly develop these symptoms because of other illness such as an unrecognized urinary tract infection or congestive heart failure. Finally, some individuals develop hallucinations or psychosis in the absence of medications and co-existing illness. This suggests that the patient may have a less typical form of Parkinsonism such as diffuse Lewy body disease.
When hallucinations or delusions become problematic, the patient or care partner should notify the neurologist or primary care physician. If it is determined that the probable source is the antiparkinson medication, the obvious solution is the reduction or discontinuation of one or more of the drugs.
CHOOSING AN ANTIPSYCHOTIC MEDICATION
Some of the milder medications in this category (Haldol)can be used at low doses for short periods of time, but should not be used for prolonged therapy.
An exception is the drug clozapine (Clozaril®). It has been demonstrated to alleviate the psychotic symptoms without worsening the motor problems. Very small doses, ¼ to ½ of a 25 mg. tablet, given at bedtime is a common starting dose.
Higher doses of this medication can cause excessive sedation, drooling and low blood pressure. Unfortunately, the use of clozapine requires frequent blood tests; the medication has been rarely associated with
agranulocytosis, a depletion in the white blood cells which fight infection.
Newer medications such as olanzapine (Zyprexa®) are now being tested to treat psychosis in patients with Parkinson's disease, but the results of clinical trials are not yet published.
The following table summarizes antipsychotic drugs and their relevance to the Parkinson population
ESTABLISHED DRUGS IN THE TREATMENT OF HALLUCINATIONS AND PSYCHOSIS IN PD
NEWER DRUGS WITH UNCERTAIN TOLERABILITY AND EFFECTS IN PD
Both these drugs have been mentioned as being prescribed for HD. Of interest:
-clozapine therapy has been associated with a potentially serious adverse effect, idiosyncratic agranulocytosis. As a result, frequent blood counts are required for patients taking this medication.
Olanzapine and Clozapine: Comparative Effects on Motor Function in Hallucinating PD Patients
Goetz CG, Blasucci LM, Leurgans S, et al
Hallucinations and other behavioral disturbances are seen in approximately one third of patients with Parkinson's disease (PD) treated chronically with dopaminergic agents. The pathogenesis of these hallucinations is unknown although disturbances in the dopaminergic and serotonergic pathways probably contribute to the process. In the past, reducing the dose of the antiparkinsonian medication was the only treatment available that reduced the chance of developing hallucinations.
The introduction of clozapine has allowed patients to continue taking their dopaminergic medication while treating the drug-induced hallucinations. Presently, clozapine is considered the drug of choice in the treatment of PD-associated psychosis. Clozapine is a tricyclic dibenzodiazepine derivative that has high potency in treating psychosis with minimal central dopaminergic antagonism.
Clozapine appears to be more active at the limbic dopamine receptors than at the striatal receptors and does not induce parkinsonism or tardive dyskinesias. In addition, clozapine has been shown to treat some of the movement disorders associated with PD (eg, tremor, dystonia, and dyskinesia) by a direct mechanism that is independent of the antipsychotic effect.
Unfortunately, clozapine therapy has been associated with a potentially serious adverse effect, idiosyncratic agranulocytosis. As a result, frequent blood counts are required for patients taking this medication.
The primary dysfunction responsible for the olanzapine-associated decline was bradykinesia and gait. In addition, clozapine-treated patients showed significant improvement in reduction of hallucinations and overall behavior while olanzapine had no effect.
Although the study was stopped before full enrollment was achieved, the results suggest that olanzapine may exacerbate parkinsonism in patients with PD who have hallucinations in comparison to clozapine. Clozapine therapy appeared to be associated with a modest improvement in parkinsonism and significant improvement in the overall behavioral assessment.
Family Experiences Zyprexa (olanzapine)
My son was also on Zyprexa (olanzapine) for about three weeks recently
(for manic depression/bi-polar disorder) and then the psychiatrist got a
warning about the probability of children and youth having seizures while
taking it. She immediately pulled him off. This was only about a
month-and-a-half-ago that the warning came out. Unfortunately the loss of inhibitions is just another HD-affected behavior and probably wasn't caused by the Zyprexa. PhilH
My son was on Olanzapine for quite a while. His psychiatrist put him on it for anger and to help him sleep. However, after having five grand mal sezuires, his neurologist took him off the olanzapine.
He was starting to show signs of dis-inhibiton. Not understanding that it is wrong to walk outside in his undwear etc. He had not been sleeping as well. The psychiatrist put him back on the olazapine.
Within in 24 hours, his body and mind were a mess. He was beating
himself in frustration because his movements were so bad. He could not
walk, talk, speak, he jerked violently, and was screaming at the top of his
lungs. The neruologist told us to get him to the ER. In the ER
they had to give him Ativan to calm his body down. After several days on
the ativan, which he still takes, he is doing better. LorettaC
July 25, 2000
My husband just ended a DBL blind trial for zyprexa....it is given I
believe for mood control... but when given for that Dr's noticed that chorea
was decreased... hence this new trial. Although we didn't REALLY know if
he was on it, I was SURE he was as not only did his chorea DECREASE
but he had the side affects listed alsol swelling and weight gain.
The study was not only to see if it decreased the movements but to see how much could be tolerated. His body did not do well at 15 mg, he blew up like a balloon so they decreased it to 12mg.
After the study it was revealed that he WAS on it and he chose to stay on it . He is now taking 7.5 mg now and we are VERY happy with the decrease in movements and I would recommend it. KEEP in mind it may NOT be for everyone tho.... Hope this helped. PatD
As in almost any drug for HD it's a catch 22 situation...........IF it helps the person you have to consider it but be fully aware of the side effects and since some can be serious (like NMS) closely monitored on the drug!
Some of concern to HD patients is the seizures (younger people put on this drug have experienced seizures and the drug stopped), afffect on body temperature regulations, somnolence (sleepy/inactivity). dizziness, constipation and sensitivity to light. See the dose-dependent table that shows the increase in these side affects depending on dosages taken.
Although all info on this drug talk about weight gain, none talk about an increased appetite. From some of the descriptions about a sudden healthy appetitie where the pHD is consuming everything in site.........I wonder if they are in the early to mid-stages of HD? It seems a lot of pHD's go through excessive eating during this stage. Kelly ate everything in site during a 2 to 3 year period eating normal meals and snacking non stop all day/night.
Although relating to AD, some good information on causes of some
symptoms and on medications taken in HD
Delirium (hallucinations) Night disturbances
Delirium or acute confusional states are a frequent concomitant presence
in dementing illnesses, reflecting the greater susceptibility of a compromised cerebral substrate to a variety of potential insults.
Infection, cardiopulmonary insufficiency, dehydration, and anemia are
among the most common medical causes of acute confusional states in demented individuals.
In hospitalized elderly patients, prominent risk factors for delirium include
malnutrition, physical restraints, psychotropic drugs, and bladder catheters.
Iatrogenic drug-induced confusional states are a pervasive and largely preventable problem in individuals with dementia; anticholinergic agents, narcotic analgesics, benzodiazepines, and over-the-counter or prescription hypnotic agents should be used only when reasonable alternatives are lacking and the potential benefits outweigh the risks.
AFFECTS OF SUNDOWNING (DARKNESS)
Sundowning behavior refers to episodic confusion and agitation that typically occurs in the late afternoon or evening. Although the exact cause is not known, its increased prevalence in winter months in northern climates and beneficial treatment with bright-light therapy suggests a relationship to circadian timing mechanisms.
Symptomatic pharmacologic treatment is empirically focused on reducing the severity of the agitated behavior, typically with antipsychotic agents, trazodone, or anti-convulsants.