There are several choices available among the antipsychotic (neuroleptic) drug class for managing psychotic symptoms and end-of-life delirium in hospice patients. The range in cost from the least expensive to some of the most expensive antipsychotics is very broad. Equivalent dose costs can range from as low as $20 per month (Haloperidol 1mg twice a day) to more than $600 per month (Abilify 5mg daily). Efficacy of the various antipsychotic drugs for managing these symptoms in hospice patients is comparable, so the higher cost agents may not be justified when based solely on any clinical evidence of ability to control symptoms. (1, 2) The newer atypical antipsychotics which are significantly higher in cost may have the advantage of lower potential for side-effects, specifically involuntary movement disorders, in certain select groups of patients. This would include patients with a history of drug induced extrapyramidal symptoms (EPS) or a diagnosis of Parkinson’s disease. An atypical antipsychotic may be justified in one of these types of patients. Risperidone should be the primary drug considered in this situation since it is the most cost-effective of the atypical group.
A table of antipsychotic dose equivalents and corresponding estimated costs to the hospice is provided below. The dose equivalents were taken from an article that appeared in the Journal of Clinical Psychiatry in 2003.(3) The dose equivalents were determined by the researcher after an exhaustive review of published studies of fixed dose antipsychotics up until June of 2002. The search included; Medline, the bibliographies of identified reports, published meta-analyses and reviews, Cochrane reviews, Freedom of Information Act material from the FDA, and abstracts from several scientific meetings from 1997 – 2002. The dosage equivalence for the various antipsychotics was reported as “minimal effective dose” equivalents. Most of the reports reviewed to come up with this data were probably not studies that included hospice or terminally ill patients, so keep in mind that “minimal effective” doses in the terminally ill may be lower than that in other populations. The dosage ratios between the drugs, however, would probably still hold true when considering converting from one drug to another.
The table below may be useful in estimating comparative antipsychotic drug costs for a hospice patient, as well as providing an equivalency guide for conversion from one antipsychotic drug to another more cost-effective agent.
*All prices are for the generic version of the drug, except Abilify because there is no generic available at this time.
1) Boustani, M. J. General Internal Med. 2009; 24: 848-853
2) Cochrane Database Syst. Rev. 2007 April 18 (2): CD005594
3) Woods SW. J. Clin. Psychiatry. 2003 Jun;64(6):663-7.
|This piece was a lifejacket that saved me from drwnoing.
Posted 12/27/2012 04:45:47 PM
The first generic versions of Zyprexa® have hit the market, after the FDA approved generic olanzapine tablets and oral disintegrating tablets about 3 weeks ago. This is a welcome addition to the lineup of generic antipsychotics, as Zyprexa® is one of the more expensive antipsychotics on the market.
However, so far the cost savings are minimal. For example, the average wholesale price (AWP) for generic olanzapine 5 mg is $13.20 per tablet, compared to just $14.68 per tablet for brand Zyprexa® 5 mg. The generic olanzapine oral disintegrating tablets (5 mg) are around $14 per tablet, while brand Zyprexa Zydis® 5 mg will cost $15.86 per tablet.
When it is appropriate for your hospice patients, continue to use the less expensive antipsychotics such as haloperidol and risperidone.
|This is really sad.The reosan i worked in the NHS instead of becoming a banker likemy cousin was because it thought it would be less Capitalistic .People not (just) profitsThe NHS has some of the most decent and kind people, that i have ever met.They care.Unlike Capitalists, many of whom don't give a damn about people.We can see that in how they regularly sack thousands.The problem is that Capitalism corrupts everything.It's true that money is important. Financial concerns matter also.However the dignity and high esteem that a human being deservesit totally missing from Capitalism.It's all about the money.
Posted 12/30/2012 03:19:50 AM
|He has been smoking for so long, it would be like tankig his medicine away.Why would you want to take his medicine away just because you don't like something? Think of him.
Posted 8/7/2012 05:12:42 PM
AstraZeneca is adding a new warning to the labels of Seroquel and Seroquel XR. The revised label says Seroquel and Seroquel XR “should be avoided” in combination with other drugs that are known to prolong the cardiac QT interval, including methadone. Other medications to avoid include some antipsychotics (ziprasidone, chlorpromazine, thioridazine), some quinolone antibiotics (levofloxacin, gatifloxacin), and all class IA and class III antiarrhythmics (including amiodarone). According to the FDA, the purpose of the revised labeling is to caution prescribers, and should not be considered a complete ban against prescribing Seroquel with these other medications.
In clinical trials, Seroquel was not associated with a persistent increase in QT intervals, but the QT effect was not systematically evaluated in a thorough QT study. In post-marketing experience, there have been cases of QT prolongation in patients who overdosed on Seroquel, in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval. Previously, Seroquel labeling cautioned against the risk of QT prolongation, but did not list specific medications to avoid in combination.
According to FDA representatives, the label was changed after the FDA received new information about reports of arrhythmia in 17 patients who took more than the recommended dose of Seroquel. Though it should not be a problem at the recommended dosage, it may still be good advice to avoid using Seroquel in combination with agents that prolong the QT interval.
Seroquel should also be avoided in circumstances that may increase the risk of occurrence of torsades de pointes, including a history of cardiac arrhythmias such as bradycardia, and hypokalemia or hypomagnesemia. Caution should be exercised when Seroquel is prescribed in patients at increased risk of QT prolongation (e.g. cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure and heart hypertrophy).
Delirium is an acute state of mental confusion resulting from diffuse brain dysfunction, and occurs in 30-80% of terminally ill hospice patients.
One of the first steps the clinician should take is to determine if one or more prescribed medications may be causing the delirium. In some cases a change in medication or reduction in dosage may result in significant improvement. For example, if morphine induced delirium is suspected, rotation to another opioid may prove to be beneficial without compromising pain control. Morphine has active metabolites, one of which (morphine-3 glucuronide) has been shown to have neuro-excitatory effects that may contribute to delirium. This metabolite accumulates in patients with decreased renal function. A change to an opioid such as methadone which is not renally eliminated and does not have any toxic metabolites would be an appropriate strategy.
Patients receiving multiple drugs that are known to have significant anticholinergic side effects may benefit from reduction of polypharmacy since anticholingeric activity is present in numerous medications and can exert an additive adverse impact on a patient’s mental status (see table below). In addition to the direct effects of these drugs on the central nervous system, they may also contribute to delirium due to peripheral effects on the urinary and G.I. tracts. Severe constipation and urinary retention induced by these drugs in terminally ill hospice patients may also contribute to delirium.
|Antispasmodics||Donnatol (belladonna alkaloids), Levsin (hyoscyamine), Ditropan (oxybutynin)|
|Antidepressants||Elavil (amitriptyline), Sinequan (doxepin), Pamelor (nortriptyline)|
|Drying Agents||Atropine, TransDerm Scop (scopolamine), Levsin (hyoscyamine)|
|Antihistamines||Benadryl (diphenhydramine), Antivert (meclizine), Vistaril/Atarax (hydroxyzine)|
|Antiparkinson Agents||Artane (trihexyphenidyl), Cogentin (benztropine)|
|Antipsychotics||Mellaril (thioridazine), Serentil (mesoridazine), Clozaril (clozapine)|
Benzodiazepines are another class of drugs that have been implicated as a frequent contributor to delirium. (1,2) This is somewhat ironic, because benzodiazepines are often used in clinical practice to treat the anxiety that may precede the onset of more severe mental status changes that is later recognized as delirium. Long-acting benzodiazepines such as diazepam (Valium) pose a greater risk of drug induced delirium in the elderly due to the extended half-life and corresponding risk of drug accumulation. Shorter acting benzodiazepines such as alprazolam (Xanax), lorazepam (Ativan), or oxazepam (Serax) are preferred in this age group. Antipsychotic drugs (haloperidol, risperidone) are considered more effective at treating the symptoms of hyperactive delirium than the benzodiazepines (3, 4).
The corticosteroids, including dexamethasone and prednisone, have also been identified as drugs which may cause or contribute to delirium (5, 6). The adverse effect upon mental status is definitely dose dependent. The Boston Collaborative Drug Surveillance Study found that patients receiving doses less than Prednisone 40mg/day had an incidence of 1.3%, while those receiving between 40—80mg/day had an incidence of 5%. Patients receiving doses more than 80mg of Prednisone per day or its equivalent showed an incidence of 18%. Dexamethasone is used more often than Prednisone in hospice and palliative care patients, being preferred because it has less impact on causing sodium and fluid retention. Dexamethasone 6mg/day is approximately equivalent to Prednisone 40mg/day. Dose reduction may be appropriate in patients being treated with steroids for bone pain or nausea if steroid-induced delirium is suspected. However, in spite of the potential risks for steroid induced delirium when used in high doses, dexamethasone has been very beneficial for the treatment of delirium related to brain tumors. The dosage used for this indication is quite high ranging between 12–24mg/day.
Appropriate medication selection for the symptomatic treatment of delirium is sometimes delayed because the patient’s symptoms are incorrectly assessed initially. Hyperactive delirium may be incorrectly assessed as anxiety and/or insomnia and treated with benzodiazepines. These drugs may worsen the delirium. Hypoactive delirium may be mis-diagnosed as depression and treated inappropriately with antidepressant drugs. Symptoms of grimacing and moaning may present as part of the “disinhibition” feature of delirium. Disinhibition is one of the main features of delirium where previously well-controlled physical symptoms are dramatically expressed. It is important to realize that the expression of these symptoms do not necessarily indicate distress or suffering and may not warrant additional psychotropic medications or increased dosage of existing opioids, both of which may lead to worsening delirium (7).
Antipsychotic drugs are the primary therapeutic agents for the control of hyperactive delirium symptoms including hallucinations, delusions, and agitation. Haloperidol (Haldol) is preferred due to efficacy, low cost, and a variety of dosage forms. Chlorpromazine (Thorazine) is an alternative if more sedation is desired. If there is concern with regard to extrapyramidal symptoms (EPS), as with Parkinson’s patients, risperidone (Risperdal) or quetiapine (Seroquel), may be an appropriate alternative. The cost of Risperdal or Seroquel is 6 to 7 times greater than either of the two older antipsychotic drugs and there is no evidence of greater efficacy than haloperidol. For these reasons Risperdal and Seroquel should be reserved for the subgroup of patients who have not tolerated the older antipsychotic drugs or those at significant risk for serious EPS type reactions. The initial dosage of Haloperidol recommended by the Department of Palliative Care at the M.D. Anderson Cancer Center (University of Texas) is 2mg PO or SC Q6h and 2mg PO or SC Q1h prn (7). The objective of this regimen is to bring agitation under control as quickly as possible to prevent distress to the patient, family, and staff. The dosage is gradually reduced to a minimum effective dosage soon after symptoms are under control. The most useful haloperidol dosage forms are the oral concentrate 2mg/ml and the injection solution in a 5mg/ml concentration. Clinicians should be alert to possible side effects which may include dystonic reactions and/or hypotension. Dystonias are disabling movement disorders characterized by sustained contraction of muscles leading to twisting distorted postures. These reactions may occur when rapidly increasing doses of antipsychotic drugs. Hypotension is more likely to occur with lower potency antipsychotics such as Chlorpromazine.
On rare occasions when antipsychotic drug therapy fails and aggressive sedation is required, a midazolam (Versed) continuous subcutaneous infusion is used at an initial rate of 1mg/hr (7). This is titrated to the patient’s response. Several reports in the literature have demonstrated excellent results with midazolam administered via the buccal route (8, 9). The buccal route represents a more cost-effective and less invasive approach than continuous infusion. This method may be appropriate for quickly getting severe agitation under control in the outpatient setting. An article investigating the pharmacokinetics of buccal midazolam that appeared in the British Journal of Clinical Pharmacology demonstrated a high bioavailability and reliable blood levels following buccal administration of midazolam (10). The starting dosage was 5mg given as divided doses of 2.5mg between the cheek and gums on each side of the mouth. Onset of sedation after administration by this route was 15 minutes. The time to reach maximum blood levels was 30 minutes. Since the drug has a relatively short half-life, the dose may need to be repeated as frequently as every 15- 30 minutes as necessary until an adequate clinical response is obtained. Duration of effect will vary significantly from patient to patient.
Other medications which are used to a much lesser extent for delirium include pentobarbital (Nembutal) and droperidol (Inapsine). These drugs are not specific for delirium but will provide aggressive sedation for patients with intractable symptoms that have not responded to antipsychotic drugs. Pentobarbital rectal suppositories are used in a dosage range of 60-120mg Q4h. Pentobarbital suppositories may provide a reasonable alternative when the oral route is not feasible and the patient or family does not want parenterally administered medications. Droperidol is given either IV or IM in an initial dosage range of 1.25mg to 2.5mg Q4h titrated to the patient’s response.
To conclude, delirium is common in palliative care patients and clinicians should always be alert to the signs and symptoms. Appropriate management should include efforts at both symptom control and identification of the cause and correction, if possible. Always review the patient’s medication regimen closely when delirium is identified and initiate changes as necessary to remove or reduce a possible offending drug. Prompt control of agitation is essential to prevent further distress to the patient, family, and staff. Primary drugs for control of agitation include the antipsychotic drugs; haloperidol (Haldol) or, chlorpromazine (Thorazine) if more sedation is indicated. The newer atypical antipsychotics may be appropriate alternatives for patients exhibiting extrapyramidal symptoms (EPS) or patients at risk for significant involuntary movement disorders (Parkinson’s disease). For patients with intractable hyperactive delirium, midazolam (Versed) may be effective even when treatment with antipsychotic drugs fail.References: (1) Breitbart, Marotta, Platt, et al Am J Psychiatry. 1996;153: 231-237 (2) Slatkin, Rhiner. Amer Academy of Hospice and Palliative Care Medicine/Hospice and Palliative Nurses Association Annual Assembly; January 2005; New Orleans, La. (3) Jackson, Lipman. Delirium in palliative care patients. In: Evidence Based Symptom Control in Palliative Care: Pharmaceutical Products Press; 2000:59-70 (4) Stein, Pirello. Amer Academy of Hospice and Palliative Care Medicine/Hospice and Palliative Nurses Association Annual Assembly; January 2005; New Orleans, La. (5) Hall, Popkin, et al. J Nerv Ment Dis. 167: 229- 236, 1979 (6) Hall, Beresford, Psychiatry; volume 2, 1989, Philadelphia, JB Lippincott; chapter 88 (7) Elsayem, Driver, Bruera. The M.D. Anderson Symptom Control and Palliative Care Handbook. 2nd edition. 2003 (8) Scott, etal Epilepsia 1998; 39(3): 290- 94 (9) Scott, Beag, Neville. Lancet. 1999; 353(9153): 623-6 (10) Schwagmeier, et al. Br J Clin Pharmacol 1998:46: 203-206
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|video on YouTube Kaiser Health Care Speaker video on Youtube Sex, Beer and Death : A blog being a speaker for atnoher Hospice organization Funny Health Care Speaker home on my main
Posted 9/20/2012 10:03:43 PM
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