The Hospice Clinician Blog

Proton Pump Inhibitors and Hospice Patients

In my original article, three years ago, I described the patterns of indiscriminate overuse of the proton pump inhibitor drugs (PPI medications) and cited some medical literature reports of increased risk of hip fracture and increased risk of infection related to their long-term use. At that time, I cautioned against the use of the PPI drugs for periods longer than 3 months for most patients and advocated for withdrawal of PPI therapy in any patient on long-term therapy that had not exhibited recent symptoms and had no established indication for continued use.   Now, the issue of PPI potential adverse effects is in the news again.

Fast-forward three years: Last month, the FDA issued a formal warning regarding the increased risk of fractures of the hip, wrist, and spine with long-term use of the PPI drugs (based on review of epidemiological studies). The majority of the studies evaluated individuals 50 years of age or older and the increased risk of fracture was primarily observed in this age group. The greatest increased risk for fractures in these studies involved people who had been taking prescription proton pump inhibitors for at least one year. FDA recommends healthcare professionals should consider whether a lower dose or shorter duration of PPI therapy would adequately treat the patient's condition.

An article in last year's American Journal of Gastroenterology (March 2009) amplified upon additional concerns associated with long-term PPI usage. The researchers from the University of Michigan, Department of Family Medicine, strongly advocated for clinicians to use the lowest dosage of PPI drug necessary for the shortest period of time to achieve the desired therapeutic goals. Concerns cited for their recommendation included the following risks; potential for Clostridium difficile-associated diarrhea, community acquired pneumonia, hip fracture, and vitamin B12 deficiency. The authors suggested the use of "step-down", or "on-demand" PPI therapy for treatment of GERD, and eliminating the use of PPI drugs for prophylaxis of "stress" ulcers outside of the ICU. 

The conclusion of the article in The Clinician Newsletter from 3 years ago is still appropriate today. Given the concerns over potential adverse effects, the documented overuse of these drugs, and the relatively high cost, clinicians should consider using these drugs at the lowest effective doses for the shortest possible durations. Serious consideration should be given to withdrawal of PPI therapy in any hospice patient on long-term therapy who has not exhibited symptoms within the previous 3 months and has no established indication for continued use.  

Some of the commonly used PPIs are listed below (many are now available in OTC formulations): Aciphex (rabeprazole), Nexium (esomeprazole), Prevacid (lansoprazole), Prilosec (omeprazole), Protonix (pantoprazole)

Discontinuing Drugs in Hospice: Which ones need to be tapered? Part 2

Continued from Part 1 of Discontinuing Drugs in Hospice

There is no hard and fast rule regarding drug discontinuation. The plan for each hospice patient will depend upon their individual condition, prognosis, and goals of care. In many cases, the doses being used will not be great enough to result in any significant withdrawal or rebound effects upon abrupt discontinuation of the drug. It is important for the clinician to be aware of the potential for these types of drugs to cause adverse effects if withdrawn abruptly. Decisions regarding tapering of medications can then be addressed in light of the hospice patient's current condition, the dosage of medication, and the duration of therapy with the medication. Some strategies for gradual discontinuation have been provided here and should be considered as starting points in a patient's plan for gradual dose reduction. Once the process of gradual dose reduction is initiated, it should be individualized and modified depending upon the patient's response. In dying hospice patients who are no longer able to swallow medication, it is generally acceptable to discontinue many of these medications abruptly.

Beta-blockers (metoprolol, atenolol) are one of the more widely known examples of drugs that usually requires tapering. In general, if beta-blockers are stopped abruptly the patient will be at risk for rebound hypertension, angina, and tachycardia. Patients on higher doses will be at greater risk for those problems. Patients on the lower entry-level doses such as metoprolol 25mg bid probably will not be adversely affected by an abrupt discontinuation. Beta blockers may need to be tapered over 7 to 10 days depending upon the dosage.

Antidepressants may need to be tapered over 3 to 4 weeks (reduced by 25% a week) to avoid withdrawal symptoms. This is true of SSRI type and Tricyclic type of antidepressants. SSRI withdrawal symptoms include: flu-like symptoms (muscle aches, nausea-vomiting, diarrhea), insomnia, irritability, depression, flushing, sweating, dizziness, and "electric-shock" sensations in various parts of the body. Tricyclic withdrawal symptoms are similar to that of the SSRI drugs, but without the dizziness or the "electric shock" sensations. The withdrawal syndrome has been reported most commonly with Paxil and Effexor, but may occur with any antidepressant. Patients on lower doses may have doses reduced by 50% per week over 1 to 2 weeks.

Antipsychotic drugs may need to be tapered over 1 to 2 weeks to avoid withdrawal symptoms that may include: sweating, salivation, runny nose, flu-like symptoms, parathesia, increased urination, vertigo, agitation, anorexia, and psychosis. Antipsychotics may be stopped abruptly if severe adverse effects are present (dystonia, agranulocytosis). If abrupt discontinuation is necessary, withdrawal symptoms may be managed with benzodiazepines or valproic acid.

Anticonvulsants may need to be tapered by 25% a week to reduce the risk of seizures. More rapid tapering may be initiated if there are serious adverse effects present, however, smaller dose reductions may be necessary if seizure control has been poor. Ideally, taper should start after a new agent has been titrated to an effective dose. Gabapentin & Pregabalin withdrawal symptoms may include anxiety, insomnia, nausea, pain, & sweating in addition to seizure activity.

Benzodiazepines when stopped abruptly from moderate to high doses may result in a true physiological withdrawal and may also cause a relapse in the original anxiety symptoms that the patient was being treated for. Symptoms of benzodiazepine withdrawal include: sweating, tremor, agitation, nausea, and tachycardia. At very high doses, abrupt stoppage of the drug may result in seizures. Patients on high doses may need to be tapered over 4 weeks. Those at the low end of the dosage range may not require a taper.

Muscle relaxants, including Baclofen, Carisoprodal, and Tizanidine may need to be tapered over 1 week to avoid symptoms ranging from mild reactions of body aches, anxiety, sweating, and insomnia to severe reactions including hallucinations, hypertension, tachycardia, and seizures. Doses in the lower range are generally associated with only mild reactions upon abrupt discontinuation.

Corticosteroids may need to be tapered to avoid a rebound of symptoms of the underlying condition being treated (flares of rheumatoid arthritis, lupus, dermatitis) as well as to avoid steroid withdrawal symptoms. Steroid withdrawal symptoms include: flu-like symptoms (muscle aches, nausea/vomiting, diarrhea), hypotension, abdominal pain, weakness, and weight loss. Steroid withdrawal symptoms are due to the unmasking of adrenocortical suppression seen with the abrupt stoppage of corticosteroids in patients on long-term therapy. Generally significant adrenocortical suppression is not a concern in patients who have received corticosteroids for 3 weeks or less and have not received a dosage of > 20mg/day of Prednisone or Prednisone equivalent (dexamethasone > 3mg/day). Abrupt cessation in these patients is unlikely to trigger significant steroid withdrawal symptoms. For patients who have been on higher dose steroids or receive courses of therapy longer than 3 weeks, a gradual taper is recommended. Steroid doses may initially be reduced rapidly (by halving the dose every 2 days) until physiological doses are reached (prednisone 7.5mg daily or equivalent), then more slowly (1-2 mg/week) to allow the adrenals to recover.

Clonidine, the antihypertensive medication, may need to be tapered over 2 to 4 days to reduce the risk of a discontinuation syndrome. The discontinuation syndrome with Clonidine consists of rebound hypertension, headache, anxiety, insomnia, sweating, tachycardia, tremor, muscle cramps, hiccups,nausea, and salivation. Rarely, in extreme cases of abrupt withdrawal off of very high doses, encephalopathy, stroke, and death have been reported. The risk of the discontinuation syndrome is greater with oral Clonidine than with the Transdermal patch, however, it is recommended that the patch be tapered or the patient switched to oral and then tapered.

Opioid withdrawal symptoms consist of runny nose, tearing, chills, muscle aches, vomiting, diarrhea, cramps, anxiety, insomnia, and agitation. Rebound pain from the underlying condition being treated may also present. Initial dosage reduction should be at an increments of 25% every 3 days.

Discontinuing Drugs in Hospice: Which ones need to be tapered? (Part 1)

Many hospice clinicians are faced with the task of discontinuing a variety of medications for new admissions to their hospice programs. When a patient enters into a hospice program the goals of care will often change from one of therapeutic-disease modifying medication therapy to one of palliative medicine and comfort care. In order to meet the changing goals, a number of non-palliative, disease modifying and disease preventative types of drugs will be stopped. Clinicians are sometimes not clear on which medications need to be tapered and which ones may be stopped abruptly. Certain medications need to be tapered to reduce the potential for adverse effects such as drug discontinuation syndrome or rebound symptoms from the underlying condition being treated. The need to taper a medication is determined by the specific type of medication, the dosage that the patient is currently receiving, the duration of therapy, and the health condition of the patient. This post will provide some guidance on the types of medications that we need to be concerned about stopping abruptly.

Categories of drugs which may need tapering upon discontinuation include: antiepileptic drugs, antipsychotics, betablockers, opioids, antidepressants, corticosteroids, certain muscle relaxants, and benzodiazepines. Patients on low entry-level doses of these medications usually do not require a taper, however, tapering should be considered for mid-range to high doses of these medications. The longer the hospice patient has been on the drug, the greater the risk for a discontinuation reaction. Discontinuation syndrome risks are generally increased across the board when drug therapy has been in place for 6 months or more. The decision to taper vs. abrupt discontinuation will also be influenced to a great extent by the presence of serious adverse effects to the medication in question. In some cases the severity of medication side effects may be worse than the potential risk of withdrawal or rebound effects associated with abrupt discontinuation. Take a look at the table below for the medications that you should consider tapering. More detailed information about each category will be examined in Part 2 of this blog post, so check back later this week for more information on tapering drugs for hospice patients.

Consider Tapering When Stopping These Drugs:  CATEGORY	MEDICATIONS
Anticonvulsants	Gabapentin (Neurontin), Phenytoin (Dilantin), Pregabalin (Lyrica), Carbamazepine (Tegretol), Levetiracetam (Keppra), Divalproex/valproic acid (Depakote, Depakene), Phenobarbital
Antidepressants	SSRI: Paroxetine (Paxil), Venlafaxine (Effexor), Escitalopram (Lexapro), Citalopram (Celexa), Sertraline (Zoloft) Tricyclic: Amitriptyline (Elavil), Nortriptyline (Pamelor), Doxepine (Sinequan)
Antipsychotics	Haloperidol (Haldol), Risperidone (Risperdal), Olanzapine(Zyprexa), Quetiapine (Seroquel)
Barbiturates	Phenobaribital, Butbarbital (Fiorinal)
Benzodiazepines	Alprazolam (Xanax), Lorazepam (Ativan), Temazepam (Restoril), Triazolam (Halcion), Diazepam (Valium)
Beta-blockers	Metoprolol (Lopressor, Toprol), Atenolol (Tenormin), Propranolol (Inderal)
Clonidine	(Catapres)
Corticosteroids	(Dexamethasone (Decadron), Prednisone
Muscle relaxants	Baclofen (Lioresal), Carisoprodal (Soma), Tizanidine (Zanaflex)
Opioids	All