Best Practices in Tapering Methods in Patients Undergoing Opioid Therapy

The prescribing of opioids for chronic non-cancer pain has escalated over recent years. This pattern has led to a larger number of patients who require discontinuation of opioid therapy. The purpose of this review was to provide an overview of best practices for tapering opioid therapy in patients. A systematic review of the current literature concerning tapering of opioid therapy was performed from 2000-2013. 24 studies were selected for review. Considerable variation was found with regard to taper rate and duration. Taper rate ranged from an initial 20-50% daily reduction in opioid dose to a 5% reduction in dose every one to four weeks. The most common titration rate was a 10% reduction in the daily dose each day. General themes were to individualize taper parameters to ensure patient compliance and presentation of withdrawal symptoms, to slow the rate of the taper to about 1/3 of the original dose, and advise a referral of addicted and complex patients to appropriate specialists for treatment. The majority of available information on tapering opioid therapy consists of clinical guidelines that have been created based on practice experience. There is a need for additional experimental research to develop a more standardized taper protocol.


Introduction
In recent years the use of opioids in the United States has markedly increased. [1] Much of this increase in use can be attributed to the expansion of conditions that opioids are being used to treat. Initially only used in cases of acute pain and severe chronic cancer pain, developments in the last two decades have resulted in greater use of opioids. [2] During the late 1990s there was liberalization of laws governing opioid prescribing by state institutions. [3] In 2000, the Joint Commission on Accreditation of Healthcare Organizations [4] altered its pain management standards for inpatient and outpatient medical care. Furthermore, there has been increased aggressiveness in pharmaceutical companies' marketing of opioids, greater physician and organization advocacy, and an enhanced patient awareness on the right to pain relief. [5] Studies have also revealed that the use of opioids has increased in the treatment of chronic non-cancer pain. Between 1980 and 2000 an increase from 8% to 16% was observed in the number of patients receiving opioid prescriptions for chronic musculoskeletal pain. [2] Data from the National Ambulatory Medical Care Survey [1] suggest that opioids are prescribed in about 15-16% of all chronic back pain cases.
The sales of opioid analgesics were found to have quadrupled from 1999 to 2010. [5] Sales in the United States of hydrocodone increased by 280%, methadone rose by 1,293%, and oxycodone expanded by 866% from 1997 to 2007. [5] It was estimated that 2.0% of adults in the United States regularly use opioids and that approximately 2.9% use them occasionally. [1] Additionally the estimated number of opioid prescriptions in the United States was over 256 million in 2009. [5] The greater prevalence of these agents requires that clinicians be adept at handling potential problems that could arise from this therapy. One of the most common problems clinicians face with opioid therapy is the development of withdrawal symptoms in patients, upon discontinuation. Withdrawal symptoms result from physical tolerance which is closely associated with regular intake of the medication for chronic conditions. These symptoms may include agitation, dysphoria, tachycardia, tachypnea, rhinorrhea, lacrimation, salivation, chills, piloerection, hyperventilation, mydriasis, muscle aches and spasms, bone pain, yawning, restlessness, anxiety, insomnia, diaphoresis, cramps, nausea and vomiting, diarrhea, abdominal cramping, and fever. [6] These symptoms can result in reduced physical function and often lead to a debilitating experience for patients. The most effective way to prevent withdrawal symptoms upon opioid discontinuation is to taper the medication. [7] 43 Advances in Pharmacology and Pharmacy 1 (2): [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]2013 There are many other pertinent reasons to consider tapering a patient's opioid therapy. The patient may be unable to tolerate the side effects of an opioid medication. The opioid may not be effective in treating the patient's pain. The patient's condition may improve to the point where he or she no longer requires as high a dose, or can discontinue the therapy altogether. Additional reasons to alter therapy consist of the patient experiencing hyperalgesia from the therapy, to improve the patient's mood, and to prevent further therapy in the case of addiction. In patients in whom such a strategy is desirable; it is beneficial to know the optimal parameters of tapering. The purpose of this review was to provide an overview of the best practices for tapering opioid therapy in patients.

Methods
A systematic review of the current literature concerning tapering of opioid therapy was performed from 2000-2013 using PubMed, Ovid, Google Scholar, Cochrane Library, and electronic databases. The key search terms were "opioid," "opioids," "taper," "tapering," "detoxification," "detox," "dependence," "withdrawal," and "weaning." Articles which focused on methadone and buprenorphine as detoxification and maintenance treatments in addicted patients were excluded. This omission was due to the complexity and unique aspects of addiction therapy in these patients. Weaning addicted patients off of opioid therapy is significantly different than in non-addicted patients. As addiction is often handled by specialists, it is beyond the scope of this review. Studies cited in the bibliographies of the articles produced by these searches were also included in the review. Articles were selected based upon relevance and quality and included narrative and systematic reviews, prospective and retrospective studies, and clinical guidelines from US government agencies and expert panels. The selected articles were summarized in a table structured by year of publication, author, title, study design, methods, findings, and source. The results were further divided into subgroups: temporal parameters, complex patients with or without behavioral problems (e.g. opioid addiction), and pharmacologic adjuvants.

Results
Twenty-four articles were selected for this review (see Table 1). Twelve of the articles were clinical guidelines. Of the remaining twelve studies, eight involved pediatric patients in the inpatient setting, and four involved populations that included adults in the inpatient setting.

Temporal Parameters
Several studies indicated that the overall schedule of the taper should be determined on an individual basis. [8][9][10] Some experts have suggested that the longer the patient has been on opioid therapy, the longer the taper should be. [6,8,9,11,12] Patients might require a longer taper because they are more likely to experience withdrawal symptoms. [9] An observational study, conducted by Pederson and colleagues [6], found that the length of the taper was positively correlated with pre-taper dosage (r=0.71, p=0.001) length of pre-taper opioid therapy (r=0.42, p=0.001), and the total number of self-reports of taper-related symptoms (r=0.48, p=0.001).These findings were supported in a later study by the same investigators. [12] Both of these studies were performed in an inpatient setting with patients whose ages ranged from 5 to 64. [6,12] It has also been suggested that patients be placed on medications with long half-lives for the taper, as opposed to short half-lives. [9,10,13,14] Switching patients to agents with long half-lives provides a more stable weaning, as the concentration of the drug is easier to control.
A 2012 review, from American Family Physician, proposed consolidating all of the patient's opioid therapy into a single long-acting medication. [14] However, it has also been suggested that tapering may be performed with short-acting agents. [9] A study by Kral recommended that after conversion to one of the longer half-life medications that a "test dose" or "test regimen" should be implemented with close monitoring. During the first week, dosing should be adjusted to control withdrawal symptoms. The taper regimen should then start after the patient is stabilized. [9] The patient's daily medication schedule should be maintained as long as possible. [9] Furthermore, it was recommended that patients be switched from as needed to scheduled dosing. [9,10] The frequency of the dispensing intervals should vary with the degree of the patient's control over his or her opioid use. Prescriptions should not be refilled if the patient runs out prematurely. [10] Providing the patient and his or her family with information about the taper protocol should help increase the patient's comfort level and compliance.
Findings from the review of the literature also varied with regard to taper rate. A study that utilized information related to weaning in pediatric patients in intensive care units found that the required weaning rate is related to the number of days the child has been on a continuous infusion of opioids and benzodiazepines. [15] The longer the patient has been treated with opioids, the slower the weaning rate should be. [15] A 2012 review by American Family Physician [14] recommended that a rate should be selected that avoids withdrawal symptoms, the loss of patient confidence, or pain escalation. Authors suggested that the rate of opioid tapering should be influenced by specific patient behavior. Rapid tapering, by reducing the original dose by 25% every3 to 7 days, should be effective in weaning patients that express frequent requests for early refills, despite adequate titration of long-acting opioids. [14] Other reasons for this rate include the patient experiencing major adverse effects or intoxication, opioid-induced hyperalgesia, and non-adherence to the pain medication agreement. [14] Gradual tapering, by reducing the original total dose by 10% every 1 to 4 weeks, was indicated for patients in which Best Practices in Tapering Methods in Patients Undergoing Opioid Therapy 44 functional goals are not met and in those who experience persistent adverse effects despite opioid rotation (e.g. nausea, refractory constipation, or pruritus). [14] Guidelines, developed by the Department of Veterans Affairs and the Department of Defense [8], stated that the patient should be tapered at a rate of 20%-50% per week of the original dose, with the goal of minimizing withdrawal effects. It was suggested that the quickest rate of tapering should be 20% of the previous day's dose. [8] Other guidelines from Canadian Family Physician suggested varying the rate of the taper from 10% of the total daily dose every day to 5% every 1 to 4 weeks. [10] Multiple guidelines suggested a 10% reduction in the original dose per week. [16][17][18] For example, in 2010 a Group Health Cooperative [11] recommended the 10% reduction in all patients except those with complex comorbidities, those whose function has not improved, and those who have received long-term therapy. Specifically, it was suggested that patients should be tapered at a 10% dose reduction every 2 to 4 weeks. [11] Furthermore, slower tapers should be used in patients who are anxious about the tapering process, those that have cardiorespiratory conditions, and those who might be psychologically dependent on opioids. [9,10] Similarly, a study in which pediatric patients in the intensive care unit were weaned off both opioids and benzodiazepines found that withdrawal symptom onset was related to the speed of the taper. [19] Withdrawal symptoms were more likely to occur early in tapers with quick rates. [19] One study suggested that patients on doses over 200mg/day of morphine or equivalent could be weaned more rapidly than those at lower doses. [20] Patients experiencing severe withdrawal symptoms or worsening of pain or mood should have their dose be held or increased. [10,16] Once the withdrawal, pain, or mood symptoms have subsided, the taper should be resumed.
Several studies cited the last phase of the taper as being the most difficult to accomplish. [9,10,13,20,21] Once the dose reaches 30-45mg of opioid/day, withdrawal symptoms may become more likely. [9,22] Clinical guidelines from the American Pain Society and the Academy of Pain Medicine [20] reported that these effects increase when the patient reaches dosages of 60 to 80mg/day of morphine or equivalent. The reason for this increase in difficulty is due to the poor ability of the body to adapt to the changes in concentration and receptor activity. Findings from an observational study conducted in 2000, focused on transplant patients in the inpatient setting found that patients experienced the most withdrawal effects 4 days after the taper was completed. [6] Additionally, guidelines from Canadian Family Physician [10] suggest that once a third of the original dose is reached, the taper should be slowed to half of the previous rate. [15] Another study stated that if withdrawal symptoms are encountered, it may be necessary to slow rate of dose reduction from a weekly to monthly rate. [16,18] The entire duration of the taper should normally range between 2 to 3 weeks and 3 to 4 months. [10] In comparison, similar studies from two case reports were found in which patients were weaned off of long-term opioid use. [22] The first was a 17-year-old male cancer patient who was on 180mg of morphine immediate release (IR) every 4 hours for approximately 8 months. The patient's dose was reduced over 2 weeks to 30mg every 4 hours. Then he was shifted to 60mg sustained release (SR) morphine twice daily.
He was subsequently reduced to 10mg SR morphine over the next two weeks. The opioid was then discontinued over the remaining two weeks. The patient did not report any withdrawal symptoms. In the other case, a 65 year-old male cancer patient was taking 90mg of IR morphine every 4 hours for approximately 2 weeks. [22] The patient was then weaned to 30mg IR morphine every 4 hours over 4 months. He was then switched to 60mg SR morphine twice daily, reduced over 2 weeks to 10mg SR morphine, and then discontinued after 1 week. This patient only reported mild self-limiting diarrhea that was not treated.
On the other hand, clinicians have explored methods that combine various recommendations by developing an opioid tapering algorithm. [21] The algorithm was created using non-research-based published guidelines, published research on opioid withdrawal symptoms, clinical experience, and multidisciplinary consultant recommendations. [21] It was designed to be used in patients over the age of five, who were receiving continuous infusion opioids. The investigators stated that key features were that tapering needed to be practical and user-friendly, but would allow for flexibility for taper adjustments based on individual patient response. The investigators felt that only the patient could best determine the acceptable degree of pain relief and side effects. It should be noted that total pre-taper opioid dosage was not used as a basis for determining the length of the taper because it resulted in calculations that were considered to be too complex. Furthermore, the chosen rate of decreasing the dose hourly by 10% was used because it provided for easier calculations and increased the consistency of the taper. The taper was held until the next scheduled decrease if the patient decided not to tolerate the pain or withdrawal symptoms. The investigators felt that holding the taper prevents increases and decreases in the continuous infusion rate, which may cause fluctuations of opioid serum levels and delay the tapering process.
Ongoing assessments of pain and withdrawal symptoms were utilized to determine whether the taper continued to be held at the next scheduled dose decrease or proceeded. If intolerable symptoms continued for two successive scheduled opioid decreases, the taper rate was slowed. If new, persistent, or uncontrolled pain developed, it was treated and the taper was delayed until it resolved. When the patient reached an hourly rate that was at or was lower than 0.5mg of morphine, 0.1mg of hydromorphone, or 5mcg of fentanyl the taper rate was slowed. The rationale for slowing the taper at the end came from suggestions from the literature. [21]

Complex Patients
Several studies recommended that patients that present with behaviors characteristic of addiction to opioids or other substances should be referred to an addiction specialist. [8,10,17,18,20] Guidelines created by the Veterans' Administration and Department of Defense [8] suggested that patients with substance use disorders should have their psychiatric conditions and comorbidities identified and documented. These conditions include the presence of infectious diseases, and conditions such as diabetes and cardiovascular disease that may be related to or affected by the patient's substance abuse. [8] The taper will most likely be unsuccessful in patients who are not following the schedule, or are continuing to abuse opioids. The same guideline recommends that these patients be referred to specialists for detoxification treatment in a primary care setting, followed by possible maintenance therapy. [8,17,20] Guidelines produced by The Agency Medical Director's Group [16] in 2010 suggest that patients whose urine drug screening tests are negative for prescribed opioids, positive for amphetamine or methamphetamine, positive for cocaine or metabolites, positive for non-prescribed prescription drugs, or those positive for alcohol should also be considered for referral to an addiction specialist or drug treatment program. Multiple guidelines recommend that if a patient presents with clearly unsafe or illegal behaviors (e.g. dealing/selling medications, impulse control disorders, or parasuicidal acts), then opioid prescribing should be immediately stopped and withdrawal symptoms should be addressed. [8,10,16,20] They should also be assessed for unmet psychosocial needs or situational stressors. [8] Such stressors include occupational problems, poor social support, problematic family relationships or situations, financial difficulties, inadequate or no housing, and difficulties with the activities of daily living. [8] Guidelines from Canadian Family Physician [10] suggest that patients who are unwilling to comply with the taper should be encouraged to seek medical care at another location.
Additionally the guideline suggested that precaution should be utilized in patients that have unstable medical and psychiatric conditions. These conditions can be exacerbated by tapering, as it can cause anxiety and insomnia. [10] Depending on the circumstances, it may be best to either taper, cease opioid prescribing, or to wait until after consultation for specialty services has been obtained. [10] A pain specialist can help to manage the patients' conditions in addition to their pain management. It was advised that particular caution should be exhibited towards patients with suicidal thoughts. One study on opioid-related overdose deaths in Ontario found that 21% of the deaths were suicides. [23] Therefore, it has been suggested that tapering and discontinuation be initiated in patients if they have no improvement in mood or have decreased pain ratings of at least 30%. [23] Multiple studies also advised that if a patient experiences complex withdrawal symptoms during the taper or cannot tolerate it, then he or she should be referred to a pain specialist or a center specializing in withdrawal treatment. [8,16] It is recommended that the provider remain engaged with the patient through the tapering process and provide psychosocial support as needed. These actions should help to avoid complex situations involving the patient and should increase the taper's chance of success. [8] Guidelines by Canadian Family Physician [23] strongly recommended that benzodiazepines and other sedative-hypnotic medications should be discontinued in patients that will undergo opioid tapering. Discontinuation of these medications is particularly important in elderly patients. Cessation of benzodiazepines helps to minimize falls, sedation, and overdose. [23] It was also recommended that pregnant patients or those planning to become pregnant should undergo opioid tapering and discontinuation. These patients should not be taking opioids because acute withdrawal can cause premature labor and spontaneous abortion. [23] Pharmacologic Adjuvants Withdrawal symptoms may be a common concern in patients who are physically dependent on opioids. [6] These symptoms should be minimal if the patient is tapered slowly enough. However, should they arise, they will be unpleasant, but are not lethal. [6] Common withdrawal symptoms include anxiety, depression, insomnia, decreased appetite, aching in the bones and joints, chills, runny nose, gastrointestinal discomfort, diarrhea, and a craving for opiates. [6] Additional medications can be applied to alleviate and minimize withdrawal symptoms. These symptoms should be managed supportively. Antidepressants may be used to manage irritability and sleep disturbances. [8,16] Additionally, antiepileptic medications (AEDs) can be used to treat neuropathic pain in these patients. [8,16,1,2,3] One review studied the use of AEDs in the treatment of central post-stroke pain. [24] Central pain was defined as "pain initiated or caused by a primary lesion or dysfunction of the central nervous system." Central post-stroke pain is due to neuronal excitability, which is caused by damage to the central nervous system. Lamotrigine, gabapentin, carbamazepine, topiramate, and pregabalin have been suggested as a possible adjunct in the treatment of neuropathic pain. [24,25,26] However, there is conflicting literature with regards to their effectiveness and additional research is necessary to judge their effectiveness. These medications are thought to reduce pain by reducing abnormal neuronal hyperexcitability through modulation of voltage-gated ion channels and by their effects on gamma-aminobutyric acidergic and gultamatergic neurotransmission.
One case report, noted that the coadministration of oxycodone and the sodium channel blocker carbamazepine was effective in treating trigeminal neuralgia. [25] The patient's (a 48-year-old woman) neuralgia was initially treated by carbamazepine dosed at 300 mg every 8 hours. However, this treatment was ineffective, and was replaced by a new treatment regimen in which the carbamazepine was reduced to 200 mg every 8 hours and oral oxycodone was added dosed at 5 mg every 12 hours. This regimen was successful in treating the patient's neuralgia.
Another case report suggested that topiramate could be effective in the treatment of dysaesthetic pain. [26] In this study, a 42-year-old woman with an 8-year history of multiple sclerosis was successfully treated with topiramate dosed at 150 mg/day after unsuccessful attempts to treat the pain with amitriptyline and carbamazepine as monotherapies.
Special care should be taken in the use of these agents in the elderly. These patients are more sensitive to certain secondary effects of AEDs, such as cognitive disturbances, due to pharmacodynamics and pharmacokinetic age-related changes. These changes are significant enough that the use of enzyme-inducing AEDs, such as carbamazepine, phenytoin, phenobarbital, and primidone should be avoided in these patients.
Clonidine can be used to attenuate the autonomic withdrawal symptoms such as hypertension, nausea, cramps, diaphoresis, and tachycardia. [9,11,16] However, a review by American Family Physician [14] suggested that clonidine was ineffective for symptom management. Calcium carbonate and milk of magnesia were offered as treatments for dyspepsia, while promethazine and metoclopramide were also proposed as treatments for nausea. [11] Drugs such as trazodone, hydroxyzine, or diphenhydramine may be used to treat insomnia and restlessness. [9,11] For patients with muscle aches and fever, non-steroidal anti-inflammatory agents can be used to alleviate these issues. [9,11] Furthermore, muscle cramps can be treated with dicyclomine and Pepto-Bismol can be used to treat diarrhea. [9] Finally, it is important to note that withdrawal symptoms should not be treated with opioids or benzodiazepines. [8][9][10]16]

Discussion
The purpose of this study was to provide an overview of what are considered to be the best practices for tapering opioid therapy in patients. There was variation in the parameters of the taper between articles. Some guidelines reported that it was necessary to switch the patient to an agent with a long half-life, while others did not. [9,10,13,14] Reasons for the disagreement in findings are difficult to determine. However, these disagreements came from guidelines based upon clinical expertise. A plausible explanation is that the healthcare professionals who developed these documents had varying clinical experiences. The taper rate had the most variation by far. Rates ranged from an initial 20-50% daily reduction in opioid dose to a 5% reduction in dose every one to four weeks. [8,10] Reasoning for these rates was often not provided. Studies that offered their rationale stated that it came from established guidelines, or was per protocol of the institution. [6,[12][13][14][15]19,27] The one study that experimentally developed its rate, selected it based upon ease of use and consistency. [21] However, there were several consistencies between the studies. Although the rates varied, tapers were designed with the goal of minimizing the occurrence of withdrawal symptoms.[8-10,14,16] The occurrence and severity of withdrawal symptoms are the primary means of assessing the taper's success. This practice logically follows into another consistency: the need to be able to individualize tapers. Some patients may be more prone to exhibit these effects, thus, a flexible taper strategy is desirable. Comorbidities, psychological state, functional state, the presence of pain, and anxiety with regards to the taper may fluctuate between patients as well, further enhancing the appeal of a malleable taper strategy. Another consistency was that the length of the taper should reflect the length of the prior opioid therapy. [6,8,9,11,12] This finding was present in several guidelines and was supported by several of the experimental studies. The literature also leaned toward switching the patients onto opioids with long half-lives on a fixed schedule. [9,10,13,14] Another commonality was the recommendation to slow the taper near its end. [9,10,13,15,20,22] Both guidelines and experimental studies supported this advice. However, the exact point that this deceleration should occur was disputed. The suggestion to refer addicted patients or those with complex pain and comorbidities to the indicated specialist was also consistent between guidelines. [8,10,17,18,20] The consensus with addicted patients was that the tapering regimen should be stopped and that the patient should be referred for detoxification treatment. In the guidelines that mentioned pharmacologic adjuvants, clonidine was the most commonly suggested medication. [9,11,16] This finding could be due to clonidine's ability to treat many of the withdrawal symptoms, rather than just one or two.

Limitations
There were several limitations to this review. Generalization of the results in some of the infant and pediatric studies is limited. This impairment stems from concern that withdrawal symptoms in infants and young children differ from those in older children and adults. [21] These two groups of patients also metabolize the medication differently than others. [21] These differences suggest that the findings from these studies may not be applicable to older patients. Another limitation was the lack of comparative and experimental data in the literature.
Much of what is known regarding opioid tapering is based upon guidelines hedged in clinical experience. In fact, many of the guidelines, themselves, either quote previous guidelines or textbooks as sources for tapering information. This practice may have the effect of creating an echo chamber of sorts where information is restated between studies without any experimental or evidence-based developments. Additionally, there is a lack of comparative data regarding the efficacy of taper strategies. Only one study was found in the literature that included adult patients. This study compared the investigator-made taper to the baseline tapering practices of the large tertiary-care center where the intervention was implemented. [12]  Over recent years there has been a surge in opioid use in the United States. A review of medication use in the United States found that hydrocodone with acetaminophen was the most common prescription every year from 2007 to 2011. [28] Of the top 25 most commonly prescribed medications in 2011 three were opioids. [28] Due to this prevalent and escalating use there is a greater need to understand the management of opioid therapy. This comprehension includes tapering. There are several guidelines that present recommendations. These guidelines have considerable variations with respect to rate and duration of the taper. However, they have many similarities. These include the valuing of elements that add flexibility and individualization to the taper. These include the option to hold the taper or to change its rate based upon certain patient factors.

Conclusion
Unfortunately, the literature as a whole is limited. This limitation is due to tapering strategies being founded almost completely on clinical experience. Only one quasi-experimental study has been performed in an adult population. [12] The applicability of a sizable portion of the experimental research is constrained due to its focus on infant and pediatric patients. The downside of these findings is that many of the guidelines cite other guidelines as their source for tapering protocols. The cyclic nature of this practice stagnates progress towards optimizing taper protocols. It also results in greater hardship on the part of the patient. Hopefully more experimental research will be conducted in this area and lead to a standardized protocol. None.
Weaning can be done safely by way of a slower taper. Patients who undergo intensive treatment programs in a pain center or a drug rehabilitation center can be tapered off opioids in 1-2 weeks. Patients being treated in an office-based practice should be tapered more slowly, but the taper should rarely take more than 3 months. A decrease by 10% of the original dose per week is usually well tolerated with minimal physiological effects. Some patients can be tapered more rapidly without problems (over 6-8 weeks). In some patients is may be necessary to slow the taper timeline to monthly, rather than weekly dosage adjustments. A summary of a review by The American Pain Society and the American Academy of Pain Medicine was performed.
Approaches to weaning range from a slow, 10% dose reduction per week to a more rapid 25-50% reduction every few days. Anecdotal clinical experience suggests that at high doses (e.g., over 200 mg/day of morphine or equivalent), the initial wean can be more rapid. The rate of dose reduction often must be slowed when relatively low daily doses, such as 60 to 80 mg daily of morphine (or equivalent), are reached, due to occurrence of more withdrawal symptoms. Patients should be tapered or weaned off chronic opioid therapy when they engage in serious or repeated aberrant drug related behaviors or diversion, experience intolerable adverse effects, or make no progress towards meeting therapeutic goals. When a patient is taking more than 200 mg morphine or its equivalent per day without any significant pain relief, discontinuation of opioid therapy should be considered. Tapering can often be achieved in the outpatient setting in patients without severe medical or psychiatric comorbidities Weekly reduction in dose by 10% is generally well tolerated without symptoms of opioid withdrawal. In more complex cases, detoxification in a rehabilitation setting can be helpful, especially for patients unable to reduce their opioid dose in a less structured setting. If the aberrant behaviors are related to addiction, addiction treatment resources should be made available recommended threshold (these patients should be tapered 10% per week).
If the indication for tapering opioid therapy is due to function and pain not being improved, or if tolerance has developed with long-term opioid prescription, or if comorbidities are present which increase the risk of complication then the patient should be tapered at a rate of 10% every 2-4 weeks. There is a list of behavioral indications for the discontinuation of opioid therapy (these patients should be tapered over 3-7 days, or 15-33% per day). Use of the algorithm decreased taper time by an average of 0.4 days compared to the non-algorithm group. There was also a significant decrease in withdrawal symptoms, and no significant differences in patient self-reports of worst pain or satisfaction with pain management. Opioid-dependent children where enrolled in a prospective, randomized trial of 5versus 10-day opioid weaning using oral methadone. The 5-daywean protocol was defined by a 20% reduction of the initial methadone dose each of 5-days, followed by a 5-day course of placebo. The 10-day wean protocol was defined by a 10% reduction of the initial methadone dose each of 10 days with no placebo course.
Children exposed to opioids for an average of 3 weeks showed no difference in the number of agitation events requiring opioid rescue in either wean group. Most of the events requiring rescue occurred on day 5 and 6 of the wean in both treatment groups. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia.
Pediatrics "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. In one patient, the morphine dose was reduced over 2 weeks to 30mg every 4 hours and then shifted to sustained release morphine (SR) 60g tablets twice daily dose and then reduced further over 2 weeks to 10 mg SR tablets twice daily dose. This schedule was continued for another 2 weeks and then discontinued. The other patient was switched from immediate release morphine to SR morphine tablets 60mg as a twice daily dose and was reduced over 2 weeks to 10mg SR tablets and discontinued after 1 week.
Individual patients may have differing responses to the tapering regimen chosen. Fear or anxiety may be present in the patient regarding the taper.
The last stage of tapering is the most difficult. Researchers for the guideline conducted a systematic review of the literature, focusing on reviews of the effectiveness and safety of opioids in specific populations.
The opioid should be tapered if the patient's pain remains severe despite an adequate trial of opioid therapy. In the elderly, sedation, falls, and overdose can be minimized through lower initial doses, slower titration, benzodiazepine tapering, and careful patient education. For pregnant women taking daily opioid therapy, the opioids should be slowly tapered and discontinued. If this is not possible, they should be tapered to the lowest effective dose. No research-based opioid-tapering guidelines exist in the literature; existing guidelines very widely and are not specific to HCT recipients.
The algorithm addresses a gap in the literature and also provides flexibility when dealing with patient discomfort. Central post-stroke pain is due to neuronal excitability, which is caused by damage to the central nervous system. Anti-epileptic drugs have been suggested as a possible adjunct in the treatment of neuropathic pain. There is conflicting research regarding their efficacy in treating this pain. Further research should be performed in order to determine the efficacy of specific anti-epileptic drugs concerning neuropathic pain, as well as how safe they are in specific populations. An initial improvement of pain was observed. After the dose was increased to 150 mg/day great improvement of both pain and sensory loss was observed within 14 days.
Clinical Drug Investigation