Tapering – Guidance & Tools

Clinical Update Dec. 2018

Overview

Over the last 20 years, the liberal prescribing of opioids for chronic pain has created a population of patients who been on long term opioid therapy (LTOT) for several years if not decades.  Many patients are on doses well above the CDC recommended upper limit of 90 Morphine Equivalent Dose (MED) for new starts. Patients, however, may be reluctant to taper, fearing withdrawal and increased pain. Prescribers are also asking whether or not tapering is necessary if the patient is stable and compliant on their current dose.  Yet, overdose rates continue to be high compared to historical standard and it is well established that patients on high doses of opioids are at increased risk for a variety of side effects, serious morbidities, and death.  Quality of life may be adversely affected, despite the fact that the patient perceives benefit in terms of pain relief.  Recent research found no significant difference for pain relief between opioid and non-opioid treatment. (ref. The SPACE Randomized Clinical Trial)

For this legacy patient population, prescribers need to carefully assess the risks versus the benefits of continued opioid therapy.  In some cases, where the risks are minimal and the patient appears to be doing well, continued opioid therapy may be justified.  In many cases though a thorough and systematic risk benefit assessment (RBA) will reveal continued pain and dysfunction that indicate that a taper should be initiated and other non-opioid therapies some be employed, including referral to behavioral health or other specialists.  A Systematic Review of 67 studies suggests that several types of interventions may be effective to reduce or discontinue LTOT and that pain, function, and quality of life may improve with opioid dose reduction, but the evidence is of very low quality (ref. A Systematic Review, by Frank et al 2017).  It’s important to recognize that tapering is an art, not an exact science and the speed and duration of the taper should be tailored to the individual needs of the patient.

Below are some guidelines and tools that will help prescribers assess and weigh risks versus benefits, and decide whether tapering is indicated.  For tapering to be successful, clinicians must  approach the taper as an alliance with the patient with the goal of improving their safety and quality of life.

Contributors

These tools, guidance, and resources for tapering were collected and developed by the Oregon Pain Guidance Clinical Advisory Group, Tapering Workgroup.  The workgroup participants and contributors include:

  • Dr. Jane Ballantyne – University of Washington Dept. of Anesthesia & Pain Medicine
  • Dr. Roger Chou – OHSU Department of Medical Informatics & Clinical Epidemiology and Department of Medicine
  • Dr. Paul Coelho – MD Salem Health
  • Dr. Ruben Halperin – Providence, Dept. of Medical Education and OHSU Affiliate Associate Professor, Dept. of Medicine
  • Dr. Andrew Kolodny – Brandeis
  • Dr. Anna Lembke – Stanford University School of Medicine, Psychiatry and Behavioral Sciences and Addiction Medicine
  • Dr. Jim Shames – Jackson County Health and Human Services
  • Mark Stephens – Change Management Consulting
  • Dr. David Tauben – University of Washington Dept. of Anesthesia & Pain Medicine

Special Credit

  • Tapering Flowchart and Risk Benefit Assessment Criteria – Thanks to Dr. Shames, Dr. Ballantyne, Dr. Lembke, Dr. Coelho, Mr. Stephens.
  • BRAVO – Thanks to Dr. Lembke for her BRAVO framework for approaching and tapering patients to safer doses or off opioids entirely.
  • What is a Safe Dose? – Thanks to Dr. Ballantyne for guidance on dose.
  • Buprenorphine & X-Waivers – Thanks to Dr. Halperin and Dr. Ballantyne for background on buprenorphine and X-Waivers.
  • Example Tapering Case – Thanks to Dr. Halperin for the patient tapering case.
  • Frequently Asked Questions – Thanks to Dr. Halperin.
  • References – Thanks to Dr. Chou, Dr. Lembke, Dr. Coelho.

Risk Benefit Assessment & Flowchart

Assessing the Risks and Benefits

We recommend that all legacy patients have a systematic assessment of the risks and benefits of continued opioid therapy.  In some cases, where the risks are minimal, and the patient appears to be doing well, continued opioid therapy may be justified.  In many cases though a thorough and systematic risk benefit assessment (RBA) will reveal continued pain and dysfunction that indicate that a taper should be initiated, in conjunction with increased use of  non-opioid therapies  and possible referral to behavioral health or other specialists.

The patient should be monitored carefully, with a risk – benefit assessment performed quarterly.  The following is a list of potential benefits and risks:

Benefits of Opioid Therapy

  • Improved quality of life – Check if patient is engaged in more activities, has more social interactions, improved sleep, and improved mood. (Screening tools: PEG, Oswestry)
  • Improved pain relief – Check if patient benefits from significant pain relief and that pain is less likely to interfere with activities. Note – While it is difficult to assess, patients may confuse pain relief with relief of withdrawal symptoms between doses. (Screening tools: pain scores, PEG)

Risks of Opioid Therapy

  • OUD or CPOD – Check if patient meets criteria for a diagnosis of Opioid Use Disorder (OUD) diagnosis or Complex Persistent Opioid Dependence (CPOD). See definitions below.
  • Dose over 90 MED – This factor should prompt consideration of tapering to a lower dose.
  • Addiction and mental health disorders – Past history, family history, and psycho-social stressors are all risk factors predicting a poor response to opioids. (Screening tools: ORT, SOAPP-R, SOAPP-8)
  • Co-morbid conditions – Co-morbid conditions can increase the risks from opioids: respiratory disease (COPD, Sleep Apnea, etc.), abnormalities in the endocrine system (depressed testosterone, hypoxemia), cardiac arrhythmias, obesity, dementia, fibromyalgia, depression, anxiety, substance use disorder, history of drug overdoses.  (Screening tools: PHQ-9, GAD-7, PC-PTSD, STOP-Bang)
  • Opioid adverse effects – Ask about opioid related adverse effects such as: constipation, lethargy, sexual dysfunction, confusion, depression, increased risk for falls and fractures, immune suppression, and respiratory depression. These adverse effects may affect quality of life or present risk for serious medical consequences.
  • Co-prescribed sedative hypnotics. Benzodiazepines, alcohol, carisoprodol and other substances can increase the risks of serious side effects and death when combined with opioids. (Check the PDMP, avoid co-prescribing)
  • Query the Prescription Drug Monitoring Program (PDMP) database – This should be done before a first prescription and prior to all medication refills. This ensures that you know exactly what controlled medications are prescribed to your patient and by whom.
  • Urine Drug Screens – Random urine drug screening should be done at least quarterly. Absence of a prescribed drug, or presence of illicit drugs in a UDS requires a reassessment of patient risk.
  • Check for drug diversion – Pill counts at every visit and episodic “call backs” for a count is a simple way to do this. This should be a policy that applies to all patients.  Be aware that patients may be taking some of their prescriptions but diverting the remainder.
  • Involve family members and collateral contacts – Encourage family members or partners to attend the clinic visits. For ongoing treatment especially involving change in behavior, close family members and partners can help patients stay on track.
  • Create an EMR template with a risk benefit checklist – It is very helpful to have an EMR template that incorporates these risk/benefit factors. Completing the template ensures that a systematic risk benefit assessment has been performed and simultaneously documents the results. This can be set with a quarterly reminder.

Definitions

  • Opioid Use Disorder (OUD) – The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses 11 criteria to diagnose opioid use disorder (OUD) as Mild (2-3 symptoms), Moderate (4-5 symptoms), or Severe (6 or more symptoms). If the patient is diagnosed with OUD, the prescriber must either refer the patient to addiction treatment, or can continue to treat the patient with buprenorphine if they have an X-waiver.
  • Complex Persistent Opioid Dependence (CPOD)
    • Complex:  Dependence is complicated by desire to continue taking opioid for the treatment of pain.  Withdrawal is complicated by anhedonia and hyperalgesia which, unlike classic ‘physical’ symptoms, may not reverse within days.
    • Persistent:  Tapering is poorly tolerated.  Tapering, therefore, may fail, or is highly protracted (takes months or years).
    • What distinguishes CPOD from OUD:
      • No craving
      • No compulsive use
      • No harmful use that is not medically directed (patient takes opioid exactly as prescribed)
      • Social disruption is attributed to pain and not to OUD

Flowchart Description

Systematically Assess Risks & Benefits

Carefully consider all the risks and benefits above and document your findings. Based on this Risk Benefit Assessment (RBA) decide whether the benefits outweigh the risks or vice versa.

Benefits > Risks

If the benefits outweigh the risks, you have determined that the patient has a significant decrease in pain and significant improvement in function, and you are confident that the risks are minimal.

Document the RBA and Monitor Quarterly

It is important that you document your assessment of risks and benefits and your decision to continue opioid treatment.  On a quarterly basis, we recommend that you review the patient’s case and confirm that they continue to benefit from opioid treatment.  We encourage you to also try non-opioid and non-pharmacological treatment.

Risks > Benefits

If the risks outweigh the benefits, you have determined that either the dose and/or the risks indicate that a taper should be initiated.  This may well be against the strong desire of the patient to continue.  We recommend that you follow the BRAVO protocol, which gives guidance on broaching the topic with the patient, checking for addiction, pacing the dose reductions, and other alternative therapies to consider.

Able to taper down until Benefits > Risks

The tapering process is likely to take months and sometimes years.  The BRAVO protocol has detailed guidance on pacing and communication with the patient.  We also include an example of a year-long taper based on an actual patient case.  Also, other risk factors may be mitigated by changes in the patient’s circumstances.

On a quarterly basis, re-assess and document the risks & benefits

Throughout the tapering process, it is very important to monitor the patient’s situation for changes in the risk benefit assessment at least quarterly.  Evidence of diversion, doctor shopping, illicit substances in urine drug screening (UDS), would be cause for an immediate change in opioid prescribing.

Not able to taper down until Benefits > Risks

If the patient is unable to tolerate a taper after several months, we recommend the prescriber carefully consider whether there is sufficient evidence for a diagnosis of mild, moderate, or severe OUD.  If not, we recommend that the prescriber consider a diagnosis of “Complex Persistent Opioid Dependence (CPOD).”  See definitions and comparison of OUD versus CPOD.

Dx = Opioid Use Disorder

If you make the diagnosis of OUD, the patient must be transitioned to an addiction treatment program.  If you have an X-Waiver you can continue to treat the patient with buprenorphine.  Otherwise, they must be treated within a SAMHSA approved Opioid Treatment Program.  If you continue to treat them with buprenorphine, continue to monitor the patient for use of other illicit drugs or diversion.

Dx = Complex Persistent Opioid Dependence (CPOD)

If the patient does not meet the criteria for OUD, yet is unable to taper after repeated attempts over a period of several months, then consider a diagnosis of CPOD (see definition).  With a diagnosis of CPOD, we recommend one of two treatment paths: use of buprenorphine off-label for pain or to continue with the taper at a much slower pace.  In either case, you should continue to monitor the patient for use of other illicit drugs or diversion.

Flowchart for Long-Term Opioid Therapy Management

BRAVO Overview

BRAVO Detailed Guidelines

BRAVO Online CME Course

Dr. Lembke, in conjunction with the Stanford Continuing Medical Education, developed an online CME course on tapering which incorporates the BRAVO protocol. The online CME course is excellent and free! It includes videos of Dr. Lembke explaining the BRAVO principles and approach along with patient scenarios.

First register with the Stanford Continuing Medical Education system, then search for “Tapering Patients Off of Chronic Opioid Therapy” August 2018.

Link to Stanford CME system: https://cme.class.stanford.edu/courses/course-v1:CME+045+2017/info

BRAVO Videos

What is a Safe Dose?

It is widely recognized that prolonged continuous high dose opioid pain treatment is neither effective nor safe for the majority of patients.  Also, adverse outcomes tend to be dose dependent, such as deterioration in analgesia and hormonal, immune, and cognitive changes.  For new starts, the CDC recommends evaluation and re-assessment in all patients >50 MED and to avoid doses >90 MED.  These limits were set based on accumulated population data that suggest little gain and marked dose dependent risks above that dose.  We accept that some patients at higher doses may continue to receive higher doses if they are established on chronic opioid therapy, fully compliant and functioning well, have no other risk factors, and are carefully monitored on a quarterly basis.  However, the 90 MED dose level (as part of a complete clinical picture) remains a trigger for continued vigilance using periodic systematic assessment of benefit versus risk.  The danger of continued high dose usage is not the drug itself, which can be safe and effective in the right hands, but the person who has developed a dependency that has led to high dose usage with multiple risk factors.   For these patients, the aim of treatment is to reach a dose which is safe and effective, either tapering the opioid dose or switching to buprenorphine.  The prescriber needs to take time to discuss his or her reasoning with the patient.  The prescriber’s job is to remain empathetic, yet resolute, and communicate to patients that a careful risk–benefit assessment informed by experience and compassion has led to this treatment plan and that to continue opioids under these circumstances would be to cause the patient further harm.

Buprenorphine

Methadone is a synthetic opioid and buprenorphine is a semi-synthetic opioid derived from thebaine, a constituent of opium.  Both these drugs were developed and used as analgesics before they were adopted for use as maintenance treatment for OUD.  Their relatively long half-life makes them particularly suited to OUD maintenance therapy.  Methadone is a pure opioid agonist suitable for open ended dosing, therefore a useful drug for the treatment of severe pain, particularly at the end of life.  Buprenorphine is a partial agonist and antagonist with a ceiling dose, which limits its analgesic utility to the treatment of mild to moderate pain, or chronic pain.  Buprenorphine’s ceiling dose also makes it one of the safest opioids because respiratory depression is unlikely to occur unless its use is combined with concomitant CNS depressants.  Buprenorphine’s favorable side effect profile is the reason this drug received approval for office-based treatment of opioid use disorder by providers who obtain an x-waiver.  Methadone addiction treatment, on the other hand, can only be provided in a controlled setting by addiction trained providers.  Unfortunately, prescribers must cope with some complicated regulations when they use methadone or buprenorphine for patients to treat pain or OUD. This is a problem when treating “legacy” patients for whom the line between use for pain versus opioid use disorder is often blurred.

In Europe buprenorphine has been used for pain for decades.  In the United States, only the transdermal patch has an FDA indication for pain.  The more common sublingual and buccal formulations are only indicated for treatment of OUD and require an x-waiver.

Many providers have found that buprenorphine is an effective tool to assist with tapering high dose COT patient and for some patients, buprenorphine is an effected analgesic.  Using buprenorphine in the absence of a diagnosis of OUD is considered off-label, and ironically can be prescribed without obtaining an x-waiver. Even so, we strongly recommended that all providers prescribing opioids for chronic pain obtain an X-Waiver, since the training helps in the opioid management of chronic pain and associated use disorders, and the certification protects from regulatory scrutiny when there is ambiguity between pain and OUD.

X-Waiver

Treating OUD used to mean working at an outpatient treatment program to be able to prescribe methadone.  The DATA 2000 act expanded the options for opioid treatment and allowed for treatment in primary care setting. The x-waiver is provided by the DEA to physicians who have completed an 8 hour training or NPs who have completed 24 hours training.  After completing the training, the DEA certificate will show the DEA number with an X in front of it to document certification to treat opioid use disorder. Taking the course and getting an x-waiver gives the primary care physician a valuable tool to recognize, diagnose and treat a commonly encountered chronic condition.

The SAMHSA website has several different courses: https://www.samhsa.gov/medication-assisted-treatment/training-resources/buprenorphine-physician-training

Tapering – Frequently Asked Questions

Ruben Halperin – September 2018

In 2016 the CDC published the Guideline for Prescribing Opioids for Chronic Pain in response to the country’s prescription drug overdose crisis, and Oregon Health Authority published additional state-specific recommendations later that year.  The guideline recommendations revolve around assessing risk and benefit of chronic opioid therapy and there is a clear recommendation to carefully assess risk versus benefit when considering titrating to > 50 mg MED and to avoid doses > 90 mg MED.  To mitigate risk for patient who are on high doses or who have other factors contributing to their risk, a taper down to < 90 mg MED and preferably < 50 mg MED is recommended.

The recommendation to taper patient’s opioid doses have caused a lot of anxiety and some push back among physicians.   It is important to address some of the more common concerns.

Why should I taper a patient’s opioid dose down if they are doing fine on their current dose?

  • The most important question to consider is the risk/benefit calculation of their current opioid dose.  It means getting a clearer sense of benefit and appropriately identifying risk.  Is the patient meeting his or her functional goals?  Is the pain significantly decreased? Have non-pharmacologic treatments been given an adequate trial?
  • If the patient is on > 50 mg MED, there is already an increased risk of accidental overdose of up to 4-fold by some studies.  Is the patient being co-prescribed any medications that increase risk like benzodiazepines, sleep medications, muscle relaxants? Are there any co-morbidities that increase the patient’s risk?  Think of pulmonary or cardiac disease, or conditions like sleep apnea.  Are there any side effects that affect quality of life?
  • if the patient is on > 50 mg MED, they have an increased risk of accidental overdose and the physician should consider prescribing naloxone (Narcan) as long as the patient is in this risk category.

My patient has chronic pain and has not exhibited aberrant behavior. Why should I worry about addiction?

  • Some patients on chronic opioid therapy have an opioid use disorder (OUD) that may become clearer if you try to taper down the dose.  Making a diagnosis of an OUD is valuable to the patient since there are effective treatments for an OUD, like buprenorphine, but the diagnosis needs to be made.   If you are treating a patient with chronic opioid therapy, be clear on the diagnosis.
  • Some chronic opioid patients develop hyperalgesia which means the opioid actually contributes to causing the pain.  Whereas the patient feels like they need more pain medication, the treatment is tapering the dose down, or off.

If I start tapering my patient, won’t they just buy pills on the street or turn to heroin?

  • Turning to street drugs, or obtaining prescriptions illicitly is consistent with opioid use disorder.  Remember the 4 C’s:  Control, compulsion, cravings and consequences.  If you are offering your patients appropriate treatment alternatives for their pain, and they are only focused on getting opioids, you may have unmasked an OUD and now have a basis for treating that condition.

My patient says nothing else works for their pain. How can I not give them opioids?

  • It’s important to assess what treatments the patient has tried and what other conditions are contributing to their pain experience.  Are there untreated or undertreated behavioral health issues like depression or anxiety?   Has the patient been screened for sleep conditions that are preventing good quality sleep?  If the patient states they have had physical therapy, assess how much and what kind they have had.  Frequently patients are unaware of the treatment options and haven’t been exposed to a multi-disciplinary approach to treatment.
  • Make it clear to the patient that opioids have not been shown to be effective treatment for chronic pain and that there are other treatments that have been shown to be more effective.  Tapering down the opioid dose or not prescribing opioids doesn’t mean you aren’t taking care of the patient.

Buprenorphine sounds helpful, but why should I get an X-waiver? Won’t my practice just fill up with addicts?

  • Being able to identify and treat OUD is a great benefit to a primary care physician.  Because of the way opioids have been prescribed over the last several decades, most primary care physicians have patients on high dose opioids in their practice.  Some of those will have opioid use disorder.  Some of your patients will be agreeable to tapering, but won’t be able to do so because of withdrawal symptoms.  This inability to come off opioids, even when that is desired by the patient may be indicative of an opioid disorder.

Benzodiazepine Taper/Discontinuation

Benzodiazepines are potentially addictive drugs that may produce physical dependence, amnesia, emotional blunting, psychomotor retardation, and synergistic respiratory depression when combined with opioids. Anxiety, although initially ameliorated by benzodiazepines taken short term, often returns to near baseline levels with chronic use. Patients may be reluctant to taper off of these medications fearing the exacerbation of anxiety that usually accompanies the dose-reduction process.

Unlike opioids, abrupt withdrawal from high doses of benzodiazepines can result in seizures and death. The detoxification resembles alcohol withdrawal in terms of symptomatology and risk. Some patients will need medically supervised residential treatment to successfully discontinue benzodiazepines.

Withdrawal: The longer the treatment, the higher the dosage, the shorter the half-life, or the faster the taper, then the more likely the patient will have withdrawal symptoms. Even small doses of benzodiazepines taken chronically may produce uncomfortable symptoms if discontinued abruptly.

Common Benzodiazepine Withdrawal Symptoms

Difficulty Concentrating Restlessness Agitation Tremor
Increased Acuity to Stimuli Loss of Appetite Diaphoresis Anxiety
Faintness/Dizziness Fatigue/Lethargy Tinnitus Nausea
Muscle Cramps/Twitches Poor Coordination Insomnia Paresthesia
Perceptual Distortions Depersonalization Confusion

 

General considerations

  • Some short-term increase in anxiety is to be expected during the tapering process. This is usually transient, and after achieving a reduced baseline dose, the patient is likely to experience decreased medication-related side effects without an increase in anxiety. Many times, benzodiazepines may be completely discontinued with no increase in symptoms but with improved function and quality of life.
  • The slower the taper, the less the short-term discomfort. Educating the patient about the risks of their current regimen and what to expect as they taper off the medications is often/can be helpful.
  • Some highly motivated patients prefer a rapid taper (weeks versus months). Patient preference needs to be considered in designing a tapering schedule.
  • Psychosocial support is an essential component of successful medication withdrawal for patients who have been on long-term benzodiazepine therapy. Discussions about weaning are often associated with fear and anxiety about the recurrence or worsening of anxiety and/or the development of other withdrawal symptoms. Reassure each patient that supportive adjunctive treatment of withdrawal will be provided as needed, and may be quite helpful, but set expectations that this will not include dangerous replacement medications. Certain non-habit forming medications that treat insomnia specifically (such as trazodone or hydroxyzine) might be useful.
  • Patient empowerment is key to success. Involve patients in the planning from the beginning. Elicit suggestions for healthful activities that can replace reliance on medications.
  • Certain therapies, CBT and trauma-focused care, for example, can be quite helpful in supporting patients through the tapering process and beyond.
  • The last part of the dosage reduction is the most difficult for patients. This is a phenomenon that is true for many psychoactive drugs. You and your patients should anticipate this and use supports that are meaningful to your patients. Even in motivated patients, a slow-down of the tapering process may be necessary toward the end. Liquid forms of medication can be helpful for more precise dosing and can be obtained from a compounding pharmacy.

Discontinuation strategies

Here are two strategies that can be used to taper off of benzodiazepines:

  1. Switching to a long-acting benzodiazepine (or to phenobarbital) and then start slower taper.
  2. Simultaneous treatment with an anti-epileptic drug during taper (allows for a more rapid taper).

Special circumstances

Consider inpatient/medical residential treatment in patients with significant substance abuse history, history of benzodiazepine overdose, seizure disorder, or illicit benzodiazepine use. Modified CIWA-b evaluation or MSSA (withdrawal scoring systems) can be used in such circumstances to determine the total 24-hour dose needed to begin the taper and provide safe medical monitoring of the taper process.

Slow-taper method

  1. Calculate the dose equivalence of the current benzodiazepine into clonazepam, diazepam, or phenobarbital long-acting drug: (Benzodiazepine Equivalence Table). Provide behavioral support to the patient during the tapering process above (see General Considerations concerning opioid tapering).
  2. Switch the patient from the short-acting drug to the longer-acting drug. Be conservative in estimating the long-acting dose since variation in metabolism may create safety issues. Consider a reduction of 25–50% of the calculated dose for initiation of tapering.
  3. See the patient for a return visit a few days after initiating the taper to be sure your dose equivalency is appropriate.
  4. Reduce the total dose of the long-acting agent by 5–10% per week in divided doses.
  5. Consider slowing the taper to 5% or less per week when the dose has been reduced to 25–50% of the starting dose.
  6. Consider adjunctive agents to help with symptoms: trazodone, buspirone, antidepressants, hydroxyzine, clonidine, neuroleptics, and alpha-blocking agents have all been useful.

Benzodiazepine Equivalency Chart

Drug Action Onset Peak Onset (hrs) Half-life (hrs) Eliminator Dose Equivalent
Long-Acting
Chlordiazepoxide (Librium) Int 2–4 5–30 (parent); 3–100 (metab) Oxidation 10mg
Diazepam (Valium) Rapid 1 20–50 (parent); 3–100 (metab) Oxidation 10mg
Flurazepam (Dalmane) Rapid 0.5–2 47–100 (metab) Oxidation 30mg
Phenobarbital (barbiturate) Slow 0.5–4 53–118 (metab) Oxidation 30mg
Intermediate-Acting
Alprazolam (Xanax) Int 0.7–1.6 6–20 (parent) Oxidation 0.5mg
Clonazepam (Klonopin) Int 1–4 18–39 (parent) Oxidation 0.5mg
Lorazepam (Ativan) Int 1–1.5 10–20 (parent) Conjugation 1mg
Oxazepam (Serax) Slow 2–3 3–21 (parent) Conjugation 15mg
Temazepam (Restoril) Slow 0.75–1.5 10–20 (parent) Conjugation 30mg
Short-Acting
Triazolam (Halcion) Int 0.75–2 1.6–5.5 (parent) Oxidation 0.5mg

 

Onset of Action

Rapid = within 15 min.

Intermediate = 15–30 min.

Slow = 30–60 min.

 

References

 

Not used