Common Oral Medications that May Need Tapering

Full update August 2021

Tapering to prevent a withdrawal syndrome or disease state worsening is suggested for several medications. The chart below provides suggested tapering strategies for some common oral medications. See footnote a for general considerations.

NOTE: Info may differ from product labeling. Canadian-specific info included if it differs significantly from U.S. labeling.

Drug/Drug Class

Rationale for Taper

Suggested Taper

Antidepressants

Withdrawal symptoms (FINISH syndrome): Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal.16

Symptoms usually begin one to ten days after discontinuation (soonest with paroxetine), and persist for two to three weeks.16

Most common with paroxetine and venlafaxine.3,16

Tapering may not be needed unless the patient has been taking the antidepressant for four to six weeks.16 Canada: taper venlafaxine ER if used for longer than one week.14

Stopping fluoxetine without tapering is often tolerated.16

Consider tapering other antidepressants over at least four weeks, when possible.13 Exceptions include:

  • acute bipolar mania: consider tapering over three to five days.12
  • panic disorder: reduce by one dosage step every one to two months.30
  • obsessive compulsive disorder: reduce by 10% to 25% every one to two months.31

Suggested tapering steps are available at https://www.health.harvard.edu/diseases-and-conditions/how-to-taper-off-your-antidepressant.

If tablet/capsule sizes are limited, use liquid formulations (e.g., citalopram [U.S.], escitalopram [U.S.], paroxetine [U.S.], fluoxetine, sertraline [U.S.]) to achieve smaller doses.16 Compounded liquid formulations may also be available.16

Symptoms that are usually transient and mild.If symptoms are intolerable, increase the dose or switch to fluoxetine, then taper.3,16

See our chart, Choosing and Switching Antidepressants, for tapering information in the context of switching.

Anticonvulsants

Recurrence or worsening of condition being treated or comorbidities (e.g., seizures, mood disorder, headache).5

Gabapentin or pregabalin can cause withdrawal symptoms similar to benzodiazepine or alcohol withdrawal (e.g., anxiety, headache, insomnia).15

Taper gabapentin or pregabalin over at least one week (longer if treating seizures [see below]).15

Other anticonvulsants:

  • seizure disorder: consider a taper of at least three months, when possible.2 Most seizures occur in the first six months after withdrawal, so a slower taper prolongs the “at risk” relapse period.5
  • migraine prophylaxis: consider tapering over two to four weeks.4
  • bipolar disorder: taper over at least two to four weeks.12

Antipsychotics

Recurrence of neuropsychiatric symptoms.13

Withdrawal symptoms reflect the receptor activity of the drug:

  • cholinergic
  • dopaminergic
  • serotoninergic
  • histaminergic
  • adrenergic

Symptoms include movement disorders, somatic symptoms (e.g., flu-like symptoms, paresthesias, tachycardia), and psychological symptoms (e.g., psychosis, confusion).6

Conservative approach: reduce the dose by 25% to 50% every three to six months. A 10% reduction every month could also be tried. Liquid formulations may be needed to achieve small doses.6

If switching to a different antipsychotic, suggested approaches include:7

  • Crossover strategies over several weeks (usually preferred).Examples:
    • ascending taper (i.e., up titrate new agent, then stop old agent [with or without plateau])7
      descending taper (i.e., start new agent at therapeutic dose and taper old agent [with or without plateau])7
      cross-taper (i.e., up titrate new agent to therapeutic dose, then taper old agent [with or without plateau])7
      plateau (i.e., abrupt initiation of new agent, plateau, then abrupt discontinuation of old agent)7
  • Abrupt switch (consider if both agents have long half-lives, or if the patient might have problems with a complex dosing regimen).7

Product labeling for some antipsychotics, particularly long-acting injectable formulations, provide switching guidance.

Baclofen

Worsening of spasticity, or withdrawal symptoms: delirium, hallucinations, confusion, seizures, movement disorders, psychosis, paranoia, mania, anxiety, tachycardia, sweating, insomnia.8

Taper over about one to two weeks.8

Benzodiazepines

See our toolbox, Appropriate Use of Oral Benzodiazepines. The benzodiazepine receptor agonists or “Z drugs” (e.g., eszopiclone, zolpidem, zaleplon, zopiclone) are also included.

Beta-blockers

Sudden withdrawal has been associated with angina, myocardial infarction, and arrhythmias in patients with coronary artery disease.10

In patients without coronary artery disease, only mild, short-lived withdrawal symptoms such as anxiety or tachycardia may be seen, but angina and myocardial infarction have been reported.11

Hypertensive urgency has been reported.9

Taper over one to two weeks.For post-MI patients, consider tapering over as long as three weeks, and having sublingual nitroglycerin available.17 If withdrawal symptoms occur, restart therapy, at least temporarily.10

It is prudent to taper beta-blockers over about a week even in patients without overt coronary artery disease.10

Butalbital combination products
(e.g., Fiorinal)

Headache exacerbation, tremors, delirium, seizures.18

Risk factors: continuous, long-term use of seven or more doses daily.18

Taper by one dose/day, per week (e.g., four tablets per day the first week, three tablets per day the second week, etc).19

If patient taking ≥12 doses daily, consider referral to specialist.18

Calcium channel blockers

Exacerbation of angina.20

No specific taper suggested.

Carisoprodol

Body aches, sweating, palpitations, sadness, anxiety, restlessness, insomnia.21

Long taper (for patients with kidney or liver impairment, age >65 years, or total daily dose >1,400 mg): 350 mg three times daily for three days, then twice daily for three days, then once daily for three days.21

Short taper: 350 mg three times daily for one day, then twice daily for two days, then once daily for one day.21

Cholinesterase inhibitors
(e.g., donepezil)

See our FAQ, Alzheimer’s Dementia Pharmacotherapy.

Clonidine

Withdrawal syndrome: rebound hypertension, headache, restlessness, anxiety, insomnia, sweating, tachycardia, tremor, muscle cramps, hiccups, nausea, salivation; rarely encephalopathy, stroke, death.32

Risk factors: use for more than one month, concomitant beta-blocker use, daily dose >1.2 mg daily, hypertension, cardiovascular disease.32

Taper over one to two weeks (e.g., 0.1 mg every three to seven days).25,34 Beta-blockers increase risk of rebound hypertension during clonidine withdrawal (noncardioselective most problematic [e.g., propranolol]). If patient is also taking a beta-blocker, consider tapering off beta-blocker first. Monitor blood pressure closely after clonidine taper.33

Transdermal: Risk of withdrawal lower than with oral, but consider tapering patches over two to four days or switching to oral clonidine taper.32

Corticosteroids

Adrenal insufficiency or worsening of underlying condition.22

See our toolbox, Corticosteroids: Selection, Tapering, and More.

Guanfacine

Catecholamine rebound: anxiety, nervousness, transient increase in blood pressure higher than pretreatment level (less problematic than with clonidine).23

Taper over one to two weeks25 (e.g., 1 mg every three to seven days).24

H2-blockers

Acid rebound.26

Reduce dose by 50% for four to eight weeks, then stop or switch to a lower-potency agent.26

Memantine
(e.g., Namenda)

See our FAQ, Alzheimer’s Dementia Pharmacotherapy.

Nitrates

Rebound angina.32

Not usually tapered, but consider tapering over one to two weeks with sublingual nitroglycerin as needed.32

Opioids

See our FAQ, Opioid Tapering: Tips for Success.

Parkinson’s disease medications (dopaminergic drugs)

Dopamine agonist withdrawal syndrome (DAWS) (e.g., agitation, anxiety, panic attacks, insomnia, depression, irritability, sweating, nausea, vomiting, generalized pain). Risk factors may include high dose, long duration, impulse control disorder, and deep brain stimulation.29

Levodopa: withdrawal syndrome resembling neuroleptic malignant syndrome.24

Dopamine agonists: may take only days to weeks for some patients, but months to years for other patients. If intolerable withdrawal symptoms occur, increase the dose or restart. Some patients may require continued use at a low dose indefinitely.29

Levodopa: Taper over about four weeks.26

Proton pump inhibitors

See our FAQ, Proton Pump Inhibitors: Appropriate Use and Safety Concerns.

Tapentadol (Nucynta [U.S.], Nucynta IR [Canada], Nucynta ER [U.S.], Nucynta CR [Canada])

Withdrawal symptoms: anxiety, insomnia, dilated pupils, myalgia, gastrointestinal symptoms, runny nose, lacrimation, sweating, psychological symptoms, increased blood pressure, heart rate, or respiratory rate.28

Reduce dose by 10% to 25% every two to four weeks.28

Also see our FAQ, Opioid Tapering: Tips for Success.

Tizanidine (e.g., Zanaflex)

Withdrawal symptoms: rebound hypertension, tachycardia, anxiety, tremor, hypertonia.27

Risk factors for withdrawal symptoms: daily dose ≥20 mg, use for ≥9 weeks, concomitant opioid or benzodiazepine use.27

Decrease dose by 2 to 4 mg each day.27 Tapered over one week in clinical trials.27

Tramadol (Ultram, etc).

See our FAQs, Tramadol Safety and Opioid Tapering: Tips for Success.

Z drugs

See the row titled “Benzodiazepines” above.

  1. General considerations:1
  • It has been suggested that medication dose reduction of 25% at weekly or longer intervals, with patient monitoring, is a reasonable approach to tapering in general.
  • For some medications, more than one tapering method has been proposed, and the best approach is unknown.
  • Evidence is mostly anecdotal, and a more cautious approach may be needed in certain patients (e.g., high dose, long treatment duration, severe disease).
  • When considering a timeline for tapering, take into account the patient’s age, comorbidities, concomitant medications, medication half-life, reason for taper (e.g., side effects), and consequences of withdrawal.
  • Educate patients and caregivers for which symptoms they should alert the prescriber or seek emergency treatment. Reassure and offer symptomatic relief for milder symptoms.
  • Cognitive behavioral therapy may be needed in some situations (e.g., benzodiazepine withdrawal).

References

  1. Beier MT, Martin CM. Gradual dose reduction and medication tapering: a clinical perspective. Consult Pharm2007;22:628-44.
  2. Loro FA, Tijeras EG, Brigo F. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database Syst Rev 2020 Jan 23;1(1):CD005003.
  3. Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006;67 (Suppl 4):27-30.
  4. National Health Service. Rotherham Clinical Commissioning Group. Migraine prophylaxis. December 2015. http://www.rotherhamccg.nhs.uk/Downloads/Top%20Tips%20and%20Therapeutic%20Guidelines/MIGRAINE_PROPHYALXIS%20GUIDANCE%20final.pdf. (Accessed July 12, 2021).
  5. Hixson JD. Stopping antiepileptic drugs: when and why? Curr Treat Options Neurol 2010;12:434-42.
  6. Horowitz MA, Jauhar S, Natesan S, et al. A method for tapering antipsychotic treatment that may minimize the risk of relapse. Schizophr Bull 2021;47:1116-29.
  7. Cerovecki A, Musil R, Klimke A, et al. Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practice recommendations. CNS Drugs 2013;27:545-72.
  8. Product information for Mylan-baclofen. Mylan Pharmaceuticals. Etobicoke, ON M8Z 2S6. April 2021.
  9. e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2021. Beta-adrenergic blocking agents [June 2018]. http://www.e-therapeutics.ca. (Accessed July 13, 2021).
  10. Prescribing information for bisoprolol. Alembic Labs. West Caldwell, NJ 07006. November 2020.
  11. Teichert M, de Smet PA, Hofman A, et al. Discontinuation of beta-blockers and the risk of myocardial infarction in the elderly. Drug Saf 2007;30:541-9.
  12. Management of Bipolar Disorder Working Group. VA/DoD clinical practice guideline for management of bipolar disorder in adults. Washington (DC): Department of Veterans Affairs, Department of Defense; May 2010. http://www.healthquality.va.gov/bipolar/bd_306_sum.pdf. (Accessed July 12, 2021).
  13. Hogan DB. Strategies for discontinuing psychotropic medications. Canadian Geriatrics Society. CGS Journal of CME 2014;4(2):14-8. http://canadiangeriatrics.ca/wp-content/uploads/2016/11/CJG-_CME_4-6.pdf. (Accessed July 11, 2021).
  14. Product monograph for Effexor ER. Pfizer Canada. Kirkland, QC H9J 2M5. May 2020.
  15. Clinical Resource, Comparison of Gabapentin and Pregabalin. Pharmacist’s Letter/Prescriber’s Letter. August 2018.
  16. Jha M, Rush AJ, Trivedi MH. When discontinuing SSRI antidepressants is a challenge: management tips. Am J Psychiatry 2018;175:1176-84.
  17. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60:e44-164.
  18. McLean W, Boucher EA, Brennan M, et al. Is there an indication for the use of barbiturate-containing analgesic agents in the treatment of pain? Guidelines for their safe use and withdrawal management. Can J Clin Pharmacol 2000;7:191-7.
  19. Tepper SJ, Tepper DE. Breaking the cycle of medication overuse headache. Cleve Clin J Med 2010;77:236-42.
  20. e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2015. Calcium channel blockers [May 2018]. http://www.e-therapeutics.ca. (Accessed July 12, 2021).
  21. Jordan J, Hamer A, Ketchum KL. Carisoprodol (Soma) and sedative quantities to be restricted on November 15, 2002. Oregon DUR Board Newsletter 2002;4(8). http://www.orpdl.org/durm/newsletter/articles/volume4/durv4i8.pdf. (Accessed July 12, 2021).
  22. Clinical Resource, Corticosteroids: Selection, Tapering, and More. Pharmacist’s Letter/Prescriber’s Letter. March 2018.
  23. Prescribing information for guanfacine. Unichem Laboratories. East Brunswick, NJ 08816. July 2020.
  24. Clinical Pharmacology powered by Clinical Key. Tampa, FL: Elsevier; 2021. http://www.clinicalkey.com. (Accessed July 13, 2021).
  25. Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007;46:894-921.
  26. Anon. A practical guide to stopping medicines in older people. BPJ 2010;27:10-23. http://www.bpac.org.nz/BPJ/2010/April/docs/bpj_27_stop_guide_pages_10-23.pdf. (Accessed July 13, 2021).
  27. Prescribing information for Zanaflex. Covis Pharma. Zug, 6300 Switzerland. December 2020.
  28. Prescribing information for Nucynta. Collegium Pharmaceutical. Stoughton, MA 02072. March 2021.
  29. Health Canada. Health Product InfoWatch. June 2021. https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/medeffect-canada/health-product-infowatch/june-2021/hpiw-ivps-2021-06-eng.pdf. (Accessed July 26, 2021).
  30. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edition. January 2009. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf. (Accessed July 12, 2021).
  31. American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. July 2007. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd.pdf. (Accessed July 12, 2021).
  32. American Society of Health-System Pharmacists. American Hospital Formulary Service Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 2021.
  33. Anderson JR, Nawarskas JJ. Cardiovascular drug-drug interactions. Cardiol Clin 2001;19:215-34.
  34. Product information for Kapvay. Amdipharm Pharmaceuticals. Dublin 9, IE. February 2020.

Cite this document as follows: Clinical Resource, Common Oral Medications that May Need Tapering. Pharmacist’s Letter/Prescriber’s Letter. August 2021[370817]

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