Top 7 Drug Classes to Be Tapered Before Discontinuation

Although drugs are often stopped abruptly when therapy is no longer needed, some drugs should be tapered to prevent physiologic withdrawal syndrome and/or disease recrudescence.

Physiologic withdrawal syndrome occurs when an exogenous drug disrupts a normal physiologic feedback mechanism and is then suddenly discontinued. Examples include downregulation of hormone synthesis (eg, with corticosteroids), upregulation of adrenergic receptors after chronic treatment with alpha- or beta-adrenergic receptor antagonists (eg, atenolol, prazosin, terbutaline), hypergastrinemia after chronic treatment with proton pump inhibitors (PPIs), and desensitization of opioid receptors after chronic treatment with opioid agonists.^1-6 Higher doses and longer treatment durations can result in greater disruption to physiologic feedback mechanisms, potentially increasing the likelihood and severity of withdrawal signs if a drug is suddenly discontinued.^1,3,4

For many conditions (eg, immune-mediated diseases, idiopathic seizure disorders), it can be difficult to determine whether resolution of clinical signs following appropriate treatment signifies complete disease elimination, remission, or suppression of signs.^7,8 If disease recrudescence occurs following abrupt drug withdrawal, regaining control of clinical signs may be difficult; tapering is therefore indicated.

General Tapering Strategies

Tapering protocols include magnitude of recommended drug reduction at each step and length of maintenance of the reduced dose before the next reduction. Dose reductions in dogs and cats can range from 10% to 25%, with the new dose maintained for 1 to 4 weeks. Speed of tapering should be based on interrelated factors involving characteristics of the drug, patient, and disease (see Factors to Consider When Choosing a Taper Protocol).

Following are the top 7 drug classes that may need to be tapered to avoid physiologic withdrawal syndrome and/or disease relapse in dogs and cats, according to the author.

1. Corticosteroids 

Physiologic Withdrawal Syndrome

Corticosteroids that have been administered daily for longer than 2 to 3 weeks at doses higher than a physiologic dose (prednisone or equivalent, >0.25 mg/kg) should be tapered to avoid physiologic withdrawal syndrome.¹ Abrupt withdrawal can precipitate signs of hypoadrenocorticism because exogenous glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, blunting cortisol synthesis. 

Disease Recrudescence

In cases of immune-mediated diseases (serious [eg, immune-mediated hemolytic anemia] and less life-threatening [eg, atopy]) controlled by corticosteroid treatment, abrupt discontinuation of corticosteroids can result in recrudescence.⁷

2. Immunosuppressants Other Than Corticosteroids

Disease Recrudescence

In cases of immune-mediated diseases adequately controlled by immunosuppressants (eg, cyclosporine A, mycophenolate, leflunomide), abrupt discontinuation of drug therapy can result in severe recrudescence. Drugs should be slowly tapered and clinical signs monitored for.⁷

3. Anticonvulsants

Disease Recrudescence

Abrupt discontinuation of anticonvulsants (eg, benzodiazepines, barbiturates, gamma-aminobutyric acid analogues) has been associated with withdrawal syndromes, including status epilepticus in dogs.^6,8-10 A tapering duration <3 months is considered rapid in humans, with greater risk for inducing status epilepticus or cluster seizures.^11-13 Evidence-based tapering recommendations for dogs and cats are not available. Whether abrupt discontinuation of anticonvulsants used for analgesic purposes in dogs or cats can precipitate seizures is unknown.

4. Proton Pump Inhibitors

Physiologic Withdrawal Syndrome

PPIs suppress gastric acid production, resulting in lack of feedback inhibition of gastrin secretion. Resulting hypergastrinemia causes parietal cell hypertrophy and hyperplasia proportional to the duration of PPI treatment.¹⁴ Rebound hyperacidity due to robust parietal cell activity in the absence of PPIs can cause heartburn, dyspepsia, and regurgitation in humans following abrupt discontinuation of PPIs.¹⁵

5. Sympatholytics (Alpha- & Beta-Adrenergic Receptor Antagonists)

Physiologic Withdrawal Syndrome

Abrupt withdrawal of adrenergic receptor antagonists has been associated with a rebound increase in receptor sensitivity with possible effects on end organs (eg, cardiovascular system).² For example, abrupt withdrawal of a beta-adrenergic antagonist (eg, atenolol) could result in rebound tachycardia, and abrupt withdrawal of an alpha-adrenergic antagonist (eg, prazosin) could result in rebound hypertension. This rebound effect can be prevented by gradual withdrawal of the drug.²

6. Opioids

Physiologic Withdrawal Syndrome

Chronic exposure to opioids desensitizes opioid receptors through a series of cellular pathways, eventually leading to physical dependence. Morphine dependence was experimentally produced in dogs via administration of high doses twice daily for 5 to 9 consecutive days.⁵ Little is known about opioid withdrawal in clinical veterinary patients, but a tapering protocol is likely prudent for dogs and cats treated with opioids for >2 weeks (based on data from humans and canine models). Clinical signs of opioid withdrawal in dogs include vomiting, diarrhea, and tremors.⁴

7. Behavior-Modifying Drugs

Physiologic Withdrawal Syndrome

In humans, abrupt discontinuation of selective serotonin reuptake inhibitors, tricyclic antidepressants, and antipsychotics can result in symptoms that include sweating, GI disturbances, agitation, restlessness, sleep disturbances, flu-like symptoms, confusion, seizures, and hallucinations.^16,17 Although less is known about withdrawal in veterinary patients, a tapering protocol is likely prudent. Fluoxetine, however, does not require tapering because of the long elimination half-life (33-64 hours) of the active metabolite norfluoxetine in dogs.¹⁸