Journal of Psychosocial Nursing and Mental Health Services

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Psychopharmacology 

Medication Holidays

Robert H. Howland, MD

Abstract

Medication holiday refers to the deliberate interruption of pharmacotherapy for a defined period and for a specific clinical purpose. This should be distinguished from medication nonadherence. Medication holidays can be used for the assessment of efficacy and tolerability of a drug therapy. They also can be used for a therapeutic benefit, such as alleviating adverse effects. To partially reverse the physiological adaptive effects that result from chronic pharmacological stimulation, medication holidays have been hypothesized to “resensitize” neurons to the acute pharmacological effects of a drug. Potential problems associated with medication holidays include the risk of destabilizing patients, difficulty in distinguishing rebound and discontinuation effects, and increasing the risk of poor medication adherence.

Abstract

Medication holiday refers to the deliberate interruption of pharmacotherapy for a defined period and for a specific clinical purpose. This should be distinguished from medication nonadherence. Medication holidays can be used for the assessment of efficacy and tolerability of a drug therapy. They also can be used for a therapeutic benefit, such as alleviating adverse effects. To partially reverse the physiological adaptive effects that result from chronic pharmacological stimulation, medication holidays have been hypothesized to “resensitize” neurons to the acute pharmacological effects of a drug. Potential problems associated with medication holidays include the risk of destabilizing patients, difficulty in distinguishing rebound and discontinuation effects, and increasing the risk of poor medication adherence.

Dr. Howland is Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, Pennsylvania.

The author discloses that he has no significant financial interests in any product or class of products discussed directly or indirectly in this activity, including research support.

Address correspondence to Robert H. Howland, MD, Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213; e-mail: HowlandRH@upmc.edu.

Most prescribed medications are taken consistently for a long time to achieve and maintain their therapeutic effects. Intermittent or poor adherence to taking medication is a common and important clinical problem (Howland, 2007). The phrase medication holiday refers to the deliberate interruption of pharmacotherapy for a defined period and for a specific clinical purpose, and this should be distinguished from medication non-adherence. In this article, I describe reasons for using medication holidays and the potential problems associated with this practice.

Use of Medication Holidays for Therapeutic Assessment

When patients take medication for a long time, patients and clinicians sometimes lose perspective on whether or how well the medication is helping. In addition, patients may have or develop physical symptoms that are perceived as side effects. Questions about medication effectiveness or tolerability are common reasons that clinicians or patients seek a second opinion or that patients decide to change treatment providers. One approach to determine whether a medication is effective or may be causing side effects is to plan a medication holiday while carefully assessing the patient.

Before prematurely deciding to change the treatment, a medication holiday assessment may be most appropriate for patients who have seemingly been stable for a long time, but where there are valid concerns about efficacy or tolerability. Being able to closely monitor such a patient before, during, and after a medication holiday is important. For medicated patients who are hospitalized because of an acute deterioration, an initial medication holiday assessment can help ascertain the relative benefits of the current treatment and whether changing or adding medication might be most appropriate. Obviously, pressure to rapidly stabilize and discharge patients may limit or preclude this kind of assessment.

Use of Medication Holidays for Therapeutic Benefit

Another reason for planning medication holidays is to achieve a therapeutic benefit. This is typically done to alleviate adverse effects but sometimes is used to enhance long-term medication effectiveness in the treatment of Parkinson’s disease (Corona, Rivera, Otero, & Stopp, 1995). The best example of this practice in psychiatry is with the use of central nervous system (CNS) stimulant medications, such as amphetamine and methylphenidate drugs, for attention-deficit/hyperactivity disorder (ADHD). One concern with the use of CNS stimulants in children and adolescents is appetite suppression and sleep disturbances. Planned medication holidays for short (weekends) or longer periods (summer breaks) have been used for this purpose with demonstrated benefits (Martins et al., 2004).

Other examples of medication holidays for therapeutic benefit have been with antidepressant medications (to temporarily alleviate adverse sexual effects) (Rothschild, 1995), antipsychotic medications (to lessen or prevent tardive dyskinesia) (Newton et al., 1989), and to ameliorate the adverse effects of dopamine drugs in Parkinson’s disease (e.g., dyskinesias) (Friedman, 1985). The periodic use of medication holidays to reduce adverse effects, enhance long-term treatment adherence, and reduce antipsychotic medication costs in schizophrenia has been advocated, but this is based on work conducted in the 1960s and 1970s using older generation drugs (Prien, Gillis, & Caffey, 1973; Sharer & Petit, 1981). No contemporary studies have been conducted to further investigate these concepts.

Medication Holidays and Central Nervous System Resensitization

With the long-term use of medications, chronic pharmacological stimulation results in adaptive physiological changes in neurons and neuronal networks in the CNS. Such adaptive changes likely explain the delayed therapeutic effects of most (although not all) medications. Similarly, adaptive changes may account for the eventual development of tolerance to many early-onset, drug-related side effects. Adaptive changes also may explain certain long-term drug-exposure adverse effects, such as tardive dyskinesia with antipsychotic drugs and motor dyskinesias with levodopa. It is possible, although not demonstrated or proven for many drugs, that adaptive changes over time may contribute to a diminution or loss of therapeutic effects during long-term treatment. To partially reverse the adaptive effects of chronic pharmacological stimulation, medication holidays have been hypothesized to “resensitize” neurons to the acute pharmacological effects of a drug. Preclinical work in animals has demonstrated that such effects can be demonstrated with many drugs. Very few clinical studies have investigated this phenomenon in human beings, and most of this work has focused on CNS stimulant drugs and ADHD, antipsychotic drugs and tardive dyskinesia, and levodopa and Parkinson’s disease (Cleghorn et al., 1983; Friedman, 1985; Martins et al., 2004).

Potential Problems with Medication Holidays

What happens during a medication holiday will depend on a variety of factors, including the pharmacology of the drug, the duration of the holiday, the condition being treated, the individual patient, and the patient’s environment.

Some patients are very sensitive to the effects of medication changes, with significantly rapid and profound symptom changes even after a short time without medication (Gardos, 1974). Other patients may show little or no symptomatic changes, and they can seemingly tolerate going without medication. A problem with using a medication holiday, then, is the risk in some patients of destabilizing their illness, with potential consequent effects on their health and their environment. Other than past medication-free experiences, it is usually not possible to predict what will happen during medication holidays.

Another problem with medication holidays is distinguishing rebound (relapse) effects and discontinuation effects. In this context, I am defining a rebound or relapse effect as the return of symptoms that are being suppressed or treated as an intended effect of the medication, whereas a discontinuation effect is the development of symptoms that are related to the pharmacology of the drug and the consequent effects of stopping it. In some cases, rebound and discontinuation effects may be easy to observe and distinguish, but sometimes these phenomena are related or overlap.

A patient taking a selective serotonin reuptake inhibitor (SSRI) for depression or an anxiety disorder, which is helping but causes adverse sexual effects, might benefit from periodic medication holidays for the purposes of sexual activity. Some patients treated with antidepressant drugs will show a rapid return of depression or anxiety symptoms after a short time off medication (a rebound or relapse effect), but other patients may remain asymptomatic for longer periods off medication. Abruptly stopping SSRI drugs is sometimes associated with a distinct discontinuation syndrome characterized by dizziness, weakness, nausea, headache, lethargy, insomnia, anxiety, poor concentration, and paresthesias (unusual tactile sensations) (Balon, 1996). Similarly, stopping antipsychotic drugs during medication holidays, which might be done to manage adverse sexual effects or minimize or prevent tardive dyskinesia, can be associated with rebound psychosis or discontinuation dyskinesias (Weinberger, Bigelow, Klein, & Wyatt, 1981). Assessing the relative effects and benefits of a medication holiday is not always unambiguous. In clinical practice, gradual dosage reductions are used to avoid various medication-related rebound and discontinuation effects, but this strategy obviously would counter what is intended with planned short-term medication holidays.

If a drug is stopped during a medication holiday, what happens when it is restarted? If there was some apparent loss of therapeutic benefit during the medication holiday, it might be expected that restarting the drug will be associated with some delay in re-equilibrating to its effects. For example, the benefits of a CNS stimulant drug may be more apparent during the middle and latter parts of a school week, but less so for a day or two after a weekend medication holiday. Similarly, resuming a medication at a full dosage after a medication holiday might be associated with acute adverse effects, especially if tolerance to adverse effects had occurred previously after chronic dosing (Meredith, 1996).

A last problem with medication holidays is the message to patients and families that not taking medication may be acceptable. Even if the limited intent of planned medication holidays is clearly articulated, along with a discussion of the potential risks of doing so, patients may begin to question whether taking the medication is even necessary. This is more likely to eventually occur if they feel well or function well without medication for periods of time. Unfortunately, for most chronic disorders patients at risk of relapsing eventually do relapse without maintenance treatment. When this occurs, it is sometimes more difficult to restabilize patients, even by restarting a previously effective medication.

Conclusion

Medication holidays can be used for therapeutic assessment or therapeutic benefit, but they can be associated with various problems. Except for CNS stimulant drugs and ADHD, the relative risk-benefit ratio of medication holidays generally is not favorable for various mental disorders, and this practice should be discouraged. In their direct care role with patients and families, nurses should be aware of the potential benefits and real problems associated with medication holidays. Because nurses would be most likely to monitor patients during medication holidays, they should be especially familiar with potential rebound and discontinuation effects associated with particular medications and conditions.

References

  • Balon, R. (1996). Drug holidays to counter sexual dysfunction. American Journal of Psychiatry, 153, 1370–1371.
  • Cleghorn, J.M., Brown, G.M., Brown, P.J., Kaplan, R.D., Dermer, S.W. & MacCrimmon, D.J. et al. (1983). Growth hormone responses to apomorphine HCl in schizophrenic patients on drug holidays and at relapse. British Journal of Psychiatry, 142, 482–488. doi:10.1192/bjp.142.5.482 [CrossRef]
  • Corona, T., Rivera, C., Otero, E. & Stopp, L. (1995). A longitudinal study of the effects of an L-dopa drug holiday on the course of Parkinson’s disease. Clinical Neuropharmacology, 18, 325–332. doi:10.1097/00002826-199508000-00004 [CrossRef]
  • Friedman, J.H. (1985). “Drug holidays” in the treatment of Parkinson’s disease: A brief review”. Archives of Internal Medicine, 145, 913–915. doi:10.1001/archinte.145.5.913 [CrossRef]
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  • Howland, R.H. (2007). Medication adherence. Journal of Psychosocial Nursing and Mental Health Services, 45(9), 15–19.
  • Martins, S., Tramontina, S., Polanczyk, G., Eizirik, M., Swanson, J.M. & Rohde, L.A. (2004). Weekend holidays during methylphenidate use in ADHD children: A randomized clinical trial. Journal of Child and Adolescent Psychopharmacology, 14, 195–206. doi:10.1089/1044546041649066 [CrossRef]
  • Meredith, P.A. (1996). Therapeutic implications of drug “holidays.”European Heart Journal, 17(Suppl. A), 21–24.
  • Newton, J.E., Cannon, D.J., Couch, L., Fody, E.P., McMillan, D.E. & Metzer, W.S. et al. (1989). Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients. Journal of Clinical Psychiatry, 50, 132–135.
  • Prien, R.F., Gillis, R.D. & Caffey, E.M. Jr.. (1973). Intermittent pharmacotherapy in chronic schizophrenia. Hospital & Community Psychiatry, 24, 317–322.
  • Rothschild, A.J. (1995). Selective serotonin reuptake inhibitor-induced sexual dysfunction: Efficacy of a drug holiday. American Journal of Psychiatry, 152, 1514–1516.
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  • Weinberger, D.R., Bigelow, L.B., Klein, S.T. & Wyatt, R.J. (1981). Drug withdrawal in chronic schizophrenic patients: In search of neuroleptic-induced super-sensitivity psychosis. Journal of Clinical Psychopharmacology, 1, 120–123. doi:10.1097/00004714-198105000-00002 [CrossRef]
Authors

Dr. Howland is Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, Pennsylvania.

The author discloses that he has no significant financial interests in any product or class of products discussed directly or indirectly in this activity, including research support.

Address correspondence to Robert H. Howland, MD, Associate Professor of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213; e-mail: .HowlandRH@upmc.edu

10.3928/02793695-20090804-01

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