Keywords
selective serotonin reuptake inhibitor
antipsychotic
psychostimulant
mood stabilizer
Abstract
In psychopharmacology, “drug holiday” refers to the complete discontinuation or planned reduction of a pharmacological treatment for a predetermined and limited period. The duration may vary from several days to several months, depending on the clinical goal and the patient’s condition, and should always be implemented under medical supervision. The primary aims of this approach include alleviating treatment-related adverse effects and preventing the development of tolerance during long-term use, thereby restoring the drug’s therapeutic efficacy. In chronic and prolonged treatment settings, providing the patient with a temporary “drug-free” period may be preferred to reduce side effects and improve overall quality of life. Current clinical guidelines recommend continuing treatment for a certain period after remission is achieved in psychiatric disorders and emphasize that irregular medication use is a significant risk factor for recurrence and relapse. Therefore, the implementation of a drug holiday should be individualized for each patient, planned collaboratively by the clinician and the patient, and carefully evaluated with regard to the benefit–risk balance, the patient’s clinical history, relapse risk, and response to treatment.
References
Alipour-Kivi, A., Eissazade, N., Shariat, S. V., Salehian, R., Soraya, S., Askari, S., et al. (2024). The effect of drug holidays on sexual dysfunction in men treated with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine: an 8-week open-label randomized clinical trial. BMC Psychiatry, 24(1), 67. https://doi.org/10.1186/s12888-024-05507-7
American Psychiatric Association. (2010). Practice guideline for the treatment of patients with major depressive disorder (3rd ed.). American Journal of Psychiatry, 167(10 Suppl), 1–152.
Baldessarini, R. J., Tondo, L., Faedda, G. L., Suppes, T. R., Floris, G., & Rudas, N. (1996). Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders. Journal of Clinical Psychiatry, 57(10), 441–448. https://doi.org/10.4088/jcp.v57n1001
Gitlin, M., Nuechterlein, K., Subotnik, K. L., Ventura, J., Mintz, J., Fogelson, D. L., & Aravagiri, M. (2001). Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. American Journal of Psychiatry, 158(11), 1835–1842. https://doi.org/10.1176/appi.ajp.158.11.1835
Handelman, K., & Sumiya, F. (2022). Tolerance to stimulant medication for attention deficit hyperactivity disorder: Literature review and case report. Brain Sciences, 12(8), 959. https://doi.org/10.3390/brainsci12080959
Herings, R. M., & Erkens, J. A. (2003). Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Pharmacoepidemiology and Drug Safety, 12(5), 423–424. https://doi.org/10.1002/pds.837
Higgins, A., Nash, M., & Lynch, A. M. (2010). Antidepressant-associated sexual dysfunction: Impact, effects, and treatment. Drug, Healthcare and Patient Safety, 141–150. https://doi.org/10.2147/dhps.s7634
Ibrahim, K., & Donyai, P. (2015). Drug holidays from ADHD medication: International experience over the past four decades. Journal of Attention Disorders, 19(7), 551–568. https://doi.org/10.1177/1087054714548035
Kishi, T., Ikuta, T., Matsui, Y., Inada, K., Matsuda, Y., Mishima, K., & Iwata, N. (2019). Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: A meta-analysis. Psychological Medicine, 49(5), 772–779. https://doi.org/10.1017/s0033291718001393
Klein, R. G., Landa, B., & Mattes, Klein, D.F. (1988). Methylphenidate and growth in hyperactive children: A controlled withdrawal study. Archives of General Psychiatry, 45(12), 1127–1130. https://doi.org/10.1001/archpsyc.1988.01800360075011
Kovich, H., Kim, W., & Quaste, A. M. (2023). Pharmacologic treatment of depression. American Family Physician, 107(2), 173–181.
Kupka, R., Regeer, E., Van Bergen, A., Tondo, L., & Bauer, M. (2024). Lithium-discontinuation-induced treatment refractoriness revisited. International Journal of Bipolar Disorders, 12(1), 17. https://doi.org/10.1186/s40345-024-00339-6
Lalegani, E., Eissazade, N., Shalbafan, M., Salehian, R., Shariat, S. V., Askari, S., Orsolini, L., & Soraya, S. (2023). Safety and efficacy of drug holidays for women with sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine: An open-label randomized clinical trial. Brain Sciences, 13(10), 1397. https://doi.org/10.3390/brainsci13101397
Leucht, S., Tardy, M., Komossa, K., Heres, S., Kissling, W., Salanti, G., & Davis, J. M. (2012). Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: A systematic review and meta-analysis. The Lancet, 379(9831), 2063–2071. https://doi.org/10.1016/s0140-6736(12)60239-6
Lohr, W. D., Wanta, J. W., Baker, M., Grudnikoff, E., Morgan, W., Chhabra, D., et al. (2021). Intentional discontinuation of psychostimulants used to treat ADHD in youth: A review and analysis. Frontiers in Psychiatry, 12, 642798. https://doi.org/10.3389/fpsyt.2021.642798
Lorenz, T., Rullo, J., & Faubion, S. (2016). Antidepressant-induced female sexual dysfunction. Mayo Clinic Proceedings, 91(9), 1280–1286. https://doi.org/10.1016/j.mayocp.2016.04.033
Moncrieff, J., Crellin, N. E., Stansfeld, J., Cooper, R. E., Marston, L., Freemantle, N., et al. (2023). Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): An open, parallel-group, randomised controlled trial. The Lancet Psychiatry, 10(11), 848–859. https://doi.org/10.1016/s2215-0366(23)00258-4
National Institute for Health and Care Excellence (NICE). (2022). Depression in adults: Treatment and management. London: NICE.
Nemeth, A., Arato, M., & Treuer, T. (1996). Treatment of fluvoxamine-induced anorgasmia with a partial drug holiday. American Journal of Psychiatry, 153(10), 1365–1365. https://doi.org/10.1176/ajp.153.10.1365a
Noack, C. H., & Trautner, E. M. (1951). The lithium treatment of maniacal psychosis. Medical Journal of Australia, 2(7), 219–222. https://doi.org/10.5694/j.1326-5377.1951.tb68249.x
Ostuzzi, G., Vita, G., Bertolini, F., Tedeschi, F., De Luca, B., Gastaldon, C., et al. (2022). Continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable: A systematic review and network meta-analysis. The Lancet Psychiatry, 9(8), 614–624. https://doi.org/10.1016/s2215-0366(22)00158-4
Pilhatsch, M., Glenn, T., Rasgon, N., Alda, M., Sagduyu, K., Grof, P., & Bauer, M. (2018). Regularity of self-reported daily dosage of mood stabilizers and antipsychotics in patients with bipolar disorder. International Journal of Bipolar Disorders, 6(1), 10. https://doi.org/10.1186/s40345-018-0118-8
Qureshi, M. M., & Young, A. H. (2021). Hamlet’s augury: How to manage discontinuation of mood stabilizers in bipolar disorder. Therapeutic Advances in Psychopharmacology, 15(11). https://doi.org/10.1177/20451253211000612
Rothschild, A. J. (1995). Selective serotonin reuptake inhibitor-induced sexual dysfunction: Efficacy of a drug holiday. American Journal of Psychiatry, 152(10), 1514–1516. https://doi.org/10.1176/ajp.152.10.1514
Suppes, T., Baldessarini, R. J., Faedda, G. L., & Tohen, M. (1991). Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Archives of General Psychiatry, 48(12), 1082–1088. https://doi.org/10.1001/archpsyc.1991.01810360046007
Taşkan, M., Tufan, A. E., Öztürk, Y., Kesikbaş, B. B., İmrek, Y., Akıncı, B., Koçak, G., et al. (2024). Drug holidays may attenuate beneficial effects of treatment on emotion regulation and recognition among children with ADHD: A single-center, prospective study. Psychiatry and Clinical Psychopharmacology, 34(4), 285–293. https://doi.org/10.5152/pcp.2024.24862
Turan, S., Ermiş, Ç., Pereira-Sanchez, V., Tunctürk, M., & Pekcanlar, A. A. (2021). ADHD and drug holidays: Effects on anthropometric changes during methylpenidate treatment. Psychopharmacology Bulletin, 51(3), 10.
Vinkers, C. H., Kupka, R. W., Penninx, B. W., Ruhé, H. G., Van Gaalen, J. M., Van Haaren, P. C., et al. (2024). Discontinuation of psychotropic medication: A synthesis of evidence across medication classes. Molecular Psychiatry, 29(8), 2575–2586. https://doi.org/10.1038/s41380-024-02445-4
Ward, A., Ishak, K., Proskorovsky, I., & Caro, J. (2006). Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: A retrospective database study. Clinical Therapeutics, 28(11), 1912–1921. https://doi.org/10.1016/j.clinthera.2006.11.002
Waxmonsky, J. G., Pelham, W. E., Campa, A., Waschbusch, D. A., Li, T., Marshall, R., et al. (2020). A randomized controlled trial of interventions for growth suppression in children with attention-deficit/hyperactivity disorder treated with central nervous system stimulants. Journal of the American Academy of Child & Adolescent Psychiatry, 59(12), 1330–1341. https://doi.org/10.1016/j.jaac.2019.08.472
Wunderink, L., Nieboer, R., Wiersma, D., Sytema, S., & Nienhuis, F. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy. Schizophrenia Research, 70(9), 913-920.
Zipursky, R. B., Menezes, N. M., & Streiner, D. L. (2014). Risk of symptom recurrence with medication discontinuation in first-episode psychosis: A systematic review. Schizophrenia Research, 152(2–3), 408–414. https://doi.org/10.1016/j.schres.2013.08.001
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Çukurova Journal of Mental Health