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Absence of evidence that the pro re nata regimen confers benefit: a review of the studies

Yoshida, Kazunaria,b; Suzuki, Takefumia,c; Uchida, Hiroyukia,d; Mimura, Masarua

International Clinical Psychopharmacology: September 2013 - Volume 28 - Issue 5 - p 228–237
doi: 10.1097/YIC.0b013e328362db99
Review Articles

Studies were sought that evaluated the prevalence, effectiveness, and safety of pro re nata (p.r.n.) medications in psychiatric practice for which evidence has been scarce despite their wide application. To this end, a systematic literature search was performed using various search engines (last search: October 2012) with cross-referencing. A total of 34 studies were identified: 16 studies on epidemiological usage, 16 retrospective studies on effectiveness/safety as well as reasons, and only two prospective studies on the effectiveness/safety of p.r.n. medications. All the patients studied were inpatients, and the reasons for p.r.n. were acute behavioral dyscontrol in 29 studies. Psychiatric diagnoses and outcome measures to assess effectiveness/safety varied and were described in 27 and 20 studies, respectively. Medications under study included antipsychotics (mainly chlorpromazine, haloperidol, olanzapine, risperidone, or quetiapine), benzodiazepines (mainly diazepam and lorazepam), and antihistamines (mainly diphenhydramine). Altogether, 17 studies reported that p.r.n. medications were effective in psychiatric inpatients. Those two prospective studies targeted solely a child/adolescent population with small sample sizes. Currently available data are limited in number, quality, and scope; there has been only equivocal evidence to guide the choice of p.r.n. medications for psychiatric patients, hence there is a need for more investigations on this important clinical topic.

aDepartment of Neuropsychiatry, Keio University School of Medicine

bDepartment of Psychiatry, Ohizumi Hospital

cDepartment of Psychiatry, Inokashira Hospital, Tokyo, Japan

dCentre for Addiction and Mental Health, Geriatric Mental Health Program, Toronto, Ontario, Canada

Correspondence to Kazunari Yoshida, MD, Department of Neuropsychiatry, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Tel: +81 3 5363 3829; fax: +81 3 5379 0187; e-mail:

Received February 1, 2013

Accepted May 2, 2013

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins