Fran Lowry

December 12, 2016

BONITA SPRINGS, Florida – Prescribing benzodiazepines pro re nata (PRN), or on an "as-needed" basis, may lead to misuse, new research shows.

Clinicians may erroneously assume that instructing a patient to take the medication as needed will decrease the likelihood that they will take that medication, but it may be having the opposite effect, investigators found.

"More research needs to be done into the prescribing practices of psychiatrists with benzodiazepines, because we found that when we prescribe them as PRN, or as needed, we think that people will take them only when needed, but from our study, it looks as if people are taking them more than we think they should be," lead author Amy Swift, MD, from Mount Sinai Beth Israel, New York City, told Medscape Medical News.

"When they are prescribed as standing, people take them in the expected fashion, but when there is a little bit less standardization of what exactly is expected of the patient, then there is more room for misuse," Dr Swift said.

The study was presented here at the American Academy of Addiction Psychiatry (AAAP) 27th Annual Meeting.

Markers of Misuse

Benzodiazepine prescriptions have been increasing during the past 20 years, not only with respect to the number of people receiving such prescriptions but also in the doses prescribed.

During the same period, adverse events related to benzodiazepines, including overdose deaths, have increased.

"A lot of the focus has been on deaths due to opioid misuse, but research is now showing that many of these people with opioid overdoses have benzodiazepines on board too. So, in order to manage opioid prescriptions, we also have to look at decreasing other risk factors that may be contributing to these dangerous cocktails that cause overdose," Dr Swift said.

"We know more about how benzodiazepines are prescribed in primary care and specialty practices, but little about how they are being prescribed in large psychiatric clinics," she noted. "But studies do agree on a common trend that those receiving benzodiazepines are mostly women between 50 and 60 years old with a diagnosis of anxiety."

In the current study, Dr Swift and colleague Charles Perkel, MD, also from Mount Sinai Beth Israel, collected data for the months of April and May 2015 from their psychiatric outpatient clinic, a training clinic in which third-year residents were the primary prescribers for some 1400 Medicare and Medicaid patients.

The residents and addiction and geriatric fellows in the clinic were asked to look at their caseload and fill out a spreadsheet that included information about who they were prescribing benzodiazepines for, what other medications they were prescribing, what the doses were, and other aspects of their prescribing practices.

The results showed that 241 patients were being prescribed a benzodiazepine by 18 clinicians.

The researchers also tried to identify whether independent variables, such as sex, age, the amount of time during which patients were receiving benzodiazepines, and specific benzodiazepines prescribed, were markers of misuse.

Markers of misuse in patients included their asking for an early renewal of a prescription; violation of I-STOP, the clinic's prescription-drug monitoring program; and patients' conflicts with their healthcare provider.

Most of the patients in the sample were women between the ages of 50 and 60 years who had a diagnosis of major depressive disorder; 71% of these patients were prescribed a benzodiazepine, most commonly, clonazepam (Klonapin, Roche).

"The diagnosis of major depressive disorder was interesting because benzodiazepines are not FDA approved for use in major depressive disorder," Dr Swift noted.

"The average daily benzodiazepine dose was equivalent to about 2.8 mg/day of Ativan (lorazepam, Valeant), but 11% of the patients were getting what the literature has deemed a high dose, which is 6 mg/day of Ativan or more," she said.

Long-term Use Common

The majority of the patients in the sample (60%) had been receiving benzodiazepines for 5 years or longer.

"This is really interesting, because most of the indications for benzodiazepines in the literature call for short-term, limited durations of use, because there aren't many illnesses that necessitate long-term use of benzos," Dr Swift said.

The study yielded several statistically significant results (for all, P < .05). The first was that patients who were prescribed benzodiazepines PRN were significantly more likely to show markers of misuse.

About 6% had asked for early prescriptions; for another 6%, violations had occurred in the I-STOP prescription monitoring program; and about 28% had conflicts with their prescriber.

Interestingly, for about 70% of the patients, compliance with their clinic appointments had been good.

Age, sex, and type of benzodiazepine as well as dose were not associated with markers of abuse.

In patients who were receiving as-needed prescriptions, there were significant associations with markers of benzodiazepine misuse, Dr Swift said.

"We theorize that this is because the prescriber is saying to take them only when needed, and the patient may be thinking, 'I can take them as much as I need,' " she added.

The researchers also found that people with a history of substance use had significantly more early-renewal requests and more conflicts with prescribers.

The length of time on benzodiazepines was not a marker of misuse, but it correlated with conflict with the prescriber.

"If somebody had been on a benzodiazepine for a very long time, and if the prescriber brought up the possibility of any decrease in dose or any discussion around stopping the drug, the person got very agitated. They had become psychologically and physiologically dependent," Dr Swift said.

"More attention needs to be paid to prescribing habits and the appropriateness of prescriptions within a psychiatric clinic. Oftentimes in a training clinic, it is very hard to make changes to regimens for long-standing patients, but often things do have to be changed, and there really needs to be some clear guidelines around how benzodiazepines should be used," she said.

Underrecognized Problem

Commenting on the findings for Medscape Medical News, Carla Marienfeld, MD, director of Addiction Services, Department of Psychiatry, the University of California, San Diego, noted that the misuse of benzodiazepines and the increased risk for overdose and other problems are "an incredibly important topic, and one that is grossly underrecognized by the public at large, as well as by patients in general.

"Interestingly, in this study, patients who are prescribed benzodiazepines only to be taken when needed had higher markers of misuse. Clinicians may falsely assume that someone prescribed the medication on a scheduled basis would be at higher risk of misuse," she said.

"This study also contributes to our understanding that those with a history of a substance use disorder are at higher risk of misusing substances in their futures. This should be an important consideration for any clinician and any patient considering a prescription for a substance with misuse potential," Dr Marienfeld said.

Dr Swift and Dr Marienfeld report no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 27th Annual Meeting. Abstract B-29, presented December 11, 2016.

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