PRESCRIBING GUIDELINES

How Should Benzodiazepines Be Prescribed?

Most developed countries have issued prescribing guidelines for benzodiazepines. It is important to note that guidelines are completely useless if no-one is adhering to them. 

Ireland was quite advanced in doing so, as in 2002 the Benzodiazepine Committee of the Department of Health recommended that these drugs should not be prescribed for longer than 2–4 weeks, depending on their indication, with slightly longer treatment periods permitted for anxiety relief in comparison to insomnia [1]. 

 In the UK, the Committee on Safety of Medicines (1988) recommended that benzodiazepines be used only for the short-term (2 to 4 weeks) relief of “anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness” [2]. They also recommended that short-term use of benzodiazepines is suitable for the short-term relief of severe or disabling insomnia by itself. Subsequently, they applied the same guideline for the non-benzodiazepine drug zopiclone, which is also used to treat insomnia. 

Very similar guidelines have been issued in Denmark and Norway [3].

Similarly, in the USA, the American Psychiatric Association Task Force on Benzodiazepine Dependency drew up a set of guidelines that urged physicians to always endeavor to use the lowest possible therapeutic doses of benzodiazepine for the briefest possible time and to only allow for long-term maintenance of patients on benzodiazepines in rare cases where benefits outweigh the risks [4]. Typically these would include patients with very persistent severe dysphoria or anxiety secondary to another medical condition, and patients with chronic panic disorder or agoraphobia for which benzodiazepines are deemed to be drugs of choice [5]. 

Pennsylvania and New York have recently released prescribing guidelines emphasizing only prescribing two weeks, their dangers and not utilizing cold turkey as a cessation method. 

In Australia & New Zealand, the guidelines specify that benzodiazepines should be used short-term as part of a broader treatment plan and at minimal effective doses [6]. In addition, the Royal Australian College of General Practitioners (RACGP) [7] recommends that patients being prescribed benzodiazepines are recommended to obtain all such prescriptions from the same doctor, so that the prescriber may monitor their risk of dependence [7]. Moreover, the RACGP also issues guidelines for withdrawal as well as for the prescription of these drugs, advocating switching of patients to longer-acting agents prior to the commencement of tapering and highlighting the need for patient cooperation and informed consent. 

 

For New Patients (those not yet dependent):

Every drug approved by the FDA in the US comes with a Prescribing Information pamphlet. 

For example, under ‘Approved Uses'[*] Ativan’s Prescribing Information states,

Ativan (lorazepam) is useful for short-term [emphasis added] relief of manifestations of excessive anxiety in patients with anxiety neurosis. It is also useful as an adjunct for the relief of excessive anxiety that might be present prior to surgical interventions. Anxiety and tension associated with the stresses of everyday life usually do not require treatment with anxiolytic drugs.

Despite only being approved for these uses, Ativan (and other benzodiazepines) are often prescribed off-label (the prescription of a drug for a condition other than that for which it has been officially approved) for a laundry list of non-approved conditions.

[*]It is important to note that the trials performed to approve Ativan (and most other benzodiazepines) for their indicated uses (and to document any risks of the drugs) usually only persist for about 6-10 weeks or so in duration. Clinical trials for Ambien were only 4-5 weeks.

Ativan’s Prescribing Information pamphlet goes on to state,

The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence. The risk of dependence increases with higher doses and longer term use…The dependence potential is reduced when lorazepam is used at the appropriate dose for short-term treatment. In general, benzodiazepines should be prescribed for short periods only (e.g., 2-4 weeks). Continuous long-term use of lorazepam is not recommended [emphasis added].

Ativan has the strongest and most clear warnings of all the benzodiazepines about it being recommended for short-term use only. The FDA petition filed in 2010 sought to have this warning applied to the Prescribing Information for all FDA-approved benzodiazepines. It was ultimately denied.

Similarly, aside from the fact that Klonopin has different approved uses (e.g., panic disorder, seizure disorders) than Ativan, the FDA Prescribing Information for Klonopin states,

The effectiveness of Klonopin in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials [emphasis added]…There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it [emphasis added}…Therefore, the physician who elects to use Klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

The FDA’s Prescribing Information for Xanax states,

Even after relatively short term use at the doses recommended for the treatment of transient anxiety and anxiety disorder (ie, 0.75 to 4.0 mg per day), there is some risk of dependence. Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg/day and for long periods (more than 12 weeks).

The Z-drugs also come with similar warnings about prescribing. For example, Ambien’s Prescribing Information states:

Ambien (zolpidem tartrate) is indicated for the short-term treatment [emphasis added] of insomnia characterized by difficulties with sleep initiation… 

To find FDA Prescribing Information for your specific benzodiazepine or Z-drug, google “[Drug Name] Prescribing Information”.  

In summary, the prescribing guidelines and warnings that these drugs are only intended for short-term use exist and are in place, but they do no good if they go ignored by prescribers and if prescribers do not explain fully in layman’s terms to their patients that taking them long-term puts them at risk for physical dependence and possibly severe withdrawal syndromes.

In those patients that are already dependent:

In those already made iatrogenically dependent (either voluntarily with informed consent or without having been given informed consent) on benzodiazepines and/or Z-drugs, the FDA Prescribing Guidelines for all of the benzodiazepines and Z-drugs warn that they can cause withdrawal and should not be abruptly discontinued, but rather tapered slowly.

The definitions of ‘slowly’, however, vary significantly depending on if you’re reading FDA recommendations (based on trials of a few weeks) or if you’re reading expert recommendations (based on long-term, in-the-field firsthand experiences treating iatrogenically-dependent benzodiazepine patients). The FDA recommends tapers that are much faster than what experts recommend, and while those faster tapers might be tolerated by some, it is clear that in some they cause extreme withdrawal reactions (sometimes causing seizures, psychosis, suicidality and death) that can persist for many months or years.

It is for this reason that experts like Dr. Heather Ashton and Prof. Malcolm Lader, as well as governing agencies like the British National Formulary, recommend much slower, gradual, patient-controlled tapers. In order to complete these tapers, the patients must have a cooperative prescriber that will prescribe the benzodiazepine and/or Z-drug for as long as needed to complete the taper.

This is made clear by Dr. Heather Ashton in her manual, Benzodiazepines: How They Work and How To Withdraw (aka The Ashton Manual):

Nobody should be forced or persuaded to withdraw against his or her will. In fact, people who are unwillingly pushed into withdrawal often do badly…Your doctor may have views on whether it is appropriate for you to stop your benzodiazepines. In a small number of cases withdrawal may be inadvisable. Some doctors, particularly in the US, believe that long-term benzodiazepines are indicated for some anxiety, panic and phobic disorders and some psychiatric conditions. However, medical opinions differ…Your doctor’s agreement and cooperation is necessary since he/she will be prescribing the medication. Many doctors are uncertain how to manage benzodiazepine withdrawal and hesitate to undertake it. But you can reassure your doctor that you intend to be in charge of your own program and will proceed at whatever pace you find comfortable, although you may value his advice from time to time. It is important for you to be in control of your own schedule. Do not let your doctor impose a deadline. Leave yourself free to ‘proceed as the way openeth’, as the Quakers say.

 

Sources:

  1. Benzodiazepines: Good Practice Guidelines for Clinicians. Available online: http://www.dohc.ie/ publications/benzodiazepines_good_practice_guidelines.html (accessed on 24 June 2013).   
  2. Committee on Safety of Medicines. Benzodiazepines, dependence and withdrawal symptoms. Curr. Probl. 1988, 21, 1–2.   
  3. Jorgensen, V.R. Benzodiazepine and cyclopyrrolone reduction in general practice—does this lead to concomitant change in the use of antipsychotics? A study based on a Danish population.  J. Affect. Disord. 2010, 126, 293–298.   
  4. Salzman, C. The APA Task Force report on benzodiazepine dependence, toxicity, and abuse.  Am. J. Psychiatry 1991, 148, 151.   
  5. Salzman, C.; Fisher, J.; Nobel, K.; Glassman, R.; Wolfson, A.; Kelley, M. Cognitive improvement following benzodiazepine discontinuation in elderly nursing home residents. Int. J. Geriatr. Psychiatry 1992, 7, 89–93.  
  6. Smith, A.J.; Tett, S.E. Interventions to improve benzodiazepine prescribing, lessons from the past 20 years to guide future interventions. BMC Health Serv. Res. 2010, doi:10.1186/14726963-10-321.   
  7. Royal Australian College of General Practitioners. Benzodiazepine Guidelines.