JAMA: "Complex Persistent Benzodiazepine Dependence—When Benzodiazepine..."

JAMA Psychiatry  https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2792518 

 

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May 18, 2022

 

Complex Persistent Benzodiazepine Dependence—When Benzodiazepine Deprescribing Goes Awry

 

Linda Peng, MD1; Thomas W. Meeks, MD2,3; Christopher K. Blazes, MD2,3

 

Author Affiliations

    1Section of Addiction Medicine, Division of General Internal Medicine and Geriatrics, Department of Medicine, Oregon Health & Science University, Portland

    2Department of Mental Health & Clinical Neurosciences, VA Portland Healthcare System, Portland, Oregon

    3Department of Psychiatry, Oregon Health & Science University, Portland

 

JAMA Psychiatry. 2022;79(7):639-640. doi:10.1001/jamapsychiatry.2022.1150

 

 

Benzodiazepines were discovered serendipitously in the 1950s and later marketed as safer alternatives to barbiturates, leading to increased popularity over subsequent decades. Though touted as safe treatments for anxiety and insomnia, problems with benzodiazepines became more apparent by the 1980s, especially risks of physiological dependence, misuse, and addiction. Although clinicians’ enthusiasm for benzodiazepines has waned, they remain popular medications among patients owing to their rapid symptom relief and reinforcing effects. The opioid crisis has dominated headlines, yet benzodiazepines are an underrecognized and important contributor to the public health crisis of drug overdose deaths.1

 

(Note: I cannot access the full article, but there are some comments, which I will post here.)

 

 

3 Comments for this article:

 

May 18, 2022

 

Timely article.

Neil Haas, MD | UCLA

 

This is a thoughtful article at a time when the use of benzodiazepines have become controversial in some circles. This has led some clinicians to arbitrarily decide to have patients discontinue their medication despite a lack of problems. Frequently these physicians lack an understanding of the difference between addiction and dependence. The idea of CPBD has utility.

 

CONFLICT OF INTEREST: None Reported

 

 

June 21, 2022

 

Complex Persistent Benzodiazepine Dependence: A Distinction without a Difference?

 

Lori Karan, MD | Loma Linda University Addiction Medicine Fellowship

 

While there may be a role for chronic benzodiazepine treatment, it is not clear that the proposed DSM-5 categories distinguishing complex persistent benzodiazepine dependence (CPBzD) from benzodiazepine use disorder (BzUD) ought to be the criteria for this treatment decision1.

 

“Complex persistent benzodiazepine dependence” is reminiscent of “complex persistent opioid dependence” coined by Ballantyne in 2012, and Manhapra in 2020.2,3 Prescribers are now trained to employ benzodiazepines in limited amounts and after other therapeutic options are tried, and on-board. The problem remains for “orphan” patients who were started on these medications and have difficulty tapering or discontinuing them. />

 

The underlying basic science question is whether neuroadaptation and allostasis after long-term benzodiazepine use, in addition to rebound anxiety, makes it difficult for patients to discontinue and remain off benzodiazepines. Additionally, we have few studies about whether chronic treatment with benzodiazepine agonists is clinically helpful to maintain select patients’ functioning and quality of life. Opioids act via different neuroreceptors and pathways than benzodiazepines. We know that treatment with opioid agonists, including methadone and buprenorphine, stabilize individuals, prevent relapse, decrease the risk of overdose, and enable persons to function in society. We have few comparable studies with benzodiazepines.

 

Both patients with CPBzD and BzUD can develop tolerance, physical withdrawal, and in the setting of deprescribing, can experience psychological and functional decline resulting in continued use ‘to feel normal.’ Differentiating between CPBzD and BzUD to avoid stigma may help assuage prescribing physicians and patients who have become iatrogenically dependent upon benzodiazepines, but it does not advance the treatment of those with mental illness and/or substance use disorders (SUD).

 

Analogous to buprenorphine, there is no safer available benzodiazepine partial agonist. Unlike the opioid antagonist, naltrexone, use of flumazenil, a short-acting benzodiazepine antagonist, is limited by the risk of seizures. If craving, compulsive use, loss of control, and use despite adverse consequences persist, then substance use disorders therapies are helpful. All patients taking chronic benzodiazepines will benefit from tools addressing their insomnia and anxiety.

 

Risks of benzodiazepines include cognitive and motor impairment, respiratory depression, seizures, and drug interactions caused by polypharmacy. Benzodiazepine prescriptions may be renewed as harm reduction if the benefits outweigh the anticipated risks, and if more urgent issues take precedence. If benzodiazepine prescriptions are continued, then many patients will benefit from random drug testing, pill counts, prescription drug monitoring, and surveillance for aberrant behavior.

 

 

1 Peng L, Meeks TW, Blazes CK. Complex Persistent Benzodiazepine Dependence-When Benzodiazepine Deprescribing Goes Awry. JAMA Psychiatry. 2022 May 18. E1-E2. doi: 10.1001/jamapsychiatry.2022.1150. Online ahead of print.

 

2 Ballantyne JC, Sullivan MD, Kolodny A. Opioid Dependence vs Addiction: A Distinction Without a Difference? Arch Int Med. 2012:172(17):1342-3. https://dot.org/10.1001/archinternmed.2012.3212.

 

3 Manhapra A, Sullivan MD, Ballantyne JC, MacLean RR, Becker WC. Complex Persistent Opioid Dependence with Long-term Opioids. J Gen Intern Med. 2020. 35 (suppl 3): 964-971.

 

 

Lori D. Karan, MD

Lakai Banks-Dean, MD

Waseem Khader, DO

John McNutt, MD

 

CONFLICT OF INTEREST: None Reported

 

June 21, 2022

 

Difficult benzodiazepine prescribing is a conundrum not a syndrome

 

Edward Silberman, MD | Tufts Medical Center, Tufts University School of Medicine

 

June 13, 2022

 

To the Editor:

Benzodiazepines are effective, safe anxiolytics when prescribed appropriately for anxiety disorder patients, but they are viewed as “addictive” by many psychiatrists because they have a withdrawal syndrome. In their viewpoint Peng et al (1) describe difficulties patients may encounter in discontinuing benzodiazepine treatment and usefully distinguish them from manifestations of a substance use disorder. However, it works against the intentions of the authors to list “intoxication or euphoria” as attributes of benzodiazepines, and to imply that benzodiazepine use disorder (BUD) is a syndrome in which these medications are taken by themselves to produce euphoria. Benzodiazepines have, at most, a weak propensity to reinforce their own administration in either animals or humans (2) and BUD is almost invariably a syndrome of polysubstance abuse in which benzodiazepines are used opportunistically as adjuncts to primary drugs of abuse. (3). Failure to make these distinctions contributes to the stigmatization of patients taking benzodiazepines, against which the authors warn us.

 

We also wish to register concern about lumping under a new name a diverse array of withdrawal difficulties about which we have very little solid knowledge. Among the possible causes of such difficulties are high physiologic sensitivity to benzodiazepines and/or their withdrawal, return of untreated anxiety symptoms, inappropriate withdrawal procedures or indications, misattribution of symptoms, tendency toward somaticizing, inappropriate indications for prescribing, inadequate patient education and support, and lack of concurrent non-pharmacologic treatment. We must also remember that the majority of appropriately treated patients have no more than minor difficulty withdrawing from benzodiazepines (5). The present literature gives us little indication of how many patients fall into each category or what the risk factors might be. Combining them under the name complex prolonged benzodiazepine dependence (CPBD) risks reifying the concept as a unitary disorder stemming from benzodiazepine use, which would likely only intensify the already widely entrenched prejudice against these medications. Indeed, one of us has already been asked by a patient “Have you heard about the new CPBD disorder?” The authors’ call for thoughtful attention to the complex problems of benzodiazepine withdrawal would be more likely to succeed if their diverse nature were not painted over with the broad brush of a name.

 

Edward K. Silberman, MD

Richard Balon, MD

Antonio E. Nardi,

 

 

 

 

References

 

1. Peng L, Meeks T, Blazes C. Complex persistent benzodiazepine dependence – When benzodiazepine deprescribing goes awry. JAMA Psychiatry. 2022 doi:10.1001/jamapsychiatry.2022.1150

2. Woods JH, Katz D, Winger G. Abuse liability of benzodiazepines. Pharmacol Rev. 1987; 39:251-413

3. O’Brien C. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry. 2005; 66(suppl 2):28-33

4. Silberman, EK. Stigmatization of benzodiazepines: Pharmacologic and nonpharmacologic contributions. Psychother Psychosom 2022 doi:10.1159/000525208

 

CONFLICT OF INTEREST: None Reported

Oh my.  Quoting from the second comment:

 

Risks of benzodiazepines include cognitive and motor impairment, respiratory depression, seizures, and drug interactions caused by polypharmacy. Benzodiazepine prescriptions may be renewed as harm reduction if the benefits outweigh the anticipated risks, and if more urgent issues take precedence. If benzodiazepine prescriptions are continued, then many patients will benefit from random drug testing, pill counts, prescription drug monitoring, and surveillance for aberrant behavior.

For interested readers, here’s a link to the full opinion piece:

 

https://benzoreform.org/wp-content/uploads/2022/05/jamapsychiatry_peng_2022_vp_220008_1652305578.43285-1.pdf

Thanks, Libertas. I will have a look at that. Articles that require me to sign up for something are just a "no" for the time-being, but I really appreciate that you're able to share this one with all of us. 

While I'm gratified to know there is acknowledgement of the differences between BUD and CPBD it sickens me to read this after all these years:

"Unfortunately, little empirical guidance exists in the literature for benzodiazepine discontinuation, and research is needed to validate the concept of CPBD"

 

 

On 06/09/2022 at 05:43, [[P...] said:

While I'm gratified to know there is acknowledgement of the differences between BUD and CPBD it sickens me to read this after all these years:

"Unfortunately, little empirical guidance exists in the literature for benzodiazepine discontinuation, and research is needed to validate the concept of CPBD"

I’m diagnosed with CPBD. I don’t really want to be part of research that should have happened a long time ago but grateful for the help and frequent attention and therapies from the team.