Examining the Risks and Benefits Benzodiazepine Landscape in the - - PDF document

Examining the Risks and Benefits from Benzodiazepines

Rakesh Jain, MD, MPH

Clinical Professor Department of Psychiatry Texas Tech Health Sciences Center School of Medicine Midland, Texas Adjunct Clinical Affiliate University of Texas at Austin School of Nursing Austin, Texas

Saundra Jain, MA, PsyD, LPC

Benzodiazepine Landscape in the United States Is Benzodiazepine (and “Z” Sedative Drug) Use

Rare in America?

SSRI = selective serotonin reuptake inhibitor; SARI = serotonin antagonist and reuptake inhibitor; SNRI = serotonin norepinephrine reuptake inhibitor. Brand names are included in this table for participant clarification purposes only. No product promotion should be inferred. Moore TJ, et al. JAMA Intern Med. 2017;177(2):274-275.

Top 10 Prescriptions for Psychotropics Written in America (2013 Medical Expenditure Panel Survey)

Answer – These Agents are Utilized Very Frequently in the United States

Moore TJ, et al. JAMA Intern Med. 2017;177(2):274-275.

In 2013:

• There were 5,259,000 prescriptions for Alprazolam
• There were 4,865,000 prescriptions for Zolpidem
• There were 3,273,000 prescriptions for Clonazepam
• There were 3,165,000 prescriptions for Lorazepam

Who Exactly is Receiving the Anxiolytic/ Sedative/Hypnotic Class of Medications?

Moore TJ, et al. JAMA Intern Med. 2017;177(2):274-275.

US Adult Population Exposed to Psychiatric Drugs (%) All Numbers are high, but highest risk is associated with:

• 1. Female

gender

• 2. Older age
• 3. White race

Is There a Problem with the Use of Benzodiazepines?

BZD Link with Accidental Falls

AD = Alzheimer’s disease; BZD = benzodiazepine; BZDR = BZD and related drug; HR = hazard ratio. Wadsworth EJ, et al. Hum Psychopharmacol. 2005;20(6):391-400. Cumming RG, et al. CNS Drugs. 2003;17(11):825-837. Lader M. Addiction. 2011;106(12):2086-2109. Saarelainen L, et al. J Am Med Dir

• Assoc. 2017;18(1):87.e15-e87.e21.
• In a questionnaire survey
• f

8000 people in 2 districts of Wales, BZD use was associated with injuries outside work and cognitive failures

• The risk of hip fractures

in older adults can be increased by as much as 50%

In a recent Finnish study of patients with

• r without AD, BZDR use was associated

with an increased risk of hip fracture in persons:

• With AD – HR increase is 1.4
• Without AD – HR increase is 1.6

BZD Use and Risk of Hip Fracture

CI = confidence interval. Saarelainen L, et al. J Am Med Dir Assoc. 2017;18(1):87.e15-e87.e21.

Duration

• f Use

in Days Register-based Medication Use and Alzheimer’s disease (MEDALZ) study, including all community-dwelling persons diagnosed with AD in Finland during 2005–2011 (n = 70,718) and their matched comparison persons without AD. BZDR use was associated with an increased risk of hip fracture in persons with and without AD (adjusted HR 1.4 [95% CI 1.2–1.7] and 1.6 [95% CI 1.3–1.9], respectively)

A Publication from VA Clinicians

VA = Veterans Affairs. Paquin AM, et al. Expert Opin Drug Saf. 2014;13(7):919-934.

• BZDs have been linked to falls, fractures, cognitive

decline, amnesia, impaired psychomotor speed (eg, motor vehicle accidents), and nursing home placement

• Such risks above are of greatest concern among older

adults, who are more sensitive to medicines and most vulnerable to their consequences

• The pharmacokinetic and pharmacodynamic changes in

the aging body and brain make older patients vulnerable

• As a result, all BZDs are on the list of Potentially

Inappropriate Medications in the 2012 Beers Criteria

The Ugly Side of BZDs: It Plays an Important Part in Drug Overdose Deaths

Piercefield E, et al. Am J Prev Med. 2010;39(4):357-363.

Oklahoma State Drug Overdoses 1994–2006 A total of 2112 fatal unintentional medication overdoses were identified Crude overdose death rates increased 7-fold during the investigation period in 2006

4.5% 14.7% 15.2% 19.3% 30.9% 0.0% 10.0% 20.0% 30.0% 40.0%

Diazepam Oxycodone Alprazolam Hydrocodone Methadone Individual drugs contributing most frequently

BZD Use and Dementia Risk – Case Control Studies Also Show Heightened Risk

BZDR = BZD and related z-substance; OR = odds ratio. Gomm W, et al. J Alzheimers Dis. 2016;54(2):801-808.

• The regular use of BZDRs was associated with a significant

increased risk of incident dementia for patients aged ≥ 60 years

• Adjusted OR 1.21, 95% CI 1.13–1.29
• The association was slightly stronger for long-acting substances

than for short-acting ones

• A trend for increased risk for dementia with higher exposure was
• bserved

Independent German analysis:

Conclusion: The restricted use of BZDRs may contribute to dementia

prevention in the elderly

The World’s Latest and Largest Meta-Analysis of Dementia Risk with BZDs Reveals...

Islam MM, et al. Neuroepidemiology. 2016;47(3-4):181-191.

Odds of dementia were 78% higher in those who used BZDs compared with those who did not use BZDs (OR 1.78; 95% CI 1.33–2.38) Meta-analysis pooled data from 8 studies. These 8 studies included 66,177 participants and 30,914 cases of dementia

BZD Use and Association with AD – Emerging Data is Concerning

Billioti de Gage S, et al. BMJ. 2014;349:g5205.

• Dose-effect relationship between BZD use and increased

risk of AD in older people treated previously for > 3 months

• Higher risk for long-acting formulations
• Nature of the link cannot be definitively established
• BZD use may be an early marker of a condition

associated with an increased risk of dementia

• Recommend shortest duration and short half-life

formulations

Another Set of Very Large Databases – FDA and Canadian Pharmacovigilance Data Set, Reveals…

Takada M, et al. Int J Med Sci. 2016;13(11):825-834.

US / FDA database revealed BZD use increased OR of dementia risk by 1.63 (n = 1,971,750)

The Famous BMJ Gray Study from 2016

Are the Conclusions Corrrect?

TSSD = total standardized daily doses. Gray SL, et al. BMJ. 2016;352:i90.

• Over a mean follow-up of 7.3 years, 797 participants (23.2%)

developed dementia, of whom 637 developed AD

• For dementia, the adjusted HRs associated with cumulative BZD

use compared with nonuse were 1.25 (95% CI 1.03–1.51) for 1–30 TSDDs; 1.31 (1.00–1.71) for 31–120 TSDDs; and 1.07 (0.82–1.39) for ≥ 121 TSDDs Conclusion: The risk of dementia is slightly higher in people with minimal exposure to BZDs but not with the highest level of exposure. These results do not support a causal association between BZD use and dementia.

“…given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, healthcare providers are still advised to avoid benzodiazepines…”

Does Cognition Improve after Withdrawal from Long-Term BZD Use?

Barker MJ, et al. Arch Clin Neuropsychol. 2004;19(3):437-454.

META-ANALYSIS OF 10 STUDIES

Does cognitive function of long-term BZD users improve post-withdrawal? Are previous long- term BZD users still impaired at 6-month follow-up?

Does Cognition Improve after Withdrawal from Long-Term BZD Use? (cont’d)

Barker MJ, et al. Arch Clin Neuropsychol. 2004;19(3):437-454.

• Improvement in cognitive function does occur following

withdrawal from long-term BZD use

• Patients withdrawn from long-term BZD use continued to

perform more poorly than controls across all cognitive categories, except sensory processing

• As age increased post-withdrawal cognitive recovery

decreased on tasks of attention/concentration

N = 297 N = 284

Overdose Situations with BZDs:

Where Did These Medications Come From?

ED = emergency department. Buykx P, et al. Aust N Z J Public Health. 2010;34(4):401-404.

Interviews were conducted with 31 patients who attended the ED following a medication overdose and typical stories regarding the acquisition of medications reported.

Conclusion: We are the main suppliers of BZDs that are ultimately used in overdoses !

Treatment Purposes, 77%

Recreational Use, 16% Overdose, 7%

Facts: Examining Recent Data

Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. Substance Abuse and Mental Health Services Administration. www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm. Accessed June 5, 2017. Shah NA, et al. Am J Addict. 2012;21 Suppl 1:S27-S34. Jann M, et al. J Pharm Pract. 2014;27(1):5-16.

Total ED Visits – Non-medical use of BZDs Rose 149% from 2004 to 2011. Alprazolam indicated in ~ one-third of visits, and in ~ one-third of BZD-related suicide attempts ED Visits – BZDs + Alcohol BZDs were involved in 123,572 of the 606,653 ED visits in 2011 that involved drugs and alcohol taken together (20.4%) Drug-Related Deaths Alprazolam – 17% of drug-related deaths; at least 1 other drug (typically an opioid) identified in 97.5% of alprazolam cases (West Virginia forensic database). Deaths attributed to BZDs increased 5-fold from 1999 to 2009; Alprazolam second

• nly to oxycodone with the highest increase in death rates

Why are Benzodiazepines Addictive? Understanding the GABAA Receptor and How BZDs Affect It

GABA = gamma-aminobutyric acid. Soyka M. N Engl J Med. 2017;376(12):1147-1157.

The GABAA receptor consists of 5 trans- membrane glycoprotein subunits arranged around the central chloride

• channel. Each subunit is

composed of 4 domains (domains 1 through 4); domain 2 is the part of the monomeric subunit that lines the chloride channel. BZDs increase the affinity

• f the GABAA receptor for

GABA and the likelihood that the receptor will open for chloride ions.

How BZDs Can Become Addicting in Some Patients

Tan KR, et al. Nature. 2010;463(7282):769-774.

 BZDs increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABAA receptors in nearby interneurons  Such disinhibition, which relies on α1-containing GABAARs expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement  Data provide evidence that BZDs share defining pharmacologic features of addictive drugs through cell type-specific expression of α1-containing GABAARs in the ventral tegmental area

 ”…benzodiazepines act through mechanisms similar to those of other drugs of abuse.” - Soyka M. N Engl J Med. 2017;376(12):1147-1157.

Who’s at Risk to Develop BZD Addiction?

Soyka M. N Engl J Med. 2017;376(12):1147-1157. Okumura Y, et al. Drug Alcohol Depend. 2016;158:118-125.

• A special characteristic of BZDs is that physical and

mental dependence can develop in the absence of tolerance

• Clinical correlates of long-term BZD use are:

– Older age (> 65 years), – Prescription by a Psychiatrist – Regular use – Use of a high dose, and – Concomitant prescription of psychotropic drugs

Cycle of BZD Use

Janhsen K, et al. Dtsch Arztebl Int. 2015;112(1-2):1-7. It can be assumed that the majority of consumed BZDs were not obtained on the black market but were prescribed by doctors. The good effectiveness in terms of the target symptoms creates great affinity in patients towards their medication—even before manifest dependency develops. Furthermore, most patients are likely to have gone through a prolonged history of suffering before they were given BZD medication, so they desire rapid intervention and need it too. Patients therefore put pressure on their doctors who prescribe the drug to

• them. Those affected fear

that their initial symptoms might return. In many cases, prescriptions are issued at patients’ explicitly expressed wishes.

“Without any doubt, doctors are crucially involved in the long- term prescribing of benzodiazepines.”

The Advantages and Disadvantages

• f Using BZDs

Are BZDs a Good or a Bad Idea?

Benzos are ALWAYS a good idea and we are way under prescribing it – Benzos are ALWAYS a bad idea and we are way over prescribing it –

When it comes to prescribing BZDs, do you ever feel like this?

It’s Important to Establish a Few Things

• While a few patients develop problems associated

with BZD use, most don’t

• Most

treatment guidelines do recommend the judicious use of BZDs

• The goal of this presentation is not to create “fear

mongering” among us clinicians

• Many patients are on long-term BZD therapy and

don’t have problems associated with them. They should not be unnecessarily taken

• ff

these medications – that can be harmful to their well- being.

Let there be no doubt – decades of experience has taught us that BZDs are often very helpful, many patients benefit preferentially from them, don’t abuse them, and use them safely for prolonged periods of time Therefore, framing any conversation along the lines of “BZDs are good” or “BZDs are bad” is fundamentally flawed Similarly, we cannot ignore the recent data emerging from addiction literature, ED settings, law enforcement,

• verdose databases, neurobiology literature, long-term

epidemiological outcome data, etc.

The Pros and Cons Associated with BZD Use

Möller HJ. J Clin Psychopharmacol. 1999;19(6 Suppl 2):S2-S11.

Pharmacologic Benefits Therapeutic Uses Adverse Experiences Anticonvulsive Cerebral seizures Epilepsy Centrally muscle-relaxing Central spasticity Muscle tension Tetanus Muscle asthenia, ataxia Disturbance of gait Respiratory depression Sedative/hypnotic Sleep disturbances Premedication in anesthesiology Diurnal sedation Reduced attentiveness Amnestic Various applications in anesthesiology Amnesia (anterograde) eg, when used as a hypnotic Anxiolytic, subduing excitement, and aggression Tense, excited, and anxious states of various origins Stress shielding Indifference Retreat from reality Flattening of affect

Low Cost Availability Rapid Relief of Symptoms Effective Therapy for Many Patients

BZDs Have Several Positive Attributes

Potts NL, et al. Can Fam Physician. 1992;38:149-153.

FDA Indications of Select BZDs

GAD = generalized anxiety disorder. US Food and Drug Administration. Drugs@FDA. www.accessdata.fda.gov/scripts/cder/daf/.

Drug FDA Indication

Alprazolam Panic disorder – with or without agoraphobia. GAD Lorazepam Management of anxiety disorders, anxiety symptoms associated with depression Clonazepam Seizures, panic disorder Diazepam Anxiety disorders, alcohol withdrawal, status epilepticus Muscle spams, surgical procedures Temazepam Insomnia Flurazepam Insomnia Triazolam Insomnia

Spectrum of Concerns Associated with Short- and Long-Term BZD Use

Ashton CH. Benzodiazepines: How They Work And How To Withdraw. August 2002. www.benzo.org.uk/manual/bzcha01.htm. Accessed June 5, 2017. Potts NL, et al. Can Fam Physician. 1992;38:149-153.

Over-sedation Drug Interactions Cognitive Difficulties Depression, Emotional Blunting Neurodegeneration Adverse Effects: Elderly Adverse Effects: Pregnancy Drug Abuse/Dependence Socioeconomic Cost: Long-term BZD Use

If You Do Decide to Taper: Some Advice

Titrating Doses Close Observation & Follow-up Proper Screening Patient Education

Safety Measures When Using BZDs

Potts NL, et al. Can Fam Physician. 1992;38:149-153.

Getting to Better Know Our Common BZDs Kinetics

Soyka M. N Engl J Med. 2017;376(12):1147-1157.

Today, approximately 35 benzodiazepine derivatives exist

BZD Taper and Withdrawal: Specific Suggestions

Soyka M. N Engl J Med. 2017;376(12):1147-1157.

• Recommendations range from reducing the initial BZD

dose by 50% every week or so, to reducing the daily dose by between 10% and 25% every 2 weeks

• A period of 4-to-6 or 4-to-8 weeks is suitable for withdrawal

for most patients

• If possible, prolonged reductions over a period of many

months should be avoided in order to prevent the withdrawal treatment from becoming the patient’s “morbid focus”

When Not to Consider Taper or Withdrawal of BZDs

Soyka M. N Engl J Med. 2017;376(12):1147-1157.

• Those with a severe depressive episode or other major

mental disorder who need BZDs for stabilization

• Some elderly patients – as withdrawal can be difficult to

achieve in some elderly persons with long-term, low- dose dependence on hypnotic agents

• For patients without any motivation for withdrawal
• If complete discontinuation of BZDs is unlikely, one can

attempt to reduce the dose as a harm-reduction strategy

Recognizing the Trifecta Cluster of Signs and Symptoms of BZD Withdrawal

Soyka M. N Engl J Med. 2017;376(12):1147-1157.

Vegetative Symptoms Psychopathologic Symptoms Neurologic and Physical Complications

What Does BZD Withdrawal Look Like?

Non-specific Symptoms Frequency (%) Insomnia 71 Anxiety 56 Mood swings 49 Myalgia/muscle twitching 49 Tremor 38 Headache 38 Nausea/vomiting/loss of appetite 36 Sweating 22 Blurred vision 20 Other Feelings of unreality 24 Complications Psychosis 7 Epileptic seizures 4 Janhsen K, et al. Dtsch Arztebl Int. 2015;112(1-2):1-7. Sensory Disturbances Frequency (%) Hypersensitivity to

• Noise

38

• Light

24

• Smells

15

• Touch

7 Hyposensitivity to

• Smells

15

• Taste

4 Qualitative changes

• Movement

> 24

• Vision

> 13

• Taste

13

• Hearing

2

• Smells

2

Differential Diagnosis of BZD Withdrawal

Soyka M. N Engl J Med. 2017;376(12):1147-1157.

Take-home message: Don’t always assume that the patient is experiencing BZD withdrawal without engaging in a differential diagnosis process!

Create a Checklist – A “Framework” before Beginning Taper

Paquin AM, et al. Expert Opin Drug Saf. 2014;13(7):919-934.

• Safely stopping BZDs

among older, chronic users is feasible and frequently successful

• Importantly, these

authors did not find evidence suggestive of severe withdrawal symptoms or safety concerns, even with high BZD dose and long duration of use

Results of Analysis to See if Dose and Duration of BZD Use Would Impact Elderly Taper Success

Paquin AM, et al. Expert Opin Drug Saf. 2014;13(7):919-934.

Goals for Offering Psychotherapeutic Interventions in BZD Dependence

Soyka M. N Engl J Med. 2017;376(12):1147-1157. Lader M, et al. CNS Drugs. 2009;23(1):19-34.

Psychotherapeutic interventions for long-term BZD use have 3 goals:

• 1. Facilitate the withdrawal itself
• 2. Facilitate further abstinence
• 3. Treat the underlying disorder

BZD Withdrawal Guidelines: UK Guidelines on Clinical Management

Loprazolam and nitrazepam are investigational drugs. Department of Health (England) and the Devolved Administrations. Drug Misuse and Dependence: UK Guidelines on Clinical Management. 2007. www.nta.nhs.uk/uploads/clinical_guidelines_2007.pdf. Accessed June 5, 2017.

Approximate dosages of common benzodiazepines and z-drugs equivalent to 5 mg of diazepam Drug Dose Chlordiazepoxide 15 mg Diazepam 5 mg Loprazolam 500 µg Lorazepam 500 µg Nitrazepam 5 mg Oxazepam 15 mg Temazepam 10 mg Zaleplon 10 mg Zopiclone 7.5 mg Zolpidem 10 mg Drug Dose Chlordiazepoxide 15 mg Diazepam 5 mg Loprazolam 500 µg Lorazepam 500 µg Nitrazepam 5 mg Oxazepam 15 mg Temazepam 10 mg Zaleplon 10 mg Zopiclone 7.5 mg Zolpidem 10 mg

• Convert current BZD into diazepam

equivalent units

• Switch to once daily BZD, and then

taper (discussed later)

• Diazepam recommend because of a

specific benefit – long-acting

• Alternative BZDs – chlordiazepoxide

and clonazepam

• Adjunct, alternate drugs to potentially

utilize—gabapentin, pregabalin, carbamazepine, etc.

BZD Withdrawal Guidelines: UK Guidelines on Clinical Management (cont’d)

Department of Health (England) and the Devolved Administrations. Drug Misuse and Dependence: UK Guidelines on Clinical Management. 2007. www.nta.nhs.uk/uploads/clinical_guidelines_2007.pdf. Accessed June 5, 2017. Lader M. Addiction. 2011;106(12):2086-2109.

How to Best Taper Off a BZD:

Opposite to Country Western Dance – Quick Quick – Slow Slow!

Lader M. Addiction. 2011;106(12):2086-2109.

DOSE TIME

”The early stages of withdrawal are easier to tolerate than the later and last stages.”

Lader M, et al. CNS Drugs. 2009;23(1):19-34.

Possible Medications to Help with BZD Taper and Withdrawal

The use of carbamazepine, pregabalin, and gabapentin for this indication is off-label. Schweizer E, et al. Arch Gen Psychiatry. 1991;48(5):448-452. Oulis P, et al. Hum Psychopharmacol. 2008;23(4):337-340. Crockford D, et al. Can J Psychiatry. 2001;46(3):287.

Carbamazepine Pregabalin Gabapentin

Note: Pregabalin and Gabapentin themselves have abuse / dependence risk. Keep this in mind if selecting these agents

Focus on CBT and Psychoeducation

CBT

Model of CBT

CBT = cognitive-behavioral therapy.

What we think affects how we act and feel What we feel affects what we think and do What we do affects how we think and feel

This Isn’t Sound Advice!

Nonsense! As long as you take it every day on schedule, you won’t have to worry about addiction!

Is Psychoeducation Worth the Time and Effort?

McGill Experience: Using Psychoeducation Materials Produces Positive Results

http://criugm.qc.ca/images/stories/les_chercheurs/risk_ct.pdf. Accessed June 5, 2017.

The McGill Experience: Study Results

Tannenbaum C, et al. JAMA Intern Med. 2014;174(6):890-898.

261 participants – 86% completed the 6-month follow-up 62% initiated conversation about BZD therapy cessation with physician and / or pharmacist At 6-month follow-up, 27% of intervention group discontinued BZDs At 6-month follow-up, 5% of control group discontinued BZDs Dose reduction occurred in an additional 11%

ALL Patient Profiles Benefitted from Psychoeducation and Slow Taper

Tannenbaum C, et al. JAMA Intern Med. 2014;174(6):890-898.

These factors did NOT influence BZD therapy discontinuation:

• Age > 80 years
• Sex
• Duration of use
• Indication for use

dose

• Previous attempts to

taper

• Concomitant

pharmacotherapy with ≥ 10 drugs/day

Withdrawing/Tapering Use CBT to Improve Outcomes: A Canadian Experiment

Baillargeon L, et al. CMAJ. 2003;169(10):1015-1020.

• People with chronic insomnia who had been

taking a BZD every night for > 3 months

• Randomly

assigned to CBT plus gradual tapering or gradual tapering alone; CBT was provided by a psychologist in 8, weekly, small group CBT sessions

• Tapering was supervised by a physician, who met

weekly with each participant over an 8-week period

• Main outcome measure was BZD discontinuation,

confirmed by blood screening performed at each of 3 measurement points (immediately after completion of treatment and at 3- and 12-month follow-ups)

CBT Add-On, Short- and Long-Term Results

Baillargeon L, et al. CMAJ. 2003;169(10):1015-1020.

At 3 months

Discontinuation rate w/o CBT Discontinuation rate w/ CBT OR improvement 38% 77% 5.3

Results at 12-Month Follow-Up

Baillargeon L, et al. CMAJ. 2003;169(10):1015-1020.

Discontinuation rate w/o CBT Discontinuation rate w/ CBT OR improvement 24% 70% 7.6

Conclusion: CBT is a logical add-on to BZD taper/discontinuation plan

CBT and BZD Discontinuation

TAU = taper as usual; IRT = individual relaxation treatment. Otto MW, et al. Behav Res Ther. 2010;48(8):720-727.

RCT (N = 47) designed to compare the efficacy of 3 strategies for discontinuation of BZD

• treatment. Outpatients with panic disorder randomized to: 1) Conservative taper program

alone, 2) Taper program plus individual relaxation treatment, or 3) Taper program plus individual exposure-based CBT.

Intervention BZD-Free Status at 3-month follow-up BZD-Free Status at 6-month follow-up

TAU 26.7 26.7 TAU + IRT 12.5 12.5 TAU + CBT 43.7 62.5

Adjunctive CBT significantly increased the rates of successful BZD discontinuation relative to taper alone by the 6-month follow-up. No evidence of a worsening of panic in the CBT group at the post-taper evaluations

Combined Psychoeducation + CBT

Great Resources for BZD Tapering

In Conclusion

A Clinic’s Experience with Initiating a Benzodiazepine Safety Initiative

Mission Ensuring the provision of accessible, efficient and effective services supporting the health, dignity and independence of those we serve.

In Conclusion Part I:

BZDs ARE Indeed Effective Medications

Lader M. Addiction. 2011;106(12):2086-2109.

Treatment Guidelines do indeed recommend the judicious use of these medications Patients often use them without issue and long-term Creating a “fear mongering” environment regarding BZD use ultimately backfires and patients suffer as a result

In Conclusion Part II:

But on the Other Hand, Caution is Necessary

Lader M. Addiction. 2011;106(12):2086-2109.

“The practical problems with benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies”

Between 1969 and 1982, diazepam was the most prescribed drug in America with more than 2.3 billion tablets sold in 1978 It is clear that official recommendations concerning the use of these medicines are widely ignored

Top 3 Practical Take-Aways

• 1. Before using BZDs in any patient, a careful short-

and long-term assessment of the risk-benefit is a necessity

• 2. Data is accumulating that risk of addiction and

physical dependence of this class of medications is higher than originally anticipated

• 3. If a decision to slowly reduce or stop these

medications is made in conjunction with the patient, there are now several well-studied pathways available to achieve this goal

Resources

BZDs: How They Work and How to Withdraw

(aka The Ashton Manual)

Medical Research Information from a BZD Withdrawal Clinic

Ashton CH. Benzodiazepines: How They Work And How To Withdraw. August 2002. www.benzo.org.uk/manual/bzcha01.htm. Accessed June 5, 2017.

• Ashton Manual Index Page
• Contents Page
• Introduction
• Chapter I: The benzodiazepines: what

they do in the body

• Chapter II: How to withdraw from

benzodiazepines after long-term use

• Chapter II: Slow withdrawal schedules
• Chapter III: Benzodiazepine

withdrawal symptoms, acute and protracted