Examining the Risks and Benefits from Benzodiazepines

Rakesh Jain, MD, MPHClinical ProfessorDepartment of Psychiatry Texas Tech Health Sciences Center School of MedicineMidland, Texas

Adjunct Clinical AffiliateUniversity of Texas at AustinSchool of NursingAustin, 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 surveyof 8000 people in 2districts of Wales, BZDuse was associated withinjuries outside work andcognitive failures

• The risk of hip fracturesin older adults can beincreased by as much as50%

In a recent Finnish study of patients with or 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 of 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, cognitivedecline, amnesia, impaired psychomotor speed (eg,motor vehicle accidents), and nursing home placement

• Such risks above are of greatest concern among olderadults, who are more sensitive to medicines and mostvulnerable to their consequences

• The pharmacokinetic and pharmacodynamic changes inthe aging body and brain make older patients vulnerable

• As a result, all BZDs are on the list of PotentiallyInappropriate 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 significantincreased 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 substancesthan for short-acting ones

• A trend for increased risk for dementia with higher exposure wasobserved

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 2016Are 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 BZDuse compared with nonuse were 1.25 (95% CI 1.03–1.51) for 1–30TSDDs; 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 minimalexposure to BZDs but not with the highest level of exposure. These results donot support a causal association between BZD use and dementia.

“…given the mixed evidence regarding benzodiazepines and risk of dementiaand that these drugs are associated with many adverse events, healthcareproviders 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 Abuseand Mental Health Services Administration. www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm. Accessed June5, 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 BZDsRose 149% from 2004 to 2011. Alprazolam indicated in~ one-third of visits, and in ~ one-third of BZD-relatedsuicide attempts

ED Visits – BZDs + AlcoholBZDs were involved in 123,572 of the 606,653 ED visitsin 2011 that involved drugs and alcohol taken together(20.4%)

Drug-Related DeathsAlprazolam – 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

only 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 of 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 thepositive 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 neuronsand underlies drug reinforcement

Data provide evidence that BZDs share defining pharmacologic features of addictivedrugs through cell type-specific expression of α1-containing GABAARs in the ventraltegmental 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 andmental dependence can develop in the absence oftolerance

• 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 of 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 associatedwith BZD use, most don’t

• Most treatment guidelines do recommend thejudicious use of BZDs

• The goal of this presentation is not to create “fearmongering” among us clinicians

• Many patients are on long-term BZD therapy anddon’t have problems associated with them. Theyshould not be unnecessarily taken off thesemedications – 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,

overdose 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 seizuresEpilepsy

Centrally muscle-relaxing Central spasticityMuscle tensionTetanus

Muscle asthenia, ataxiaDisturbance of gaitRespiratory depression

Sedative/hypnotic Sleep disturbancesPremedication in

anesthesiology

Diurnal sedationReduced 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

IndifferenceRetreat from realityFlattening 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

LorazepamManagement of anxiety disorders, anxiety symptoms associated with depression

Clonazepam Seizures, panic disorder

DiazepamAnxiety 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 BZDdose by 50% every week or so, to reducing the dailydose by between 10% and 25% every 2 weeks

• A period of 4-to-6 or 4-to-8 weeks is suitable for withdrawalfor most patients

• If possible, prolonged reductions over a period of manymonths should be avoided in order to prevent thewithdrawal 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 majormental disorder who need BZDs for stabilization

• Some elderly patients – as withdrawal can be difficult toachieve 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 canattempt 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 SymptomsFrequency

(%)

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 DisturbancesFrequency

(%)

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 – chlordiazepoxideand 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.

DO

SE

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 NOTinfluence 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 beentaking a BZD every night for > 3 months

• Randomly assigned to CBT plus gradualtapering or gradual tapering alone; CBT wasprovided by a psychologist in 8, weekly, smallgroup CBT sessions

• Tapering was supervised by a physician, who metweekly with each participant over an 8-week period

• Main outcome measure was BZD discontinuation,confirmed by blood screening performed at each of 3measurement points (immediately after completion oftreatment 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 BZDtreatment. Outpatients with panic disorder randomized to: 1) Conservative taper programalone, 2) Taper program plus individual relaxation treatment, or 3) Taper program plusindividual 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 + CBTGreat Resources for BZD Tapering

In Conclusion

A Clinic’s Experience with Initiating a Benzodiazepine Safety Initiative

MissionEnsuring 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 anecessity

2. Data is accumulating that risk of addiction andphysical dependence of this class of medicationsis higher than originally anticipated

3. If a decision to slowly reduce or stop thesemedications is made in conjunction with thepatient, there are now several well-studiedpathways 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