The Identification and Management of

Benzodiazepine Abuse: A Primary Care Approach Ralph Dell’Aquila MDCM, CCFP, MRO, ABAM Northern Ontario School of Medicine North Bay Regional Health Centre Nurture North MAR Clinic With thanks to: Drs. Meador, Hering and other past presenters FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

Faculty/Presenter Disclosure Faculty: Ralph Dell’Aquila MD, CCFP, ABAM  Relationship with commercial Interest ◦ Grants/Research Support: NOSM, ◦ Speakers Bureau/Honoraria: Past Participation Advisory Board, Reckitt Benckiser (travel & lodging) ◦ Consulting Fees: None ◦ Speaker Fees: None ◦ Other: Volunteer Work with Non-Profit Agencies that may be recipients of arms-length unrestricted educational grants from government & industry 

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

Disclosure of Commercial Support 

This presentation : ◦ No Financial support. No speakers fee. ◦ In-kind support from CSAM in the form of logistical support.



Potential for Conflicts of Interest: ◦ No funding from any organization whose products are being discussed in program. ◦ Supporting organizations developed/licenses/distributes/benefits from the sale of a product that may be discussed in this program: ◦ Cf CSAM program list of Corporate Booths

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

Mitigating Potential Bias 

Mitigation of potential sources of bias: ◦ Disclosure of relationships with commercial interests ◦ Knowledge transfer of Evidence-based Literature ◦ Knowledge transfer of Specialty clinical Experience ◦ No endorsements of commercial products ◦ Identify off-label use

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

CASE PRESENTATION •

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• • • •

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Joanne: 44 yr old woman Fatigue, Lassitude, depression, obesity, metabolic syndrome, fibromyalgia, chronic LBP Laid off 4 yrs ago. ODSP. Meds: OxyContin+ Percocet 12/day for breakthru pain Valium 10 mg qid (multiple BDZ’s, multiple MD’s) Celexa, mirtazepine, quetiapine, Gabapentin

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

CFPC LEARNING OBJECTIVES Understand mechanism of BDZ action Understand neuroscience of BDZ addiction Understand BDZ pharmacology Assess BDZ use disorders Assess & manage BDZ intoxication Assess & manage BDZ withdrawal Understand the comprehensive treatment of BDZ addiction within context of Chronic Disease Model

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

OUTLINE 1.

Why can BDZ use be problematic ?

2.

When is BDZ use problematic ?

3.

What can we do about problematic BDZ use?

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

WHY CAN BDZ BE ABUSED ? GABA major inhibitory CNS neurotransmitter •

decreases neuronal excitation

• BDZ potentiate

effects of GABA-R • BDZ metabolism 3A4 • Inc T1/2: • Elderly, liver Dz Many BDZ’s have active metabolites GABA vs Glutamate balance FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BDZ (Duration Action)

Onset of effect

Equivalence to 5mg diazepam

Elimination t1/2

Active Metabolites

Short 24h Flurazepam (Dalmane)

fast

7.5-15

50-100h

Yes

Diazepam (Lorazepam)

fast

5mg

20-100h

Yes

Clonazepam (Rivotril)

intermediate

0.5-1

17-50h

No

Chlordiazepoxide (Librium)

intermediate

10-25

7-25h

Yes

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

THERAPEUTIC USES Medical Anticonvulsant, Muscle Relaxant • Cerebral palsy, dystonia Amnesia with Sedation: surgical procedures

•

•

Psychiatric • • • • • •

•

Acute agitation Alcohol withdrawal Insomnia Acute Agitation Severe acute anxiety Severe anxiety disorder unresponsive to other treatments (3rd line rx) Adjunctive treatment of depression, bipolar affective disorder and schizophrenia FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BDZ Not first line treatment for any chronic anxiety disorder

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Continuum of Substance Use

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BENZODIAZEPINES: ADVERSE EFFECTS •

Acute:

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Sedation (depressant)

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Decreased respiratory drive

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Overdose (with other drugs- esp. alcohol and opioids Disinhibition

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•

Chronic: Decreased Neurocognition

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Physiologic Dependency: Tolerance, Withdrawal

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Addiction (Intoxication Syndromes, 4 C’s)

•

1 FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BENZODIAZEPINES: ADVERSE EFFECTS Cognitive Effects of Long-Term Benzodiazepine Use

Several studies demonstrate cognitive dysfunction  Impairments in visuospatial ability, verbal learning & memory  Associated with decreased functional status  controversial 

The effects of benzodiazepines on cognition. Stewart, S. J Clin Psychiatry. 2005;66 Suppl 2:9-13. Cognitive Effects of Long-Term Benzodiazepine Use: A meta-Analysis. Barker, et al. CNS Drugs 18(1) pp37-48

1 FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

2. WHEN IS BDZ USE PROBLEMATIC ? Risk Factors for BDZ abuse 1.

Comorbid substance use disorders 80% of BDZ abuse part of polydrug abuse (Gold et al. Psych Annals, 1995). 40% of alcohol abuse

Psychiatric comorbidities: (PD, chemical coping) 3. Genetic vulnerability (tolerance) 4. Environmental factors 5. Pharmacodynamics of BDZ (most reinforcing BDZ) 2.

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BDZ DEPENDENCY 

Rate of CNS Entry & CNS Potency increases Risk

Higher Dependence Risk

Lower Dependence Risk

Alprazolam (Xanax)

Oxazepam (Serax)

Triazolam (Halcion)

Chlordiazepoxide (Librium)

Lorazepam (Ativan)

Clonazepam (Rivotril)

Diazepam (Valium)

Zoplicone (Imovane)

http://nnadaprenewal.ca/wp-content/uploads/2013/03/4CCSA-Prescription-Sedatives-and-Tranquilizers-2013-en.pdf FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

ARE Z DRUGS ADDICTIVE? •

• • • •

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3 groups: cyclopyrrolones (zoplicone), imidazopyridines (zolpidem), pyrazolpyrimidines (zaleplon) Non-BDZ CNS sedative-hypnotic Different binding to GABA receptor Rapidly absorbed, T1/2 3-7 hrs Abuse potential: lower than BDZ ; • incr risk in SUD & Psych Documented tolerance, dependence, w/d & abuse • incr risk in SUD & Psych

Abuse and dependence of zopidem and zoplicone. Hajak et al. Addiction 2003 98:1371-78 Zoplicone: Is it a pharmacolgic agent for abuse? Cimolai, N. Cdn Family Physician Dec 2007:53(12) 2124-2129

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3. RISK EVALUATION & MANAGEMENT STRATEGIES 1.

Assessment of Risk Factors

2.

Treatment Goals

3.

Treatment Agreement

4.

Care Plan

5.

Medical Monitoring: • Reassess comorbidites & Diagnoses •

How is Functional Status Progressing?

• Progress in Behavioural Therapies ?

6.

Management: Have a Plan to manage Complications

http://www.patient.co.uk/doctor/Benzodiazepine-Dependence.htm FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

3. ADDRESSING PROBLEMATIC BDZ USE:

BDZ SAFE PRESCRIBING GUIDELINES • Assess Risk Factors: • Other sedating drugs • COPD, sleep disorders • Elderly (esp long acting) • Liver dysfunction • Comorbidities are the rule, not the exception • Clearly state intended short term nature & dependence potential

Benzodiazepines—Side Effects, Abuse Risk and Alternatives Longo et al. Am Fam Physician. 2000 Apr 1;61(7):2121-2128. 1 FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

MANAGEMENT OF BENZODIAZEPINE ADDICTION Recognize abuse, misuse, overuse & abuse cycles 2. Recognize+manage intoxication syndrome 3. Recognize withdrawal syndrome 4. Benzodiazepine withdrawal management 1. Inpatient vs outpatient 5. Implement safer alternatives to BDZ of abuse 6. Motivational interviewing (Stages of Change) 1.

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BENZODIAZEPINE (BDZ) WITHDRAWAL • All BDZ can cause physical dependence and withdrawal • May be subacute, prolonged waxing and waning withdrawal

• Including insomnia perceptual disturbances, tremor,

sensory hypersensitivities and anxiety • Spectrum: Mild – Moderate - Severe • Severity Associated with: • T1/2, potency, dose & duration of BDZ • Comorbid medical conditions (liver, cardiac, resp) • Concurrent psychiatric conditions (mood disorders, PD) • Co-addictions (mixed w/d: alcohol, opiates, stimulants)

www.benzo.org.uk FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

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DISCONTINUATION SPECTRUM Symptom Recurence/Relapse

Rebound

Pseudowithdrawal

True Withdrawal

Common Anxiety or Insomnia Can present rapidly or slowly Consider alternative treatment

• • • • • • • • •

Occurs within hours-days Qualitatively more intense Transiently worse than before benzo initiation Short duration and self limited Overinterpretation of symptoms Expectation of W/D lead to experiencing abstinence symptoms Expectation created by physicians and media Symptoms and signs related to physiological dependence Results from a reversal of neuroadaptive changes in the CNS that were induced by chronic Benzo use FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

BENZODIAZEPINE (BDZ) WITHDRAWAL •

Symptoms

• • •

Anxiety-related (irritability, insomnia, panic attacks, hypersensitivity (photo/phono,touch) Neurologic (tinnitus, distorted vision, dysperceptions, tremor) Muscle twitching, insomnia, irritability, decreased concentration

• Signs

• • •

Autonomic hyperactivity (diaphoresis, tremor, tachycardia, HTN) Hyperreflexia, Mydriasis

• Complications (Abrupt cessation of high dose BDZ)

•Seizures, Arrythmias •Psychosis, Delirium •Suicidal Ideation

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

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BENZODIAZEPINES: WHY TAPER? •

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Usually not because patient “addicted” although depends on your setting Benefits of tapering: • •

• • • • •

more alert, energetic better able to make positive life changes not need drug anymore avoid future adverse effects

High risk if concomitant use of other depressants Consider comorbid medical conditions Consider physiological stress of tapering

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

TAPERING: GENERAL PRINCIPLES • • •

• •

Written Treatment & management plan Rx plan: Clear, Continuous, Comprehensive, CMS Develop alternative treatment strategies for managing insomnia and anxiety (both pharmacologic and nonpharma) Implement behavioural therapies: MI,MET, CBT Regular Monitoring, Support & Reassessment • Single prescriber • Contingency Management System (CMS) • Harvard 5 questions

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

OUTPATIENT TAPERING •

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Consider switching to equivalent dose of diazepam or clordiazepoxide (or clonazepam for patients on alprazolam or triazolam) Use scheduled fixed dose and interval taper schedule (not PRN), Taper over 6 weeks to many months (2-5 mg or 10 % of dose / 1-2wk) Decrease rate of taper at doses < 20mg diazepam equivalent (or last 25-35% of of taper), consider ½ the decrease at ½ the rate The diagnosis and management of benzodiazepine dependence Ashton, H. Current Opinion in Psychiatry 2005, 18:249–255 FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

TAPERING: ADJUNCTIVE MEDS 

    

Anxiolytic: Propanolol, clonidine Older Antidepressants: TCA’s, trazadone Newer antidepressants: SSRI, SNRI Anticonvulsants: gabapentin, valproic acid, carbamazepine Muscle relaxants (lioresal) Sleep disorders: lo-dose atypical antipsychotic

1. Roy-Byrne et al. Adjunctive treatment of benzodiazepine discontinuation syndromes: a review. J Psychiatr.Res. 1993;27 Suppl 1:143 - 153. . 2. Reis et al. Principles of Addiction Medicine Chap 47: Pharmacologic Intervention for sedative-hypnotic addiction. 3. Crockford et al. . Gabapentin use in benzodiazepine dependence and detoxification. Can.J Psychiatry. 2001;46(3):287. FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

CONCLUSION 1.

Why can BDZ use be problematic ?

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Similar addiction risks as other prescribed Rx 3 Dz Risk Factors: Host, Environment, Agent High OD risk if used with other depressants especially alcohol or opioids Appropriate and effective for short-term acute situational anxiety: (max days-weeks)

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FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

CONCLUSION 2. 

 

When is BDZ use problematic ?

Chronic use: risks of complications can lead to dependence & addiction subtle negative side effects (sedation etc) ◦ When Close Monitoring reveals : ◦ Declining Functional status & Cognition

FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

2. 

When is BDZ use problematic ? 28 yo 28 yo

28 yo Australian heartthrob Dx: Sleep disorder, anxiety and depression Jan 2008:

Found near corpse in his home (Xanax,Valium, Lunesta, Restoril and Ambien)

Cause of death: acute intoxication by the combined effects of oxycodone, hydrocodone, diazepam, temazepam, alprazolam, doxylamine FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

CONCLUSION 3. What can we do about problematic BDZ use?  



◦ ◦

Address insight & motivation to change Taper should be proposed/attempted in any chronic users, especially if elderly or those abusing other substance Engage in real Recovery of Health Practice Outcome-based EBM Use Behavioural & Relationship Management Strategies: (MI, MET, CMS, CBT, DBT) ◦ Relationship Management Of The Borderline Patient: From FUNDAMENTALS Understanding To Treatment. David Dawson 1993 COURSE CSAM 2014 – OTTAWA

CASE ASSESSMENT •

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Joanne: 44 yr old F Complex comorbidities Medical: metabolic syndrome, NIDDM • obesity BMI 32 Pain: chronic LBP, fibromyalgia, chronic H/A Mental Health: anxiety, mood & sleep disorders Substance Use: nicotine, cannabis, alcohol & BDZ dependencies loss of control of opiates use (addiction) Social: unhealthy social relationships, loss of job Psychological: Coping skills , insight, selfefficacy & resiliency: low FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

Sleep Psychological Traits

Genetics Environment A

A

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CASE PROGRESS & OUTCOME •

1. 2.

3.

4. 5. 6. 7. 8. 9.

Joanne: 2004-2014 Opiate use stabilized on MMT Problematic BDZ overuse during holidays ( repeated admissions polypharmacy qXmas) Motivational Interviewing, Contingency Management & Relationship management Therapeutic groups + pro-social peer groups Co-dependency & trauma issues: leaves husband Meds: BNX, SSRI, pregabalin, d/c BDZ Non-smoker of Cannabis, Nicotine. 1 drink/week Improved Functional Status, QoL, Pain, Cognition BMI: 26 FUNDAMENTALS COURSE CSAM 2014 – OTTAWA

Mindful Active Recovery: 7 WELLths

Social Health Financial WELLth

Psychological Health

Biological Health

Spiritual Health

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Thank You !

Questions ? Nurture North MAR Clinic 239 Main St. East North Bay ON Tel 705-478-7197 Fax 705-478-0861 [email protected] FUNDAMENTALS COURSE CSAM 2014 – OTTAWA