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A review on Benzos

A review on Benzos. Gilles Fleury, MD, FRCPC Psychiatrist Montfort Hospital Assistant Professor Education Director – Division of addiction and mental health Department of Psychiatry University of Ottawa October 2016. Disclosure. No conflict of interest. Acknowledgements.

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A review on Benzos

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  1. A review on Benzos Gilles Fleury, MD, FRCPC Psychiatrist Montfort Hospital Assistant Professor Education Director – Division of addiction and mental health Department of Psychiatry University of Ottawa October 2016

  2. Disclosure • No conflict of interest

  3. Acknowledgements • Ralph Dell’Aquila MDCM, CCFP, MRO, ABAM and other presenters • Christine Landry, Pharmacist, Montfort Hospital, Ottawa, ON

  4. Objectives • Why can BZD use be problematic ? • When is BZD use problematic ? • What can we do about problematic BDZ use? • Describe detoxification approache Detox 101: How to Get Patients Off Benzo's and Alcohol  Idenfify whether your pafient is dependent on alcohol or benzo; Detox 101: How to Get Patients Off Benzo's and Alcohol  Develop a plan to help pafients taper and stop drinking;  Idenfify whether your pafient is dependent on alcohol or benzo; Detox 101: How to Get Patients Off Benzo's and Alcohol  Develop an approach to detox;  Develop a plan to help pafients taper and stop drinking;  Idenfify whether your pafient is dependent on alcohol or benzo;  Idenfify available resources for dependent pafients  Develop an approach to detox;  Develop a plan to help pafients taper and stop drinking;  Idenfify available resources for dependent pafients  Develop an approach to detox;  Idenfify available resources for dependent pafients

  5. Benzodiazepines (BZD): mechanism of action • Enhance GABA activity • GABA is the major inhibitory neurotransmitter of the CNS, it decreases neuronal excitation • GABAA : depressant effect • Benzodiazepine (Bz) receptors: • Bz1: Sleep-inducing effect • Site of action of zolpidem • Bz2 and Bz3 : antiseizure, antianxiety and muscle relaxation effects

  6. BZD - Therapeutic uses • Anticonvulsant • Muscle Relaxant • Cerebral palsy, dystonia • Amnesia with Sedation • Peri-operative or medical procedures • Alcohol withdrawal • Insomnia • Acute agitation

  7. BZD - Therapeutic uses -Psychiatric • Severe acute anxiety * Not first line treatment for anychronicanxietydisorder • Severegeneralizedanxietydisorderunresponsive to othertreatments • Panic disorder, social phobia • Adjunctivetreatment of depression, bipolar affective disorder and schizophrenia

  8. Benzodiazepines: Why taper? • Usually not because patient “addicted” • Possible 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 • Need to be aware of comorbid medical conditions and consider physiological stress to patients of tapering, patients with chronic medical conditions experience withdrawal more severely

  9. Benzodiazepines: Adverse Effects ACUTE • Sedation (depressant) • Decreasedrespiratory drive • Overdose (withotherdrugs - esp. alcohol and opioids) • Disinhibition CHRONIC • Decreased Neurocognition • Physiologic Dependency: Tolerance, Withdrawal • Addiction (Intoxication Syndromes)

  10. When is BZD use problematic? Risk Factors for BZD abuse • Comorbid substance use disorders • 80% of BZD abuse part of polydrug abuse • 40% of alcohol abuse • Psychiatric comorbidities: (PD, chemical coping) • Genetic vulnerability (tolerance) • Environmental factors • Pharmacodynamics of BZD (most reinforcing BZD)

  11. Risk Evaluation & Management Strategies Benzodiazepines—Side Effects, Abuse Risk and Alternatives Longo et al. Am FamPhysician. 2000 Apr 1;61(7):2121-2128. • Assessment of Risk Factors • Treatment Goals • Treatment Agreement • Care Plan • Medical Monitoring: • Reassess comorbidites & Diagnoses • How is Functional Status Progressing? • Progress in Behavioural Therapies ? • Management: Have a Plan to manage Complications

  12. Addressing problematic bdz use:Implement rems & safe prescribing guidelines • Other sedating drugs • COPD, sleep disorders • Elderly (esp long acting) • Liver dysfunction • Comorbidities are the rule, not the exception • If prescribing: careful assessment, care plan, Rx goals medical monitoring management: • Have a plan to reassess ++ & manage complications • Should clearly state intended short term nature and dependence potential

  13. Benzodiazepine withdrawal • The clinicalpicture looks like a reboundhyperexcitabilitywith: • body changes in a direction opposite to thatseenwith the first administration of the drug • Time course: • Acute syndrome: • For Short-acting BZDs (lorazepam, oxazepam), 3 to 7 days • Longer for longer acting drugs (e.g. diazepam) • Protractedwithdrawal: less intense symptoms for 3-6 months

  14. Benzodiazepine withdrawal • Symptoms are likely to include: • Headaches and anxiety (80%) • Insomnia (70%) • Tremors (60%) • Fatigue (60%) • Perceptual changes • Tinnitus • Sweating • Decrease concentration • Abrupt abstinence after higher doses could cause delirium and seizures

  15. 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 / COMPLICATIONS • Autonomic hyperactivity (diaphoresis, tremor, tachycardia, HTN) • Hyperreflexia, • Mydriasis • Seizures, Arrythmias • Psychosis, Delirium • Suicidal Ideation

  16. BZD withdrawal Khong E, Sim MG, Hulse G.Benzodiazepine Dependence. Aust Fam Physician. 2004 Nov;33(11):923-6 • Factorsinfluencingseverity: • Duration of drug use • Doses used • Drug half-life • Individualpersonality style • Expectionsfrom patient and physician

  17. Treatment of BZD withdrawal • Good physical exam / screening investigations • Consider inpatient detoxification (hospital setting) • If using diazepam ≥ 60 mg / day OR unknown dosage • If outpatient, taper BZDs over 1 to 6 month-duration • On average, taper over 8 to 12 weeks • If too long, withdrawal becomes ‘the morbid focus of the patient’s existence’ • Either use the same BZD for taper or convert to long-acting (e.g. diazepam or chlordiazepoxide)

  18. Treatment of BZD withdrawal Converting to diazepam

  19. Treatment of BZD withdrawal • Treatment agreement on schedule and process • « weagreethat the goal iszero BZD » • Weekly dispensing of medication if necessary • No BZD PRN during the taper • Close monitoring of the patient during the taper • Monitor increasealcoholconsumtion/ otherdrug use • Non-pharmacological intervention for anxiety • Patient to keep a diary of symptoms and triggers • CBT (targetingunderlying condition) • Physical exercise • Relaxation techniques • Sleephygiene

  20. BZD withdrawal - schedule

  21. Basic principles in primary care Psychoeducation Techniques to deal with anxiety and insomnia Letter from the GP suggesting ↓ in the use of BZD Acknowledge that withdrawal could be stressful Advise changes in lifestyle such as physical activity Avoid stimulants and alcohol Refer to support group Refer to specialized program / agency

  22. Treatment of BZD withdrawal • Potential pharmacological agents to consider: • Carbamazepine: some evidence, but not enough to systematically recommend • 200 to 800 mg / day • Valproic acid (250 mg TID) / Gabapentin / Trazodone • SSRIs: if there is an underlying untreated anxiety / mood disorder • Was the patient depressed or anxious before the dependence? • Remember: • There is no medication approved for chronic insomnia

  23. Discontinuation

  24. Resources • benzo.org.uk by Professor Heather Ashton • information about the effects that BZDs have on the brain and body and how these actions are exerted • Detailed suggestions on how to withdraw after long-term use and individual tapering schedules for different BZDs are provided • http://www.open-pharmacy-research.ca/ • Deprescribing algorithm • Deprescribing.org

  25. Are z drugs addictive? 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 • Z drugs: Zoplicone (Imovane), zolpidem (Ambien) • Non-BDZ • Onset: T1/2 • Abuse potential: lower than BDZ ; • incr risk in SUD & Psych

  26. Questions / Discussion Thank you!

  27. gfleury@montfort.on.ca Thank you

  28. References Denis et al. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev. 2006 Jul 19;(3) Gould RL et al. Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials. Br J Psychiatry. 2014 Feb;204(2):98-107 Khong E, Sim MG, Hulse G.Benzodiazepine Dependence. Aust Fam Physician. 2004 Nov;33(11):923-6 Lader M1, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. Expert Opin Investig Drugs. 2012 Jul;21(7):1019-29.

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