Using Benzodiazepines in Primary Care

Transcription

1 Using Benzodiazepines in Primary Care Spencer A. Tighe MD, FRCPC Saturday, Feb. 16, 2008

2 Overview Historical context Drug information Indications Side effects Abuse vs. physical dependence Clinical practice pearls Resources Q & A

3 Historical perspective They were great in the 60 s but now?

4 Over the past 40 years (1) Prescribed to over 100 million people Symptom relief (part of many Dx) Mostly for anxiety and insomnia Initially compared to TCAs and barbiturates Many anxiety disorders were not considered as true diagnoses

5 Over the past 40 years (2) Negative public attitudes in 1980s and 1990s due to Over prescription without clear diagnostic guidelines for anxiety disorders Abuse potential (patients liked the feeling on meds) Risk of physical dependency (tolerance to dose and withdrawal syndrome)

6 Drug Information Getting to know the family

7 The chemical slide (1)

8 Classifying benzodiazepines (1) I Potency (ability to attach to receptor) (small dose with big effect) Low, Medium and High II Elimination half-life (cleared fast = >> risk of withdrawal syndrome and dependency)

9 Low potency benzos: Chlordiazepoxide (5, 10, 25 mg) Oxazepam (10, 15, 20 mg) Temazepam (15, 30 mg) (Librium) (Serax) (Restoril)

10 Medium potency benzos Chlorazepate (3.5, 7.5, 15 mg) Diazepam (2,5, 10, 15 mg) Flurazepam (15, 30 mg) (Tranxene) (Valium) (Dalmane)

11 High potency benzos Alprazolam (Xanax) (0.25, 0.5 mg) Bromazepam (Lectopam) (1.5, 3, 6 mg) Clonazepam (Rivotril) (0.5, 2 mg) Lorazepam (Ativan) (0.5, 1, 2 mg) Triazolam* (Halcion) d/c (0.125, 0.25 mg)

12 Long Elimination half-life Diazepam (30 100h) rapid action ++ active metabolites (incl. temazepam and oxazepam) slow elimination Clonazepam (20-80 h) no active metabolites

13 Long Elimination half-life Lower chance of withdrawal and dependency Greater chance of accumulation and hang over feeling next day

14 Short Elimination half-life Alprazolam (6 20h) Lorazepam (10 20h) (no active metabolites) Triazolam* (ultra short 2 6 hours)

15 Short Elimination half-life Lower risk of accumulation and morning hangover Greater risk of breakthrough symptoms, rebound symptoms and withdrawal syndrome

16 Drug Actions CNS action at benzo-gaba receptor site Increases GABA activity (inhibitory neurotransmitter action in brain) Hypnotic: induces sleep Anxiolytic: Anticonvulsant: Myorelaxant: Amnestic:

17 Indications What can I use them for?

18 Approved indications Mild to moderate anxiety, tension, excitation and agitation (not diagnosis specific) Generalized Anxiety Disorder Acute and chronic alcohol withdrawal Panic disorder + agoraphobia (Xanax and Tranxene) Insomnia Restless leg syndrome Dystonia, muscle spasms Epilepsy Tetanus Preoperative, peri-operative procedures

19 Plus: (not approved) Drug induced akathisia, movements Mania (adjunct TX) Psychosis Social Phobia Premenstrual Dysphoric Disorder Acute agitation, aggression

20 Down side May make some things worse: Some evidence that early use post-trauma may increase incidence of PTSD Might make depressive symptoms worse (aside from alprazolam)

21 Side effects

22 General concept benzo side effects are mostly related to their desired action (too much of a good thing ) Not a separate action, such as: carbamazepine on bone arrow TCAs on cardiac conduction

23 Action = Side effects Hypnotic/sleep: Anxiolytic/sedative: Anticonvulsant: Myorelaxant: Amnestic: Fatigue, drowsiness, Sedation, visiospatial pbm w/d seizures, CNS depression Ataxia, <motor coordination Memory, cognitive problems

24 What about cognitive impairment? Anterograde amnesia might occur (90 minutes after dosing) Cognitive problems might be associated with sedation / decreased attention Chronic use associated with cognitive problems beyond those of the underlying illness PET / MRI scan research does not show any brain changes due to chronic use POINT: inform patients of this side effect risk

25 Abuse vs. dependence Need to clarify terms

26 Benzo abuse Benzo abuse is like abuse of any chemical Remember to take a history of alcohol and other substance abuse (patient and their family)

27 Substance Abuse Maladaptive pattern of any substance use Clinically significant impairment / distress Use causing 1 + within 12 month period: Failure to fulfill obligations (work, school, home ) Physically hazardous situation (DUI..) Recurrent legal problems Continued used despite psychosocial problems Not substance dependence

28 vs Physical dependence Seen with many medications: (read: SSRIs, SNRIs) Tolerance (< effect and > amount needed) i.e. need to titrate the dose upward over time Withdrawal (substance-specific syndrome) Need to slowly decrease / discontinue medication Does not imply: Lack of efficacy may still be helpful Physical danger Negative impact on psychosocial functioning

29 vs Substance Dependence disorder Maladaptive pattern of substance use Clinically significant impairment / distress Use causing 3+ within 12 month period: Tolerance (< effect and > amount needed) Withdrawal (substance-specific syndrome) > amounts and > time using Continued desire to use and out of control > time obtaining substance Activities given up to use Still using while knowing it s a problem

30 Withdrawal syndrome Anxiety Irritability Insomnia Hyperacusis Nausea Poor concentration Tremour Depersonalization Hyperesthesia Myoclonis Delirium Seizures

31 Clinical Practice Pearls take home messages

32 Think acute illness model Benzos work their best if the symptoms are transient, episodic, and have clear environmental precipitants If symptoms are part of a chronic, persistent disorder, first line TXs are usually not benzodiazepines

33 Think like Rx ing opiates Generally well tolerated Quick acting, good symptom control Good for acute symptoms - chronic symptoms need med review Not for everyone abuse potential Side effects related to excess drug activity Withdrawal syndrome similar to indication Regular TX monitoring needed (similar regulation by government)

34 Think Is there a better alternative? Insomnia: Brief, occasional (e.g. Travel) 7 10 days, Chronic insomnia? sleep study, consider newer agents first (Imovane, etc. Desyrel) Generalized Anxiety Disorder: may be an option, even long term Panic disorder: acute TX with benzo add SSRI taper as Social phobia: Can be effective if used on irregular, context-specific Simple phobia: Can be helpful for flying, performance, etc.

35 Think Red Flags (1) The elderly more metabolites, slower clearance = accumulation = >> side effects >> sedation = falls Memory / confusion = review meds Sleep apnea Benzos contraindicated - make this worse

36 More Red Flags (2) Pregnancy All freely cross placenta T1 teratogenicity possible (>> cleft palate) T3 Fetal Benzodiazepine Syndrome (floppy, temp. problems and withdrawal syndrome) Breast feeding 7 13 % into milk Can cause lethargy and temperature regulation problems Physical dependency Regular review of doses watch for increases (only < 2% do if abuse is not an issue)

37 Resources

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43 WWWs

44 If in doubt

45 Questions?