s tighe benzos 2008 02 16 · clonazepam (rivotril) (0.5, 2 mg) lorazepam (ativan) (0.5, 1, 2 mg)...
TRANSCRIPT
Using Benzodiazepinesin Primary Care
Spencer A. Tighe MD, FRCPC
Saturday, Feb. 16, 2008
OverviewHistorical context Drug informationIndicationsSide effectsAbuse vs. physical dependenceClinical practice pearlsResourcesQ & A
Historical perspective
They were great in the 60’s …but now?
Over the past 40 years … (1)
Prescribed to over 100 million people
Symptom relief (part of many Dx)Mostly for “anxiety” and insomniaInitially compared to TCAs and barbituratesMany anxiety disorders were not considered as “true” diagnoses
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)
Drug Information
Getting to know the family …
The “chemical” slide … (1)
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)
Low potency benzos:
Chlordiazepoxide (Librium)(5, 10, 25 mg)
Oxazepam (Serax)(10, 15, 20 mg)
Temazepam (Restoril)(15, 30 mg)
Medium potency benzos
Chlorazepate (Tranxene)(3.5, 7.5, 15 mg)
Diazepam (Valium)(2,5, 10, 15 mg)
Flurazepam (Dalmane)(15, 30 mg)
High potency benzosAlprazolam (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)
Long Elimination half-life
Diazepam (30 – 100h)
rapid action++ active metabolites
(incl. temazepam and oxazepam)
slow elimination
Clonazepam (20 - 80 h)
no active metabolites
Long Elimination half-life
Lower chance of withdrawal and dependency
Greater chance of accumulation and “hang over” feeling next day
Short Elimination half-life
Alprazolam (6 – 20h)
Lorazepam (10 – 20h)
(no active metabolites)
Triazolam* (ultra short – 2 – 6 hours)
Short Elimination half-life
Lower risk of accumulation and morning hangover
Greater risk of breakthrough symptoms, rebound symptoms and withdrawal syndrome
Drug Actions …
CNS action at benzo-GABA receptor siteIncreases GABA activity(inhibitory neurotransmitter action in brain)
Hypnotic: induces sleepAnxiolytic: Anticonvulsant:Myorelaxant:Amnestic:
Indications
What can I usethem for?
Approved indications
Mild to moderate anxiety, tension, excitation and agitation (not diagnosis specific)
Generalized Anxiety DisorderAcute and chronic alcohol withdrawalPanic disorder + agoraphobia (Xanax and Tranxene)InsomniaRestless leg syndromeDystonia, muscle spasmsEpilepsyTetanusPreoperative, peri-operative procedures
Plus: (not approved)
Drug induced akathisia, movementsMania (adjunct TX)PsychosisSocial PhobiaPremenstrual Dysphoric DisorderAcute agitation, aggression
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)
Side effects
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 arrowTCAs on cardiac conduction
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
What about cognitive impairment?
Anterograde amnesia might occur (90 minutes after dosing)Cognitive problems might be associated with sedation / decreased attentionChronic use associated with cognitive problems beyond those of the underlying illnessPET / MRI scan research does not show any brain changes due to chronic use
POINT: inform patients of this side effect risk
Abuse vs. dependence
Need to clarify terms …
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)
Substance Abuse
Maladaptive pattern of any substance useClinically significant impairment / distressUse causing 1 + within 12 month period:
Failure to fulfill obligations (work, school, home …)Physically hazardous situation (DUI ..)Recurrent legal problemsContinued used despite psychosocial problems
Not substance dependence
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 helpfulPhysical dangerNegative impact on psychosocial functioning
vs Substance Dependence disorder
Maladaptive pattern of substance useClinically significant impairment / distressUse causing 3+ within 12 month period:
Tolerance (< effect and > amount needed)Withdrawal (substance-specific syndrome)> amounts and > time usingContinued desire to use and out of control> time obtaining substanceActivities given up to useStill using while knowing it’s a problem
Withdrawal syndrome
AnxietyIrritabilityInsomniaHyperacusisNauseaPoor concentration
TremourDepersonalizationHyperesthesiaMyoclonisDeliriumSeizures
Clinical Practice Pearls
take home messages …
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 …
Think “like Rx’ing opiates”
Generally well toleratedQuick acting, good symptom control Good for acute symptoms - chronic symptoms need med reviewNot for everyone – abuse potentialSide effects related to excess drug activityWithdrawal syndrome similar to indication
Regular TX monitoring needed
(similar regulation by government)
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.
Think “Red Flags” (1)
The elderlymore metabolites, slower clearance = accumulation = >> side effects>> sedation = fallsMemory / confusion = review meds
Sleep apneaBenzos contraindicated - make this worse
More “Red Flags” (2)
PregnancyAll freely cross placentaT1 teratogenicity possible (>> cleft palate)T3 Fetal Benzodiazepine Syndrome
(floppy, temp. problems and withdrawal syndrome)
Breast feeding7 – 13 % into milkCan cause lethargy and temperature regulation problems
Physical dependencyRegular review of doses – watch for increases (only < 2% do if abuse is not an issue)
Resources
WWWs …
www.benzo.org.uk
www.racgp.org.au/guidelines/benzodiazepines
www.psychiatrist.com
Questions ?