Management of withdrawal

Prof.Dr.Aznan Lelo,PhD,SpFK

Dr.Datten Bangun MSc,SpFK

Dept.Farmakologi & TerapeutikFak.Kedokteran

U S U

Withdrawal Syndrome

The characteristic group of signs and symptoms that typically develop after : = a rapid or = marked decrease or = discontinuation of a substance of dependence, which may or may not be clinically significantly

of life threatening.

The characteristic group of signs and symptoms that typically develop after : = a rapid or = marked decrease or = discontinuation of a substance of dependence,

which may or may not be clinically significantly of life threatening.

Withdrawal SyndromeWithdrawal severity and duration depend

on several factors:

1. Nature of substance2. Half-life and duration of action3. Length of time substance used4. Amount used5. Use of other substances 6. Presence of other medical and psychiatric

conditions 7. Individual biopsychosocial variables

Alcohol Withdrawal

Delirium Tremens

• Approximately 5% of patients withdrawing from alcohol will experience delirium tremens characterized by:– Hallucinations– Disorientation– Tachycardia– Hypertension– Low grade fever– Agitation– Diaphoresis

• Time scale– Minor withdrawal symptoms = 6-12 hours– Alcoholic hallucinations = 12-24 hours– Withdrawal seizures = 24-48 hours– Delirium Tremens = 48-72 hours

• Risk factors for DTs include– History of sustained drinking– History of previous DTs– Age>30– >2 days since the last drink

*Our patient= 17 HIGH!

3

4000

5

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•Minimal to mild= <8•Moderate= 8=15•High= >15

Withdrawal Assessment

Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar)

• Nausea

• Tremor• Diaphoresis• Anxiety• Auditory disturbances• Orientation• Agitation• Tactile disturbances• Visual disturbances• Headaches

Withdrawal Severity: 0 (not present) to 67 (extreme); Higher = >risk

• 8-10 Mild –Supportive, no Meds (i.e. Social Detox)

• 10-15 Moderate - Some meds (BZP) (i.e. Medically Supported Detox)

• 15/> Severe - DT Risk (i.e.. Hospitalization)

N.B. May also be used to monitor recovery and medication management

Treatment• **Benzodiazepines-

• The preferred agents for treating the symptoms of alcohol withdrawal syndrome.

• Diazepam and Chlordiazepoxide are long acting agents. The long half life makes withdrawal symptoms and rebound from the Benzos less likely to occur.

• Ex: Diazepam 5mg IV (2.5mg/min). • If initial dose is not effective, repeat in 5-10minutes.

If the second dose is not effective, use 10mg for 3rd and 4th doses every 5-10 minutes.

• If not effective, use 20mg for the 5th and subsequent doses until sedation is achieved,. Use 5-20mg/hour as needed to maintain light somnolence (5)

With appropriate treatment, mortality rate from DTs is <3%

Alcohol withdrawal treatment

– Short acting benzos like lorazepam may be better for pts who are elderly or have substantial liver disease and prolonged sedation is a risk.

– Diazepam, Lorazepam may be administered parenterally when oral dosing is impossible.

– “Fixed Dose” or “Loading dose” vs. “symptomatic” therapy

• Fixed dose allows “stable” control of symptoms followed by a 4-7 day taper

• Symptomatic- Pts use less benzodiazepines but must have trained/available nurses to administer

Choice of a BZD

Long half-life (chlordiazepoxide, diazepam):

Seizures: ~ 58%

Distress (“smoother detox”)

Shorter half-life (lorazepam, oxazepam)

Oversedation

Safer in elderly / liver impairment

Alcohol withdrawal treatment• B-Blockers in conjunction with benzos to control

persistent HTN and tachycardia. There is no evidence these improve outcome.

• Carbamazepine can be used to treat the seizures, this is done more in Europe than in the US.

• Haldol can be used to treat agitation and hallucinations• Nutrition support: Thiamine to avoid Wernicke-Korskoff,

Mg supplementation, folate if needed.

• Acamprosate, disulfiram appropriate for abstinence therapy NOT withdrawal

DetoxificationAlcohol Withdrawal• Autonomic dysfunction-Insomnia-Anxiety• Onset 8+ hrs, Peak 48hrs, Diminished 5dys, Duration

3-6 months • Withdrawal Syndromes:1. Mild, moderate or life-threatening severity (increased

severity with BAL>100mg/dl)2. 3% Withdrawal Seizures (w/in 48hrs of abstinence)3. Delirium Tremens (DTs) – Medical Emergency! (w/in 48-72hrs of abstinence)

(4-5% Prev., M&M<5% w/o tx, <1% w/tx)

Sample Medication ProtocolDays 1-2 : Lorezepan 1-2 mg three times a dayDays 3-4: Lorezepam 1-2 mg twice dailyDay 5: Lorezepam 1-2mg, daily *Adjust dosage and duration for intoxication or

prolonged withdrawal

• Adjunctive treatments:1. Seizure history: Tegretol 200mg/Neurontin 400mg (5dy taper)2. Sympathetic activity: Clonidine 0.1-0.2q8hrs (3-5dys)3. Fluids, MVI, Thiamine4. Manage co-morbid conditions

Carbamazepine and Valproate• Effective in:

Mild to moderate AW / protracted AW distress and faster return to work No abuse potential / alcohol interactions No toxicity in 7-day trials

• Limitations: Not better than BZDs Side effects Cost Limited data in AW seizures/delirium

Other Agents

• Antipsychotics: seizures, agitation

• -Adrenergic antagonists and clonidine: Autonomic activity, may hide impending

seizures

• Magnesium: levels in AW, supplement does not severity

• Ethyl Alcohol: No evidence of efficacy, toxic + expensive

Nonpharmacological Treatment

• Quiet environment• Nutrition and hydration:

Oral thiamine (prevents Wernicke-Korsakoff) / folic acid

Oral fluids / electrolytes

• Orientation to reality• Brief interventions / motivate to change• Referral to AA / relapse prevention tx.

Conclusions

• AW common complication in AD patients

• Clinicians must screen for AD / AW

• During AW, excitatory neurotramsmission

• If untreated AW can be deadly or lead to morbidity

• BZD most effective, safest and cheapest treatment

BENZODIAZEPINES

General ConsiderationSedative-hypnotic (Benzodiazepine)

Detoxification• Symptoms similar to alcohol but no objective

measure/scoring system• High risk of delirium, seizures and death requires

treatment• Sub-clinical symptoms may persist for months• Tolerance develops within 3-4 weeks of regular

use • Onset of withdrawal symptoms determined by

half-life of compound

BenzodiazepineDetoxification guidelines:• Slow-tapering of the compound or use of a

longer acting benzodiazepine recommended(i.e., Clonazepam TID with 10% tapering daily)

• Sedatives for insomnia (i.e. antidepressants)• Avoid beta blockers (mask symptoms) • Anti-seizure medications adjusted and

monitored

General ConsiderationDetoxification• Symptoms similar to alcohol but no objective

measure/scoring system• High risk of delirium, seizures and death ---

requires treatment• Sub-clinical symptoms may persist for months• Tolerance develops within 3-4 weeks of

regular use • Onset of withdrawal symptoms determined by

half-life of compound

Sedative-hypnotic (Benzodiazepine)

Barbiturate withdrawal

Symptoms may range from rebound insomnia (from hypnotic doses) to delirium and seizures (from higher doses) similar to those of alcohol withdrawal

Management involves substitution of a long-acting benzodiazepine (diazepam) to reduce severity of symptoms and aid in slow and careful tapering off of offending barbiturate

POPPY PLANTSPOPPY PLANTS

OPIATE/OPIOID

Opiate Indications for Use

1. Addiction Maintenance Therapy– Methadone (Pure Mu Opioid Agonist) – Naltrexone (Opioid Antagonist)– Buprenorphine (Opioid Agonist-

Antagonist)– (N.B. LAMM now Minimally Available)

2. Pain Management

Opiate Withdrawal Syndrome1. Not life threatening,

Extremely uncomfortable

2. Symptom onset and duration, half-life dependent

3. Common Sns & Sxs:• Yawning• Sweating• Tearing• Abdominal Cramps

• Nausea and/vomiting• Diarrhea• Weakness• Dilated Pupils• Goose bumps• Muscle twitching aches and

pain• Anxiety• Insomnia• Increased pulse• Increased Resp rate• Elevated Blood pressure

Opiate Detoxification

Key Considerations:• Medical Detoxification = Standard of Care • Methadone short-term substitution therapy =

the preferred method of detoxification, but…• Goal of treatment = reducing withdrawal

discomforts, with or without Methadone or Narcotic Substitution

Opiate DetoxificationLevels of Care

• Inpatient Setting1. Duration: 4-7 days2. Usual dose to suppress

symptoms: 30-40mg/day Methadone

3. Immediate Referral to drug-free treatment setting

4. Clonidine (Catapres) can be considered an effective alternative treatment for inpatient opioid detoxification but not outpatient

• Outpatient Setting1. 21 day protocol

sufficient for most stable, motivated patients

2. 180 day protocol, done within an opioid agonist therapy program, should be considered to work on patients’ early recovery problems, while stabilized on relatively low dose (50-60mg) Methadone

Opiate DetoxificationAdvantages of Methadone• Daily dosing due to 24 hour half-life, requiring

slower tapering schedule • Long half-life safe for all opiates• Safe in pregnancy• May be used in combination with other

medications for co-occurring disorders or mild withdrawal symptoms

• Decreases morbidity and mortality, hepatic damage, and HIV

• Exception: licensing requirements, very addictive

Opiate Detoxification

Methadone Guidelines:• Stabilize Withdrawal: 5-10 mg prn every 4-6

hours to control objective signs of withdrawal• Monitor respiratory depression and

excessive sedation until stabilized• Detoxification: Reduce by 10%/day after

stabilized for 2-3 days• Clonidine 0.1-0.2mg/day for duration

Opiate DetoxificationPharmacological Guidelines

(cont.)Adjunctive Treatments• Nonsteroidal Anti-inflammatory Agents for pain and fever

(i.e. Tylenol, Aleve)• Alpha-adrenergic blocker for sympathetic hyperactivity

such blood pressure, nausea, vomiting, diarrhea, cramps and sweating

(i.e. Clonidine/Catapres)• Antidiarreals and anti-emetics to control gastrointestinal

symptoms (i.e. Bentyl, Phenergan)• Antidepressants/Antipsychotic for dysphoria, anxiety and

insomnia (i.e. Trazedone/Elavil/Seroquel with/without Lexapro)

• Psychotropics for co-morbid psychiatric conditions along with medications for medical conditions

• Used to block autonomic signs and symptoms of withdrawal:

• cramps• nausea• vomiting• tachycardia• sweating• hypertension

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ANS EFFECTS

Clonidine

Motivational:PleasureRewardEuphoria

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2-AR

Clonidine, an agonist at 2-AR.Trea

Treatment of opiate withdrawal

Opiate DetoxificationBuprenorphine

• History: October 2000amended Control Substance Act: 30 patient/MD max for opioid dependence treatment, with DEA waiver; Goal: accessibility, expanded treatment capacity

• Partial mu agonist antagonist: ceiling effect (safer), sublingual absorption, Suboxone preferred

• Dosing instructions dependent on half-life of substituted opiate

• Average tolerable maintenance dose is 4-32 mg SL/day to every 3rd day

• Detox at 10%/day as tolerated

Medically-Assisted Withdrawal (Detoxification)

• Outpatient and inpatient withdrawal are both possible

• How is it done?– Switch to longer-acting opioid (e.g., buprenorphine)

• Taper off over a period of time (a few days to weeks depending upon the program)

• Use other medications to treat withdrawal symptoms

– Use clonidine and other non-narcotic medications to manage symptoms during withdrawal

naloxone (Narcan)

• Competes for opiate receptor sites• Has a shorter duration of action than

narcotics, so it must be given repeatedly

The Clinical AssessmentThe diagnosis of dependence is made through a careful

patient history and physical examination, focusing on the following information:

• Drug type, route and duration of use, symptoms with cessation and last use

• Risk factors, symptoms and previous testing for blood-bourn pathogens

• Past Medical History and review of symptoms of chronic use such as malnutrition, tuberculosis infection, trauma, endocarditis, and sexually transmitted diseases

• Physical Examination to include vital signs, and cardiac status for evidence of fever, heart murmur, or hemodynamic instability; exam should focus on skin areas for scarring, atrophy, infection

• Laboratory Evaluation should include a complete blood count, comprehensive chemistry panel, HIV testing, EKG, Chest x-ray, screening for STD’s

• Urine Drug Screens and Breath Analysis (Alcohol)

Detoxification

The physiological process of withdrawal from a substance of dependence

which requires medication management, careful monitoring, and

the availability of lifesaving emergency interventions.

-Adrenoceptor and Dopamine Receptor Agonists

• Dobutamine • Dopamine

Mechanism of Action: Dobutamine

• Stimulation of cardiac adrenoceptors: inotropy > chronotropy

• peripheral vasodilatation

• myocardial oxygen demand

Mechanism of Action: Dopamine

• Stimulation of peripheral postjunctional D1 and prejunctional D2 receptors

• Splanchnic and renal vasodilatation

Therapeutic Use

• Dobutamine: management of acute failure only

• Dopamine: restore renal blood in acute failure

Adverse Effects

• Dobutamine – Tolerance – Tachycardia

• Dopamine – tachycardia – arrhythmias – peripheral vasoconstriction