DetoxificationDetoxification

Dr Gholam Reza Kheirabadi

Assistant Professor of Psychiatry

Behavioral Sciences Resaerch Center

Isfahan University of Medical Scienceskheirabadi@bsrc.mui.ac.ir

DetoxificationDetoxification( Medically supervised ( Medically supervised

withdrawal) withdrawal)

-opioid Agents for treating opioid withdrawal.-opioid Agents for treating opioid withdrawal.(Methadone, buprenorphine , LAAM & (Methadone, buprenorphine , LAAM & Tramadol)Tramadol)-Non opioid Approach for Detoxification.Non opioid Approach for Detoxification.(clonidine & lofexidine)(clonidine & lofexidine)

وزن – دولتي شركت يك كارمند سال ميان 76مرديكرده- مراجعه پزشك روان همسرشبه با كيلو

. است . ترياك به مرد اعتياد خانواده مشكل استكه است داروهائي تجويز خواهان ريزان اشك جوان زن

مي . مرد كند اعتياد ترك آنها كمك با بتواند همسرش . تواند مي بخواهد هروقت ندارد چنداني مشكل گويد

. ريز و انكار مكانيسم از افراط حد به نكند مصرف ماده. كند مي استفاده مشكل نمائي

چيست؟ شما توصيه

- معتاد كه زماني به درمان شروع كردن موكول الف. پيداكند كافي انگيزه

انگيزشي – مصاحبه انجام بخانواده – به كمك باهدف زدائي مسموميت شروع ج

انها اگر كه واقعيت واين - نگردند بر هرگز است ممكن بروند

كند – اعتماد شوهرش به گوئيم مي بيمار همسر به داعتياد حد در ومشكل

. نيست

است؟ پذير درمان واقعا اعتياد آيااست؟ آسان و سريع درمان اين آيا

در اعتياد آسان ساعت 48درمانبيزاري؟؟ ايجاد با درد بدون

= ؟؟ درمان زدائي مسموميتدرمان؟؟ = پرهيز

: مراحل مواد وابستگي درمانپرهيز- – 1 آغاز انگيزه ايجادزدائي- 2 مسموميتو- 3 پرهيز ا ادامه درمان آغازدر : صلي شركت درماني روان شروع

( گمنام ( معتادين خودياري هاي گروهتغيراتشخصيتي – زندگي سبك تغيير

زندگي– ونگرشبه عادات تغيير

اول كردن : اصل انفرادي مواد وابستگي درمان در

دوم .اصل نكنيد : استفاده آور اعتياد مواد ازها ديازپين وبنزو افيوني مواد از استفاده اين بر بنا

قاعده ونه است استثنا بيمار؟ كدام روشبراي كدام

روشسنگاپور- 1روشها

تيلن- + 2 تريپ آمي كلونيدينمواد- 3 هاي آگونيست ديگر و متادونافيوني

Individualization

Outpatient Treatment ProgramOutpatient Treatment Program

• Initial stabilization up to cessation of illicit opioids( initial period of abstinence).

• Gradual dose reduction(3%/week is

Superior to 10%/week reduction).• Timetable is superior to free reduction.• More gradual reduction= more successfulness )

• More supervision after 20-30mg/day of methadon

Inpatient Treatment ProgramInpatient Treatment Program

• Initial stabilization fore 24-48 hours( up to 60 mg).

• 10-20% reduction of methadone/day(or 5mg/day)

• Close supervision & supportive resources

• Termination with in 7-10 days

MEHTADONEMEHTADONE

• Stabilization on Methadone:-Initial dose:A:10-20mg→ if withdrawal persist → Repeat the

dose( 2 hours later ) [ no more than 40mg during first day].

B: Calculation of equivalent withdrawal suppressing dose of methadone?

(Methadone is 3time potent than morphine).C: Add 10mg/2-3day or week( different for

outpatient V.S inpatient detoxification?) up to final stabilization(more gradual and upper final

dose in outpatient setting).

Buprenorphine:Buprenorphine:

• Introduction:• developed in 1970• Agonist-antagonist( or partial agonist)?

analgesic.• Low dependency• Substitution of heroin and morphine with lower

withdrawal symptoms• Significant drug of abuse (IV injection form)• Favorable for detoxification and maintenance

therapy

Pharmacology and Pharmacology and pharmacokinetics pharmacokinetics

• HL: 48-72 hours.• Partial µ agonist (pure agonist in lower doses)• Weak Ќ antagonist (agonist-antagonist in higher doses)• Safe and little chance of lethal doses• Ceiling effect and safety:=8-12 mg →maximum clinical effect=↑8-12mg(16-32mg) →:-no increase of clinical effect and side effect-increase duration of clinical effect (suitable for

maintenance therapy)

Drug formsDrug forms

• Solution: buprenorphine + alcohol• Tablet:( 2 & 8mg) buprenorphine only (subutex)• Tablet:(2 & 8mg) buprenorphine + naloxone

(4/1) (subuxone)…superiority?• Injection form?• 4 mg of sublingual tablet=40 mg methadone• 8 mg of sublingual tablet=50-60 mg methadone

Protocol: outpatient Setting Protocol: outpatient Setting ProtocolProtocol

• Initial dose:2-8 mg( first dose withdrawal)

• Stabilization of patient next days(2-4mg/day up to 8-32mg)

• Stabilization for 24-48 hours( or more)

• Decreasing 2mg of drug/ days- week.

Protocol: Inpatient Setting Protocol: Inpatient Setting

8mg of Buprenorphine on the first 8mg of Buprenorphine on the first day and 2mg/day reduction on the day and 2mg/day reduction on the

next days. next days.

TramadolTramadol

• Mechanism: serotonin & nor-epinphrin reuptake inhibitor(Parent compound) + µ agonist(metabolize compound-desmethyltramadol).

• Withdrawal control with200-400mg for modest and 600 mg for sever withdrawal)

• Seizure in high doses CNS suppressant Using with B.Z & seretonergic syndrome with SSRI.

αα2 Agonists2 Agonists

2

- Clonidine

-Lofexidine (Less Hypotensive)

2

Mechanism & SideffectsMechanism & Sideffects

• It has specificity towards the presynaptic alpha-2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone

• This drug may cause drowsiness, lightheadedness, dry mouth, dizziness, or constipation. Clonidine may also cause hypotension. It can also cause inhibition of orgasm in women

ClonidineClonidine

• Patient stabilized on low dose of opioids (30 – 40 Methadone/ day).

• starting dose 0/1 – 0/3.

*Maximum dose (1/mg/day) In outpatient & 1.5-2.0mg/day In hospitalized patients.

*Adjusting Dose based On Hypotension & sedation.

Contraindication: acute or chronic cardiac disease, Renal & metabolic disease, Hypotension).

Clonidine Clonidine • More effective in: =stabilization on Methadone. =good Relationship with therapist.• Effective in suppressing of : Sweating, cramps,

nusea, vomiting and diarrhea• Ineffective In suppressing of (Muscle aches –

Lethargy – Insomnia – restlessness and Craving).• Non – effective on relapse after complete

detoxification.• Facilitation of detoxification of Methadone

Maintained patients & subsequent stabilization on naltrexone.

• Escitalopram is associated with reductions in pain severity and pain interference in opioid dependent patients with depressive symptoms

Rapid & Ultrarapid detoxification Rapid & Ultrarapid detoxification

• Naloxone + clonidine

• Naloxone + clonidine + sedatives

• Naltrexon + clonidine and/ or sedatives

• Full Anesthesia For 3-4 hours.

other techniquesother techniques

* Symptomatic treatments (Healthy & Motivated).

• Abrupt withdrawal withought Intervention.

* Abrupt withdrawal with Emotional support

• Acupuncture

• Herbal Medication

Opioid Dependence Treatment in Opioid Dependence Treatment in Special PopulationsSpecial Populations

• Criminal Justice Patients

• Pregnant Women

• Health professionals • Psychiatric Patients

• HIV-positives & hepatitis-c positives

Opioid Dependence Treatment in Opioid Dependence Treatment in Special PopulationsSpecial Populations

=Criminal Justice Patients

*Opium use and criminal activity:

-This relation is complex and reciprocal.

-There is no direct relation between opioid use and criminal behavior( except in withdrawal periods for ……... ) .

*Opium dependents in justice system:

-Direct coercion to treatment

-Incarceration and opium dependence

Opioid Dependence Treatment in Opioid Dependence Treatment in Special PopulationsSpecial Populations

=Pregnant Women:• Poor prenatal care• Low birth weight • Elevated risk of morbidity & mortality• No teratogenicity reported • Cautious detoxification( before 14 & after 32 weeks)• Methadone in pregnancy( dose adjustment).• Buprenorphine in pregnancy.

• Health professionals:

Opioid Dependence Treatment in Opioid Dependence Treatment in Psychiatric PatientsPsychiatric Patients

=Mood Disorders: -Mood disorders as most prevalent disorders among opium

dependence. -Routine Vs selected antidepressant administration. -Opium treatment program and control of depressive symptoms.

= Bipolar Disorder and opium dependence: -Management principles………………….. - Drug interactions( carbamazepine & methadone). -MMT & Bipolar Disorder.

=Anxiety Disorders: comorbidity and principles of drug treatments.

Opioid Dependence Treatment in Opioid Dependence Treatment in Psychiatric PatientsPsychiatric Patients

=Psychotic Disorders:-comorbidity of psychotic disorders and opium dependence- Antimanic & antipsychotic effects of opioids (Methadone)

=Alcohol Abuse:-Comorbidity of Opioid and alcohol abuse( up to 50%)-Balance of Alcohol & Opioid use-Disulfiram & Methadone-naltreoxone with dual benefits.=Nicotine dependence in opium users

=Polysubstance abuse:-more psycopathology than single users and poor outcme-more suitable for maintenance program-more suitable for TC or NA groups

Hiv positvesHiv positves

• Only 33% of study participants received concurrent treatment for MI and SA,

• CONCLUSION: Among adults with HIV/AIDS and co-occurring MH and SA disorders, utilization of MH and SA services needs to be improved. 

• The available evidence strongly suggests the need for the large-scale implementation of comprehensive treatment and care strategies for IDUs that include both treatment of drug dependence and HAART.

• highly active antiretroviral treatment (HAART).• injecting drug users (IDUs)•  Improving treatment adherence in drug abusers who are

HIV-positive.