Internet Mental Health
 
OPIOID USE DISORDER
 


Prediction: Chronic for years or decades

      Occupational-Economic:
  • Works poorly with others (work absenteeism)
  • Lacks full-time employment
  • Requires financial assistance (poverty)
  • Impaired cognitive functioning (concentration, memory, motivation)
      Social:
  • Detachment (suspiciousness, social withdrawal)
  • Antagonism (hostility, crime) theft, prostitution, drug-dealing
  • Disinhibition (irresponsibility, impulsivity, dangerous risk taking) high risk of divorce and child abuse/neglect
      Medical:
  • Denial of addiction; tuberculosis; sexual dysfunction; high death rate (overdose; illness; accidental injury; suicide); needle users get viral infections (90% get hepatitis C, 10%-60% get HIV) and bacterial infections (cellulitis, endocarditis)


Explanation Of Symbols

Quality of Life Problems for Opioid Use Disorder


(Personal Note: One of my patients died of an accidental heroin overdose. She had been off heroin for a year, then relapsed and immediately returned to her former high dose of heroin. However, during her drug-free year, she had lost her tolerance to heroin. Thus returning to a high dose of heroin proved fatal on the first injection. In America, the majority of drug intoxication deaths are due to opioids, and recently there has been a significant increase in opioid deaths.)

SYNOPSIS

Dependence Syndrome Due To Use Of Opioids F12 - ICD10 Description, World Health Organization
Repeated use of opioids that typically includes a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state.
Opioid Use Disorder - Diagnostic Criteria, American Psychiatric Association

An individual diagnosed with opioid use disorder needs to meet all of the following criteria:

  • A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

    • Opioids are often taken in larger amounts or over a longer period than was intended.

    • There is a persistent desire or unsuccessful efforts to cut down or control opioid use.

    • A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.

    • Craving, or a strong desire or urge to use opioids.

    • Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.

    • Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.

    • Important social, occupational, or recreational activities are given up or reduced because of opioid use.

    • Recurrent opioid use in situations in which it is physically hazardous.

    • Opioid use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.

    • Tolerance, as defined by either of the following:

      • A need for markedly increased amounts of opioids to achieve intoxication or desired effect.

      • A markedly diminished effect with continued use of the same amount of an opioid.

    • Withdrawal, as manifested by either of the following:

      • The characteristic opioid withdrawal syndrome:

        • Presence of either of the following:

          • Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e., several weeks or longer).

          • Administration of an opioid antagonist after a period of opioid use.

        • Three (or more) of the following developing within a minutes to several days after the cessation of (or reduction in) opioid use:

          • Dysphoric mood.

          • Nausea or vomiting.

          • Muscle aches.

          • Lacrimation or rhinorrhea.

          • Pupillary dilation, piloerection, or sweating.

          • Diarrhea.

          • Yawning.

          • Fever.

          • Insomnia.

      • Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.

  • Specify if:

    • In early remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met for at least 3 months but for less than 12 months (with the exception that the criterion, "Craving, or a strong desire or urge to use opioid," may be met).

    • In sustained remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met at any time during a period of 12 months or longer (with the exception that the criterion, "Craving, or a strong desire or urge to use opioid," may be met).

  • Specify if:

    • On maintenance therapy: The individual is taking a prescribed agonist medication, such as methadone or buprenorphine and none of the criteria for opioid use disorder have been met for that class of medication (except tolerance to, or withdrawal from, the agonist). This category also applies to those individuals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist such as oral naltrexone or depot naltrexone.

    • In a controlled environment: This additional specifier is used if the individual is in an environment where access to opioids is restricted.

Opioid dependence is compulsive use of an opioid drug, leading to clinically significant impairment or distress. Commonly abused opioids include codeine, fentanyl, heroin, morphine, opium, methadone, oxycodone, and hydrocodone. The physical signs of opioid intoxication are: drowsiness, slurred speech, pupillary constriction, and decreased level of consciousness. Severe opioid intoxication causes: respiratory depression, hypotension, and hypothermia. The psychological symptoms of opioid intoxication are: apathy, sedation, disinhibition, psychomotor retardation, impaired attention, impaired judgment, and impaired personal functioning. Opioid dependence can cause: delirium, psychosis, depression, sexual impairment and sleep disorder.

Effective Therapies

After brief detoxification, more than two-thirds of opioid-addicts quickly relapse unless they receive years of treatment with a long-acting opioid blocker (naltrexone implants or injectable extended-release naltrexone) plus psychosocial treatment. To maintain their abstinence, it is essential that recovering addicts: (1) not associate with active alcohol or drug abusers, (2) not use alcohol or any illicit drug, and (3) avoid alcohol or drug-using environments.

Ineffective Therapies

There is inadequate evidence available to prove the effectiveness of psychosocial interventions alone for the treatment of opiate use disorders or that they are superior to any other type of treatment.

Maintenance therapy with methadone, buprenorphine or heroin is effective in retaining patients in treatment and suppressing heroin use but, on average, does not decrease criminal behavior or decrease the high mortality rate associated with opioid addiction. However, for severely heroin-addicted patients, mandatory treatment in a coercive residential setting with methadone maintenance can be life-saving. In America, the majority of drug intoxication deaths are due to opioids, and recently there has been a significant increase in opioid deaths. In Spain, the average heroin-addicted patient on methadone maintenance therapy died at age 39. Thus these heroin-addicted, methadone maintenance patients lost, on average, 38 years of life. Many heroin-addicted individuals abuse alcohol, cocaine and methamphetamine. Thus methadone maintenance therapy for their heroin addiction is, at best, only a partial treatment for their many addictions. This is why legalization of these highly addictive and lethal opioids would be a public health disaster.

Legalizing Illicit Drugs

Some people argue that illicit drugs should be legalized to decrease the crime associated with these drugs. Historically, tobacco and alcohol were once illegal drugs. Tobacco smoking is now the leading cause of death in America, and alcoholism is the third leading cause of death. Thus legalizing illicit drugs does not make them any less medically and socially harmful. In fact the opposite is true; legalizing illicit drugs increases their use and the harm they cause.

Top 20 Most Harmful Drugs In Britain In 2008

Professor David Nutt published in the Lancet the following rating of Britain's most dangerous drugs. They are listed in descending order from the most harmful.

1. Heroin

Class A drug. Originally used as a painkiller and derived from the opium poppy. There were 897 deaths recorded from heroin and morphine use in 2008 in England and Wales, according to the Office of National Statistics (ONS). There were around 13,000 seizures, amounting to 1.6m tonnes of heroin.

2. Cocaine

Class A. Stimulant produced from the South American coca leaf. Accounted for 235 deaths -- a sharp rise on the previous year's fatalities. Nearly 25,000 seizures were made, amounting to 2.9 tonnes of the drug.

3. Barbituates

Class B. Synthetic sedatives used for anaesthetic purposes. Blamed for 13 deaths.

4. Street methadone

Class A. A synthetic opioid, commonly used as a substitute for treating heroin patients. Accounted for 378 deaths and there were more than 1,000 seizures of the drug.

5. Alcohol

Subject to increasing concern from the medical profession about its damage to health. According to the ONS, there were 8,724 alcohol deaths in the UK in 2007. Other sources claim the true figure is far higher.

6. Ketamine

Class C. A hallucinogenic dance drug for clubbers. There were 23 ketamine-related deaths in the UK between 1993 and 2006. Last year there were 1,266 seizures.

7. Benzodiazepines

Class C. A hypnotic relaxant used to treat anxiety and insomnia. Includes drugs such as diazepam, temazepam and nitrazepam. Caused 230 deaths and 1.8m doses were confiscated in more than 4,000 seizure operations.

8. Amphetamine

Class B. A psychostimulant that combats fatigue and suppresses hunger. Associated with 99 deaths, although this tally includes some ecstasy deaths. Nearly 8,000 seizures, adding up to almost three tonnes of confiscated amphetamines.

9. Tobacco

A stimulant that is highly addictive due to its nicotine content. More than 100,000 people a year die from smoking and tobacco-related diseases, including cancer, respiratory diseases and heart disease.

10. Buprenorphine

An opiate used for pain control, and sometimes as a substitute to wean addicts off heroin. Said to have caused 43 deaths in the UK between 1980 and 2002.

11. Cannabis

Class B. A psychoactive drug recently appearing in stronger forms such as "skunk". [Since this video was made; there is now conclusive proof that cannabis causes a 6.7 fold increase in the risk of developing schizophrenia.] Caused 19 deaths and there were 186,000 seizures, netting 65 tonnes of the drug and 640,000 cannabis plants.

12. Solvents

Fumes inhaled to produce a sense of intoxication. Usually abused by teenagers. Derived from commonly available products such as glue and aerosol sprays. Causes around 50 deaths a year.

13. 4-MTA

Class A. Originally designed for laboratory research. Releases serotonin in the body. Only four deaths reported in the UK between 1997 and 2004.

14. LSD

Class A. Hallucinogenic drug originally synthesised by a German chemist in 1938. Very few deaths recorded.

15. Methylphenidate

Class B drug. Brand name of Ritalin. A psychostimulant sometimes used in the treatment of attention deficit disorders.

16. Anabolic steroids

Class C. Used to develop muscles, notably in competitive sports. Also alleged to induce aggression. Have been blamed for causing deaths among bodybuilders. More than 800 seizures.

17. GHB

Class C drug. A clear liquid dance drug said to induce euphoria, also described as a date rape drug. Can trigger comas and suppress breathing. Caused 20 deaths and 47 seizures were recorded.

18. Ecstasy

Class A. Psychoactive dance drug. Caused 44 deaths, with around 5,000 seizures made.

19. Alykl nitrites

Known as "poppers". Inhaled for their role as a muscle relaxant and supposed sexual stimulant. Reduce blood pressure, which can cause fainting and in some cases death.

20. Khat

A psychoactive plant, the leaves of which are chewed in east Africa and Yemen. Also known as qat. Produces mild psychological dependence. Its derivatives, cathinone and cathine, are Class C drugs in the UK.

Description

Neuroscientist, Dr. Marc Lewis, Tells Of His Own Addiction And Cure

Stories

Diagnosis

Rating Scales

Treatment

Pharmacological Detoxification Interventions

  • RESEARCH SUMMARY:
      FINDINGS:
      Opioid Dependence is chronic, episodic illness which requires more than brief hospital or residential care. During detoxification, a combination of pharmaceutical detoxification treatment plus psychosocial treatment is more effective than pharmaceutical detoxification treatment alone. The best detoxification treatment is to use an initial 2-4 mg dose of buprenorphine combined with clonidine, other ancillary medications, and progressively increasing doses of oral naltrexone over 3-5 days up to the target dose of naltrexone.

      CONCLUSION:
      After brief detoxification, more than two-thirds of opioid-addicts quickly relapse unless they receive years of treatment with a long-acting opioid blocker (naltrexone) plus psychosocial treatment. To maintain their abstinence, it is essential that recovering addicts: (1) not associate with active alcohol or drug abusers, (2) not use alcohol or any illicit drug, and (3) avoid alcohol or drug-using environments.

  • Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. (2012) DESIGN: Cochrane literature review. CONCLUSIONS: Among the current detoxification regimens, the available clinical and scientific data suggest that the best approach may be using an initial 2-4 mg dose of buprenorphine combined with clonidine, other ancillary medications, and progressively increasing doses of oral naltrexone over 3-5 days up to the target dose of naltrexone.
  • Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. (2011) DESIGN: Cochrane literature review. SUBJECTS: FINDINGS: Compared to any pharmacological treatment alone, the association of any psychosocial with any pharmacological was shown to significantly reduce dropouts (RR 0.71), use of opiate during the treatment (RR 0.82), use of opiate at follow up (RR 0.66), and clinical absences during the treatment (RR 0.48). Moreover, with the evidence currently available, there are no data supporting a single psychosocial approach. CONCLUSIONS: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, participants abstinent at follow-up and clinical attendance.
  • Transitioning opioid-dependent patients from detoxification to long-term treatment: efficacy of intensive role induction. (2011) DESIGN: 30-day, openly assigned, randomised trial. SUBJECTS: 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. CONCLUSIONS: The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.
  • The potential risks and high cost of using opioid blocking drugs during heavy sedation or anaesthesia to bring on withdrawal outweigh the benefits (2010) DESIGN: Cochrane literature review. SUBJECTS: Nine studies involving 1109 patients. CONCLUSIONS: Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.
  • Alpha2-adrenergic agonists for the management of opioid withdrawal. (2009) DESIGN: Cochrane literature review. SUBJECTS: Twenty-four studies, involving 1631 patients. CONCLUSIONS: Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. No significant difference in efficacy was detected for treatment regimes based on clonidine or lofexidine, and those based on reducing doses of methadone over a period of around 10 days but methadone is associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.
  • Buprenorphine for the management of opioid withdrawal. (2009) DESIGN: Cochrane literature review. SUBJECTS: Twenty-two studies involving 1736 patients. CONCLUSIONS: Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal.
  • Post-treatment outcomes of buprenorphine detoxification in community settings: a systematic review. (2008) DESIGN: Literature review. SUBJECTS: 5 studies. FINDINGS: Detoxification completion rates were 65-100%, but relatively few treatment completers were then drug free at their follow-up appointments. In subsequent prescribing, more patients had returned to opioid maintenance than complied with naltrexone. CONCLUSIONS: Buprenorphine is a suitable medication for the process of opiate detoxification but that this newer treatment option has not led to higher rates of abstinence following withdrawal.
  • Using buprenorphine to facilitate entry into residential therapeutic community rehabilitation. (2007) DESIGN: Retrospective observational cohort study. SUBJECTS: 38 opioid-dependent patients entering a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community program. FINDINGS: 89% of patients completed a 14-day buprenorphine taper protocol, 50% completed an initial 3- to 4-week stay, and 39% completed at least 3 months of residential treatment at the therapeutic community. Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. CONCLUSIONS: A 14-day buprenorphine-naloxone (Suboxone) detoxification can improve the viability of long-term residential treatment for managing opioid dependence.
  • Outpatient treatment engagement and abstinence rates following inpatient opioid detoxification. (2006) DESIGN: Retrospective cohort analysis. SUBJECTS: 112 male veterans referred to drug-free outpatient treatment following inpatient detoxification. FINDINGS: Most patients (78%) successfully completed acute detoxification, 49% initiated oral naltrexone, and 76% accepted a VA aftercare plan. At 90-day follow-up, only 22% remained in aftercare, and < 3% had toxicology-verified abstinence from opioids. At one-year follow-up, 1 out of 5 had been readmitted for detoxification and 4.5% had died. CONCLUSIONS: Most patients successfully detoxified from opioids, but very few remained engaged and stabilized in abstinence-oriented outpatient treatment.
  • Methadone at tapered doses for the management of opioid withdrawal. (2005) DESIGN: Cochrane literature review. SUBJECTS: Sixteen trials involving 1187 patients. FINDINGS: Comparing methadone versus any other pharmacological treatment (adrenergic agonists, other opioid agonists, or chlordiazepoxide) we observed no clinical difference between the two treatments in terms of completion of treatment. CONCLUSIONS: Slow tapering with temporary substitution of long acting opioids can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use.
  • Inpatient opiate detoxification in Geneva: follow-up at 1 and 6 months. (2000) DESIGN: Retrospective observational study. SUBJECTS: 73 patients admitted for 15-day inpatient detoxification using methadone tapering. FINDINGS: After 1 month, 65% of the patients were using drugs (half of them were dependent again, half of them had used occasionally) and 35% were completely abstinent. After 6 months, 50% were physically dependent again, 13% had lapsed occasionally, 37% were abstinent. Factors associated with treatment failure were: cocaine abuse, presence of legal problems, and short duration of hospital stay. CONCLUSIONS: Six months after 15-day inpatient detoxification, without followup pharmacotherapy, the majority of patients relapsed to heroin use.

Opioid Antagonist Maintenance Therapy With Naltrexone Implants (That Last 6 Months) Or Extended-Release Naltrexone Injections (That Last 1 Month)

  • RESEARCH SUMMARY:
      FINDINGS:
      • NALTREXONE IMPLANTS: After 6 months of treatment, 53% of opioid-addicted patients on naltrexone implant treatment remained in treatment without relapse compared with only 11% on placebo. After 6 months, 44% of opioid-addicted patients on naltrexone implant treatment were abstinent from opioids. Mean opioid use was reduced from 18 days during the month preceding treatment to 6 days after 6 months. The 3-year mortality rates of patients on naltrexone implant treatment are similar to those of methadone maintenance treatment. Long-acting naltrexone implants appear to block all opiates and lack hepatotoxicity. Of the patients who received the first naltrexone implant, only 51% accepted a second naltrexone implant. Naltrexone implant therapy patients, compared to buprenorphine, had significantly longer days in treatment per episode (238 days vs. 47), and longer total treatment duration (371 days vs. 162).

      • NALTREXONE EXTENDED-RELEASE INJECTIONS: Over 24-weeks of treatment, opioid-addicted patients on injectable extended-release naltrexone remained abstinent for 90% of the time compared with 35% of the time for the placebo group. Total healthcare costs for patients given injectable extended-release naltrexone were 49% lower than those for methadone.

      CONCLUSION:
      In opioid dependence, following detoxification, naltrexone implants and injectable extended-release naltrexone show efficacy for maintaining abstinence, improving retention, decreasing craving, and preventing relapse. . After 6 months, long-acting naltrexone implants can prevent opiate overdose for several additional months.
  • Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. (2012) DESIGN: Six-month double-blind, placebo-controlled, randomized trial. SUBJECTS: 306 opioid-addicted patients recently undergoing detoxification. FINDINGS: By month 6, 52.9% patients in the naltrexone implant + oral placebo (NI+OP) group remained in treatment without relapse compared with 15.7% patients in the placebo implant + oral naltrexone (PI+ON ) group and 10.8% patients in the placebo implant + oral placebo (PI+OP) group. The proportion of urine screening tests yielding negative results for opiates was 63.6% for the NI+OP group; 42.7% for the PI+ON group; and 34.1% for the PI+OP group. CONCLUSIONS: The naltrexone implant is more effective than oral naltrexone or placebo.
  • Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. (2011) DESIGN: 24-week, double-blind, placebo-controlled, randomised trial. SUBJECTS: 250 opioid-addicted patients recently undergoing detoxification. FINDINGS: The median proportion of weeks of confirmed abstinence was 900% in the injectable extended-release naltrexone (XR-NTX) group compared with 350% in the placebo group. Median retention was over 168 days in the injectable extended-release naltrexone group compared with 96 days in the placebo group. No injectable extended-release naltrexone (XR-NTX) patients died, overdosed, or discontinued owing to severe adverse events. CONCLUSIONS: The injectable extended-release naltrexone (XR-NTX) is more effective than placebo and is very safe.
  • Cost and utilization outcomes of opioid-dependence treatments. (2011) DESIGN: Retrospective claims database analysis. SUBJECTS: 13,316 patients. FINDINGS: Patients given injectable extended-release naltrexone (XR-NTX) had fewer opioid-related and non-opioid-related hospitalizations than patients receiving oral medications. Despite higher costs for XR-NTX, total healthcare costs were not significantly different from those for oral naltrexone or buprenorphine, and were 49% lower than those for methadone. CONCLUSIONS: Patients with opioid dependence who received medication for this disorder had lower hospital utilization and total costs than patients who did not receive pharmacologic therapy. Patients who received extended-release naltrexone (NTX-XR) had lower inpatient healthcare utilization at comparable or lower total costs than those receiving oral medications.
  • Intramuscular extended-release naltrexone: current evidence. (2011) DESIGN: Literature Review. CONCLUSIONS: Injectable extended-release naltrexone (XR-NTX; Vivitrol) safety and tolerability is good, without adverse hepatic impact. Injectable extended-release naltrexone (XR-NTX) use results in cost savings and decreased intensive service utilization relative to oral agents like methadone. In opioid dependence, following detoxification, injectable extended-release naltrexone shows efficacy for maintaining abstinence, improving retention, decreasing craving, and preventing relapse.
  • Recent developments in naltrexone implants and depot injections for opiate abuse: the new kid on the block is approaching adulthood. (2010) DESIGN: Literature Review. CONCLUSIONS: Long-acting naltrexone implants can deliver relapse-preventing serum naltrexone levels for around six months per implant. Naltrexone implants have proven superior to oral naltrexone and placebo implants, or with standard post-detoxification care. After 6 months, long-acting naltrexone implants can prevent opiate overdose for several additional months. The 3-year mortality rates are similar to those of methadone maintenance treatment. Long-acting naltrexone implants appear to block all opiates and lacks hepatotoxicity. Therapy with long-acting naltrexone implants should last for at least 18 months.
  • Challenges to antagonist blockade during sustained-release naltrexone treatment. (2010) DESIGN: Retrospective case file audit over a 6-month period. SUBJECTS: 60 opioid-dependent patients receiving treatment with naltrexone implants. FINDINGS: After 6 months, 44% were abstinent from opioids. Mean opioid use was reduced from 18 days during the month preceding treatment to 6 days after 6 months. Opioid use was associated with use of non-opioid drugs and criminal behaviour. CONCLUSIONS: Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly.
  • Retention in naltrexone implant treatment for opioid dependence. (2010) DESIGN: Retrospective case file audit. SUBJECTS: 61 patients were offered a second naltrexone implant after 6 months. FINDINGS: Of the patients who received the first naltrexone implant, 51% accepted a second naltrexone implant. Higher levels of substance misuse and criminal activity during naltrexone treatment were negatively related to subsequent retention. CONCLUSIONS: Rates of retention among opioid-dependent patients receiving naltrexone implant treatment are encouraging and support this as a feasible long-term treatment option.
  • Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial. (2009) DESIGN: 6-month, openly assigned, randomised trial. SUBJECTS: 56 abstinence-oriented patients who completed in-patient treatment for opioid dependence were randomly and openly assigned to receive either a 6-month naltrexone implant or their usual aftercare. FINDINGS: Patients receiving naltrexone implants had on average 45 days less heroin use and 60 days less opioid use than controls in the 180-day period. CONCLUSIONS: Naltrexone implant treatment safely and significantly reduces opioid use in a motivated population of patients.
  • Comparative treatment and mortality correlates and adverse event profile of implant naltrexone and sublingual buprenorphine. (2009) DESIGN: Retrospective registry database analysis. SUBJECTS: 255 naltrexone implant therapy and 2,518 buprenorphine patients were followed for 1,322 and 8,030 patient-years, respectively. FINDINGS: Naltrexone implant therapy patients, compared to buprenorphine, had significantly longer days in treatment per episode (238 days vs. 47), and longer total treatment duration (371 days vs. 162). CONCLUSIONS: Naltrexone implant therapy economizes treatment resources without compromising safety concerns.
  • Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone. (2008) DESIGN: Single case report of 17-year-old opioid-addicted female going into painful opioid withdrawal after using oxycodone at the end of her 3rd monthly injection of extended release naltrexone (Vivitrol). CONCLUSIONS: This case suggests that the opioid blockade may be overcome when naltrexone levels drop towards the end of the dosing interval, producing vulnerability to subsequent naltrexone-induced withdrawal.
  • Unplanned admissions to two Sydney public hospitals after naltrexone implants. (2008) DESIGN: Retrospective case file audit over a 12-month period. SUBJECTS: Twelve cases were identified: eight were definitely or probably related to naltrexone implants or the implantation procedure (rapid detoxification). FINDINGS: Six patients had severe opiate withdrawal and dehydration, with an average hospital stay of 2.3 days. One patient had an infection at the implant site, and one an underlying anxiety disorder requiring psychiatric admission. Three patients had analgesia complications, and one had unrelated cardiac arrhythmia. CONCLUSIONS: Naltrexone implants require careful case selection and clinical management.

Opioid Antagonist Maintenance Therapy With Oral Naltrexone

  • Oral naltrexone maintenance treatment for opioid dependence. (2011) DESIGN: Cochrane literature review. SUBJECTS: Thirteen studies, 1158 patients. FINDINGS: Comparing naltrexone versus placebo or no pharmacological treatments, no statistically significant difference were noted for all the primary outcomes considered. CONCLUSIONS: Maintenance therapy with oral naltrexone cannot yet be considered a treatment which has been scientifically proven.

Opioid Agonist Maintenance Therapy With Methadone, Buprenorphine Or Heroin

  • RESEARCH SUMMARY:
      FINDINGS:
      Maintenance therapy with methadone, buprenorphine or heroin for opioid dependence increases the retention of patients in treatment when compared to non-pharmacological treatments. Buprenorphine has a higher rate of retention of patients than methadone. There is only weak evidence that these opioid agonists decrease criminal activity or mortality. Treatment with these opioid agonists suffers from a high drop-out rate (half of patients are still in therapy after 3 years). These opioid agonists (especially methadone and heroin) are very addictive and prone to overdose. Treatment with these opioid agonists does not improve the opioid-addict's mental health or quality of life. Most opioid addicts are also addicted to alcohol or other illicit drugs. Personality disorders play a major role in heroin addiction; 72% of heroin addicts have antisocial personality disorder and 47% have borderline personality disorder. Treatment with methadone, buprenorphine or heroin does nothing to combat these other addictions or personality disorders.

      CONCLUSION:
      Maintenance therapy with methadone, buprenorphine or heroin is the most effective in retaining patients in treatment and suppressing heroin use but shows weak evidence of effectiveness toward other relevant outcomes.

  • Heroin maintenance for chronic heroin-dependent individuals. (2011) DESIGN: Cochrane literature review. SUBJECTS: Eight studies involving 2007 patients. FINDINGS: Five studies compared supervised injected heroin plus flexible dosages of methadone treatment to oral methadone only and showed that heroin helps patients to remain in treatment (RR 1.44), and to reduce use of illicit drugs. Maintenance with supervised injected heroin does NOT have a protective effect on mortality. Heroin provision can reduce criminal activity and incarceration/imprisonment. Social functioning improved in all the intervention groups with heroin groups having slightly better results. CONCLUSIONS: Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed other maintenance treatments, and it should be provided in clinical settings where proper follow-up is ensured.
  • Maintenance agonist treatments for opiate dependent pregnant women. (2011) DESIGN: Cochrane literature review. SUBJECTS: Three trials with 96 pregnant women. FINDINGS: There was no difference in drop out rate and use of primary substance between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin. CONCLUSIONS: We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another.
  • The evidence doesn't justify steps by state Medicaid programs to restrict opioid addiction treatment with buprenorphine. (2011) DESIGN: Retrospective claims database analysis. SUBJECTS: 33,923 Massachusetts opioid-addicted Medicaid beneficiaries receiving either buprenorphine, methadone, drug-free treatment, or no treatment. FINDINGS: Buprenorphine appears to have significantly expanded access to treatment because the drug can be prescribed by a physician and taken at home compared with methadone, which by law must be administered at an approved clinic. Buprenorphine was associated with more relapse-related services but $1,330 lower mean annual spending than methadone when used for maintenance treatment. Mortality rates were similar for buprenorphine and methadone. By contrast, mortality rates were 75 percent higher among those receiving drug-free treatment, and more than twice as high among those receiving no treatment, compared to those receiving buprenorphine. CONCLUSIONS: The evidence does not support rationing buprenorphine to save money or ensure safety.
  • Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. (2009) DESIGN: Cochrane literature review. SUBJECTS: Eleven studies with 1969 patients. FINDINGS: Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (RR = 0.66), but not statistically different in criminal activity or mortality. CONCLUSIONS: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. Methadone does not show a statistically significant superior effect on criminal activity or mortality.
  • Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial. (2009) DESIGN: Randomized clinical trail. SUBJECTS: 116 heroin-dependent inmates who volunteered to be randomly allocated to either buprenorphine or methadone maintenance before release from jail. FINDINGS: Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%). Buprenorphine patients were less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%). CONCLUSIONS: After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance.
  • Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients. (2008) DESIGN: 12-Month prospective-longitudinal naturalistic study. SUBJECTS: 2694 patients. FINDINGS: The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. CONCLUSIONS: The study underlines the overall 12-month effectiveness of various forms of agonist maintenance. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life.
  • Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. (2008) DESIGN: Cochrane literature review. SUBJECTS: Twenty four studies with 4497 patients. CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivered at adequate dosages.
  • Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. (2007) DESIGN: Literature review. CONCLUSIONS: Both flexible-dose methadone maintenance therapy and buprenorphine maintenance therapy are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with methadone maintenance therapy was found be somewhat more effective in maintaining individuals in treatment than flexible-dose buprenorphine maintenance therapy and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the the possible risk of higher mortality of methadone maintenance therapy.
  • The costs and consequences of three policy options for reducing heroin dependency. (2007) DESIGN: Retrospective Australian database analysis. CONCLUSIONS: If the post-programme abstinence rates are sustained for 2 years, then for an average heroin user the cost of averting a year of heroin use is approximately AUD$5000 for pharmacotherapy maintenance, AUD$11,000 for residential rehabilitation and AUD$52 000 for prison. If the completion rate in pharmacotherapy maintenance was raised above 95% (by the threat of prison for non-completers), the combined model of treatment plus prison may become the most cost-effective option.
  • A randomized controlled trial of interim methadone maintenance. (2006) DESIGN: Randomized, controlled, clinical trial. SUBJECTS: 319 opioid-addicted patients awaiting methadone maintenance therapy. FINDINGS: Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%). CONCLUSIONS: Rapid access to methadone improved entry and outcomes in heroin addicts awaiting methadone treatment.
  • One year outcomes for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS). (2006) DESIGN: Longitudinal prospective cohort study. SUBJECTS: 745 individuals entering treatment (methadone/buprenorphine maintenance therapy; detoxification; residential rehabilitation) and 80 heroin users not seeking treatment. FINDINGS: 80% of the original sample were re-interviewed at 1 year. The majority of those who had entered treatment were heroin abstinent at 1 year (maintenance therapy 65%, detoxification 52%, residential rehabilitation 63%) compared to 25% of the non-treatment sample. The reduction in heroin use among the treatment samples was paralleled by reductions in poly drug use. There were also substantial reductions in risk-taking, crime and injection-related health problems across all treatment groups, and less marked reductions among the non-treatment group. Psychopathology was dramatically reduced among the treatment modalities, while remaining stable among the non-treatment group. CONCLUSIONS: At 1 year, there were impressive reductions in drug use, criminality, psychopathology and injection-related health problems following treatment exposure. The positive findings were associated with a greater "dose" of treatment, and with more treatment stability over the follow-up period.
  • Reductions in heroin use are not associated with increases in other drug use: 2-year findings from the Australian Treatment Outcome Study. (2006) DESIGN: Longitudinal prospective cohort study. SUBJECTS: 615 Australian opioid-addicts in treatment. FINDINGS: At 2-year followup, heroin use had significantly decreased. CONCLUSIONS: There was no evidence for drug substitution in the face of reduced heroin use in this cohort of treatment seekers.
  • Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial. (2006) DESIGN: Open-label randomized controlled study. SUBJECTS: 235 opioid-addicts. FINDINGS: No significant difference in outcomes was found between randomized groups over time. CONCLUSIONS: Dihydrocodeine is a viable alternative to methadone as a maintenance treatment for opiate dependence.
  • The characteristics of heroin users entering treatment: findings from the Australian treatment outcome study (ATOS). (2005) DESIGN: Longitudinal prospective cohort study. SUBJECTS: 745 individuals entering treatment (methadone/buprenorphine maintenance therapy; detoxification; residential rehabilitation) and 80 heroin users not seeking treatment. FINDINGS: The majority of the sample (55%) were criminally active in the month preceding interview. Injection-related health problems (74%) and a history of heroin overdose (58%) were commonly reported. There were high degrees of psychiatric co-morbidity, with 49% reporting severe psychological distress, 28% having current major depression, 37% having attempted suicide and 42% having a lifetime history of post-traumatic stress disorder. Personality disorders were also prevalent, with 72% meeting criteria for antisocial personality disorder and 47% screening positive for borderline personality disorder.
  • A randomised trial of the cost effectiveness of buprenorphine as an alternative to methadone maintenance treatment for heroin dependence in a primary care setting. (2005) DESIGN: Randomised, open-label, 12-month trial. SUBJECTS: 139 heroin-dependent outpatients. FINDINGS: The estimated mean number of heroin-free days did not differ significantly between those randomised to methadone (225 days), or buprenorphine (222 days) over the year of the trial. CONCLUSIONS: The trial found no significant differences in costs or outcomes between methadone and buprenorphine maintenance.
  • An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. (2005) DESIGN: Literature review. SUBJECTS: 52 studies with 12,075 participants. Methadone maintenance treatment (MMT) was compared with methadone detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT). FINDINGS: Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin: MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were available for mortality and criminal activity.. CONCLUSIONS: These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes.
  • Methadone maintenance at different dosages for opioid dependence. (2003) DESIGN: Cochrane literature review. SUBJECTS: 22 studies with 5994 patients. CONCLUSIONS: Methadone dosages ranging from 60 to 100 mg/day are more effective than lower dosages in retaining patients and in reducing use of heroin and cocaine during treatment.
  • Safety of injectable opioid maintenance treatment for heroin dependence. (2003) DESIGN: Randomized, double-blind, placebo-controlled trail. SUBJECTS: 25 opioid-dependent patients on intravenous (IV) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo. FINDINGS: After heroin injection, marked respiratory depression progressing to a Cheyne-Stokes pattern occurred. Peripheral arterial blood oxygenation decreased to 78.9%. During hypoxia, 7 of the 16 subjects experienced intermittent and somewhat severe bradycardia. Five subjects exhibited paroxysmal EEG patterns. After methadone injection, respiratory depression was less pronounced than after heroin injection. No relevant bradycardia was noted. CONCLUSIONS: Opioid doses commonly prescribed in IV opioid treatment induce marked respiratory and circulatory depression, as well as occasionally irregular paroxysmal EEG activity. The extent of the observed effects raises questions about the appropriateness of IV opioid treatment in the present form.
  • Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment. (1999) DESIGN: Double-blind, cross-over design was used to compare the effects of a 33% increase in patient's daily dosage of methadone with a matched placebo. SUBJECTS: 18 patients on long-term methadone maintenance therapy. FINDINGS: Additional methadone significantly increased craving for heroin. Patients were unable to distinguish between additional methadone vs. additional placebo treatments. Patients were more alert and more contented following additional placebo than following additional methadone treatments. CONCLUSIONS: Additional methadone may "prime" cravings for heroin in methadone substitution patients.
  • Dose-response effects of methadone in the treatment of opioid dependence. (1993) DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: 247 opioid-dependent patients with a high rate of cocaine use. FINDINGS: By treatment week 20, retention was 52.4% for the 50-mg/day, 41.5% for the 20-mg/day, and 21.0% for the 0-mg/day group. Only the 50-mg/day treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg/day and 0-mg/day groups, respectively) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20-mg/day and 0-mg/day groups groups, respectively). CONCLUSIONS: In methadone maintenance therapy, only doses 50 mg/day or higher reduce opioid and cocaine use (by 22%).
  • Double-blind comparison of methadone and placebo maintenance treatments of narcotic addicts in Hong Kong. (1979) DESIGN: Randomized, double-blind, placebo-controlled trial. SUBJECTS: 100 heroin addict volunteers were initially admitted to hospital for two weeks for stabilisation on 60 mg of methadone before being assigned at random to two groups: one group received methadone (range 30-130 mg, average 97 mg/day); those in the other group had their dose of methadone reduced at the rate of 1 mg/day and were then maintained on placebo. FINDINGS: After thirty-two weeks 10% of the controls were still on treatment, compared with 76% of those receiving methadone. At the end of the three-year project, only 1 of the original 50 placebo subjects still turned up for treatment (2%), whereas the retention-rate (proportion still on treatment) for methadone subjects was 56%. CONCLUSIONS: At 3-years, methadone maintenance treatment retains only 56% of heroin addicts in treatment, but that is far superior to placebo treatment.

Does Methadone Maintenance Reduce Crime? (Studies Using Self-Reported Crime Are Excluded)

  • RESEARCH SUMMARY:
      FINDINGS:
      While in methadone maintenance treatment, 60%-70% of patients are still criminally active, and most are abusing multiple illicit drugs and alcohol. Self-reported crime by heroin addicts is notoriously unreliable.

      CONCLUSION:
      The only scientific way to prove if methadone maintenance therapy reduces crime is to conduct randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. In the 11 studies where this was done, it was shown that on average, methadone maintenance treatment does not decrease criminal behavior or mortality. However, for the few patients that stay in methadone maintenance treatment for 1-2 years, it has been shown to decrease criminal activity by about 20%-50%. Thus, for these long-attending methadone maintenance patients, treatment reduces shoplifting from 4 times/day to 3 or 2 times/day.

  • Engagement with opioid maintenance treatment and reductions in crime: a longitudinal national cohort study. (2012) DESIGN: Retrospective database analysis. SUBJECTS: Treatment data on all patients (3221) who started opioid maintenance therapy in Norway between 1997 and 2003 were cross-linked with national criminal records. FINDINGS: During opioid maintenance therapy, rates of criminal convictions for the cohort were reduced to fewer than half of waiting-list levels. Staying in opioid maintenance therapy for 2 years or more was associated with significantly reduced rates of convictions during treatment. Those who left treatment, permanently or temporarily, relapsed into high levels of convictions outside treatment. CONCLUSIONS: Criminal activity appears to be reduced in Norway during opiate maintenance treatment. Younger age and prior history of criminal activity are important risk factors for continued criminal activity during treatment. [Editor: Afghanistan supplies 80% of the world's opium (heroin) supply. In 1999-2001, Australia reported the mortality rate in opioid-addicts decreased 10-fold due to a world-wide decline in heroin availability caused by the Taliban stopping all opium (heroin) production in Afghanistan. Thus this study can't conclude that the observed decline in opioid-addict's criminal activity in their study was solely due to opiate maintenance treatment.]
  • Criminal convictions among dependent heroin users during a 3-year period prior to opioid maintenance treatment: a longitudinal national cohort study. (2011) DESIGN: Retrospective database analysis. SUBJECTS: All heroin users (N = 3,789) in Norway who applied for and were eligible for opioid maintenance treatment (1997-2003) were included. The opioid maintenance treatment records were cross-linked to Norwegian crime statistics. FINDINGS: During observation, 24,478 convictions were recorded among 60.9% of the sample. A large proportion (39.1%) had no convictions, whereas 10% of the sample was responsible for 37.8% of all convictions. Convictions for acquisitive crimes and drug crimes were the most common. CONCLUSIONS: The heavy involvement of heroin users with the criminal justice system provides an opportunity to intervene with dependent offenders. Coordination between treatment providers and police or courts can play an important role in improving outcomes through better access to treatment.
  • The effect of time spent in treatment and dropout status on rates of convictions, cautions and imprisonment over 5 years in a primary care-led methadone maintenance service. (2010) DESIGN: Cohort analysis. SUBJECTS: 108 consecutive heroin users entering a general practitioner-led methadone maintenance therapy (MMT). Ninety were followed-up for the full 5 years. MMT records were cross-linked to criminal conviction and caution rates and time spent in prison, derived from Police National Computer (PNC) criminal records. FINDINGS: The overall reduction in the number of convictions and cautions expected for patients entering MMT in similar primary care settings is 10% for each 6 months retained in treatment. Patients in continuous treatment had the greatest reduction in judicial disposal rates, similar to those who were discharged for positive reasons (e.g. drug free). Patients who had more than one treatment episode over the observation period did no better than those who dropped out of treatment. CONCLUSIONS: Methadone maintenance therapy delivered in a primary care clinic setting is effective in reducing convictions and cautions and incarceration over an extended period. Continuous treatment is associated with the greatest reductions.
  • Naltrexone implants compared to methadone: outcomes six months after prison release. (2010) DESIGN: Randomized clinical trail. SUBJECTS: 46 heroin-dependent inmates who volunteered to be randomly allocated to either naltrexone implants or methadone before release from prison. FINDINGS: Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release.
  • Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. (2009) DESIGN: Cochrane literature review of all randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. SUBJECTS: Eleven studies with 1969 patients. FINDINGS: Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment and in the suppression of heroin use as measured by self report and urine/hair analysis (RR = 0.66), but not statistically different in criminal activity or mortality. CONCLUSIONS: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not utilise opioid replacement therapy. Compared to no opioid replacement therapy for opioid dependence, methadone maintenance therapy does not show a statistically significant superior effect on criminal activity or mortality.
  • Medicaid coverage, methadone maintenance, and felony arrests: outcomes of opiate treatment in two states. (2009) DESIGN: Cohort analysis. SUBJECTS: More than 20,000 patients in methadone maintenance treatment (MMT) in USA. CONCLUSIONS: Only clients participating in MMT for many months showed much lower arrest rates than time not in treatment.
  • The impact of substitution treatment in prisons--a literature review. (2007) DESIGN: Literature review. FINDINGS: Prison-based methadone maintenance treatment (PMMT) can reduce drug use and injection in penal institutions. Moreover, PMMT provision can reduce injecting risk behaviours as well as drugs charges and re-admission rates. However, for PMMT to retain patients in treatment and reduce illegal drug use and criminal behaviour a sufficiently high dose of methadone (e.g., >60 mg) and the treatment duration lasting the entire period of imprisonment appear crucial. CONCLUSIONS: The authors recommend the provision of PMMT for individuals with long-standing opioid dependence.
  • Patterns of acquisitive crime during methadone maintenance treatment among patients eligible for heroin assisted treatment. (2007) DESIGN: Retrospectively assessed the self-reported illegal activities during 1 month of standard methadone maintenance treatment. SUBJECTS: 51 Dutch patients in methadone maintenance treatment. FINDINGS: In one month, 70% reported criminal activities and 50% reported acquisitive crimes. Offending took place on 20.5 days per month with on average 3.1 offences a day. Acquisitive crime consisted mainly of shoplifting (mean 12.8 days, 2.2 times/day) and theft of bicycles (mean 5.8 days, 2.4 times/day); theft from a vehicle and burglaries were committed less frequently. The majority of these patients (63%) reported to have started offending in order to acquire illicit drugs and alcohol. CONCLUSIONS: During methadone maintenance treatment, shoplifting, thefts and/or other property crimes were committed on average two to three times a day.
  • Patients receiving a prescription for diamorphine (heroin) in the United Kingdom. (2006) DESIGN: A retrospective case-note review was conducted in England and Wales. SUBJECTS: 210 patients' case-notes were reviewed. (Criminal activity was judged from self-reports). FINDINGS: Patients had been receiving a prescription for diamorphine for a median length of six years. The majority were unemployed white males, with a median age of 44 years. Illicit drug use and criminal activity, while low, had not been eliminated totally. CONCLUSIONS: The majority of patients had no serious drug, health or social problems.
  • Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s. (1999) DESIGN: A pre-post methadone treatment study spanning a 6-year time period (1987-1993). SUBJECTS: 126 methadone maintenance treatment patients. FINDINGS: Retention in methadone maintenance treatment has only a slight, though significant, effect on reducing criminal activity during treatment. Two other factors that appear to increase arrest activity are the use of cocaine and prior criminal history. CONCLUSIONS: The fact that arrests did not decrease during a treatment period of 18 months on average requires more investigation in light of the increase in cocaine use in this population.

Does Methadone Maintenance Reduce Mortality?

  • RESEARCH SUMMARY:
      FINDINGS:
      Heroin, methadone, and other opioid drugs are very addictive, and potentially very lethal drugs. It is easy to have an accidental fatal overdose on these opioids when they are mixed with alcohol or benzodiazepines. Likewise, it is easy to have an accidental fatal heart attack on these opioids when they are mixed with cocaine or methamphetamine. In America, the majority of drug intoxication deaths are due to opioids, and recently there has been a significant increase in opioid deaths. Heroin users, especially females, have a very high mortality rate; largely due to their high overdose rate. In Spain, the average heroin-addicted patient on methadone maintenance therapy died at age 39. Thus these heroin-addicted patients lost, on average, 38 years of life. Many heroin-addicted individuals abuse alcohol, cocaine and methamphetamine. Thus methadone maintenance therapy for their heroin addiction is, at best, only a partial treatment for their many addictions.

      CONCLUSION:
      The only scientific way to prove if methadone maintenance therapy reduces mortality is to conduct randomised controlled clinical trials of methadone maintenance therapy compared with either placebo maintenance or other non-pharmacological therapy for the treatment of opioid dependence. In the 11 studies where this was done, it was shown that on average, methadone maintenance treatment does not decrease mortality or criminal behavior. However, research has shown that, for severely heroin-addicted patients, mandatory treatment in a coercive residential setting with methadone maintenance is life-saving..

  • Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50,000 adults in Iran. (2012) DESIGN: Prospective cohort study in north eastern Iran, where opium consumption is exceptionally common. SUBJECTS: 50,045 participants aged 40-75 at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011. FINDINGS: Opium can be smoked, ingested or injected intravenously (in the form of heroin). Increased mortality was seen for each subtype of opium, with the strongest risk with heroin. Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases and cancer. Opium can have deleterious effects in the long term through causing hypotension, bradycardia, and respiratory depression that can increase myocardial infarct and mortality. Morphine, can result in hepatotoxicity. CONCLUSIONS: About 20 million people in the world use opium or its derivatives, and these individuals are at a substantially increased risk of death.
  • Drug-related death following release from prison: a brief review of the literature with recommendations for practice. (2011) DESIGN: Literature review. SUBJECTS: Prisoners newly released from prison. FINDINGS: Most deaths following release from prison are caused by overdose, usually from opioid use. The risk of death is greatest within the first week of release but, when compared with the general population, continues to be elevated for several weeks. Relative risk estimates suggest that those released from prison are up to 40 times more likely to die than similar individuals from the general population. In-prison pharmacological maintenance treatment with methadone and buprenorphine has been shown to reduce the rate of heroin use, in the period immediately following release, in a small number of randomised controlled trials. CONCLUSIONS: Continuity of care, of any form, is critical in avoiding drug related deaths following release from prison.
  • Treatment of opioid overdose in a physician-based prehospital EMS: frequency and long-term prognosis. (2011) DESIGN: Prospective study of all opioid overdose cases in one physician-based medical emergency care unit (MECU) over a 10-year period between 1994 and 2003 in Copenhagen. SUBJECTS: 4762 cases of acute opioid overdose. FINDINGS: The physician-based prehospital emergency medical service released 2246 patients (69.3%) after treatment, while 675 (20.8%) were admitted to hospital and 322 (9.9%) died. Long-term prognosis was poor with 14% mortality at 1 year. CONCLUSIONS: Long-term mortality is high in these patients and highest in those with advanced age and numerous episodes of opioid overdose.
  • The increasing mortality burden of liver disease among opioid-dependent people: cohort study. (2011) DESIGN: Data linkage study of methadone treatment entrants with the National Deaths Index. SUBJECTS: A cohort of 2489 people entering methadone treatment for heroin dependence in New South Wales, Australia, 1980-85. FINDINGS: There were 8.2 deaths per 1000 Per Year, with standardized mortality ratios (SMRs) of 4.6 (i.e., 4.6 times the standard mortality rate). Almost one in five (17%) of deaths were from underlying liver-related causes, most commonly viral hepatitis. The overall mortality rate for any liver cause was 1.4 deaths per 1000 Per Year, 17 times higher than that of the general population, with relative elevations more marked for females (SMR 27.9) than males (SMR 14.5). Liver mortality increased over time, becoming the most common cause of death by the end of follow-up. CONCLUSIONS: Liver disease has become the most common cause of mortality among ageing opioid-dependent people.
  • Prehospital treatment of opioid overdose in Copenhagen--is it safe to discharge on-scene? (2011) DESIGN: Prospective study of all opioid overdose cases in one physician-based medical emergency care unit (MECU) over a 10-year period between 1994 and 2003 in Copenhagen. SUBJECTS: 4762 cases of acute opioid overdose. Patients are released on scene if no residual signs of opioid intoxication are found after naltrexone treatment. FINDINGS: Of the 2241 opiod patients whose opioid overdose was treated with naloxone, then released without being sent to hospital, only 14 (0.13%) died within 48 hours. CONCLUSIONS: Prehospital discharge-on-scene after naloxone treatment for an opioid overdose is associated with a low risk of death due to rebound toxicity.
  • Increasing cancer mortality among opioid-dependent persons in Australia: a new public health challenge for a disadvantaged population. (2011) DESIGN: New South Wales opioid substitution therapy (OST) program registrants from 1985 to 2005 were probabilistically linked to the National Death Index. SUBJECTS: 43,789 patients. FINDINGS: Overall, OST registrants were 1.7 times more likely to die of cancer than the general population. These patients were 3.6 times more likely to die of lung cancer, 6.9 times more likely to die of liver cancer, 2.8 times more likely to die of anogenital cancers, but had a significantly reduced risk of dying from breast cancer. CONCLUSIONS: Cancer is an increasingly important cause of death among opioid substitution therapy registrants. This cancer appears due to tobacco, alcohol, and infection with hepatitis C and human papillomavirus.
  • Estimating the risk of fatal arrhythmia in patients in methadone maintenance treatment for heroin addiction. (2011) DESIGN: Retrospective cohort study. SUBJECTS: The study covered 14,500 patient-years (pys) in methadone treatment. FINDINGS: Fatal arrhythmia occurred at a rate of 0.014 per 100 patient-years. Overdose is a more common cause of death. Both potential arrhythmias and overdoses were associated with use of other drugs in addition to methadone usually, prescription drugs or methamphetamine. CONCLUSIONS: The risk of fatal cardiac arrhythmia in methadone maintenance patients appears to be low. The major risk factor for death was use of prescription drugs, and methamphetamine, in addition to methadone.
  • Deaths of opiate/opioid misusers involving dihydrocodeine, UK, 1997-2007. (2011) DESIGN: Retrospective database analysis of opioid overdose deaths involving dihydrocodeine between 1997 and 2007. SUBJECTS: 584 fatalities. FINDINGS: Although its effectiveness is somewhat controversial, it appears that dihydrocodeine (DHC) is still prescribed in the UK as an alternative to both methadone and buprenorphine for the treatment of opiate addiction. Dihydrocodeine, either alone or in combination, was identified in 6.8% of all opiate/opioid-related deaths during this period. Typical DHC cases identified were white males in their early thirties. In the majority (55%) of overdoses, DHC had not be prescribed to the patient (i.e., DHC was obtained illegally). CONCLUSIONS: Co-administration of DHC with heroin, methadone and benzodiazepines increases the risk of accidental fatal overdose. Prescribers should use alternatives to dihydrocodeine (e.g. methadone, buprenorphine) when managing and treating opiate addiction.
  • Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997-2007. (2011) DESIGN: Retrospective analysis of data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner. SUBJECTS: 2900 drug intoxication deaths. FINDINGS: Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. CONCLUSIONS: By far, the majority (77%) of drug intoxication deaths in Connecticut are due to opioids, and there has been a significant increase in opioid deaths.
  • Rates and correlates of mortality amongst heroin users: findings from the Australian Treatment Outcome Study (ATOS), 2001-2009. (2011) DESIGN: Prospective cohort study over the period 2001-2009. SUBJECTS: 615 heroin users. FINDINGS: 5% of the heroin users died over this 9 year period. The mean age at death was 34.5 years, and 58% were male. The most common cause of death was overdose (68%). The male mortality rate was 2.95 times higher than the general population. However, the female mortality rate was 18.57 times higher than the general population. Their combined mortality rate was 4.56 times higher than the general population. The mean age at death was 34.5 years, and 58% were male. The most common cause of death was overdose (68%). The only predictor of overdose death was a history of prior overdose. CONCLUSIONS: Heroin users, especially females, have a very high mortality rate; largely due to their high overdose rate. These Australian mortality rates are lower than those reported in North America or Europe.
  • Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies. (2011) DESIGN: Literature review. SUBJECTS: Fifty-eight prospective studies reported mortality rates from opioid-dependent samples. FINDINGS: Opioid addicts have a mortality rate 14.66 times higher than the general population. Females have a higher mortality rate than males. Out-of-treatment periods had a 2.38 times higher mortality risk than in-treatment periods. Overdose was the most common cause of death. Injecting opioids has a higher mortality than smoking or ingesting opioids. CONCLUSIONS: Treatment is clearly protective against mortality among opioid-dependent users.
  • Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database. (2010) DESIGN: Prospective cohort study. SUBJECTS: 5577 primary care opioid-dependent patients prescribed methadone or buprenorphine during 1990-2005. FINDINGS: Opioid-dependent patients had a mortality rate 5.3 times higher than the general population on treatment, and 10.9 times higher than the general population off treatment. Men using opiates had approximately twice the risk of death of women. CONCLUSIONS: Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months. However, there is increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment.
  • Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland. (2010) DESIGN: Analysis of annual trends in deaths related to overdose of methadone in Scotland and England between 1993 and 2008. FINDINGS: There was a four-fold decrease in number of deaths with methadone (implicated per million defined daily doses of methadone prescribed in that year) between 1993 and 2008. CONCLUSIONS: Introduction of supervised methadone dosing was followed by substantial declines in deaths related to overdose of methadone in both Scotland and England.
  • Mortality and employment after in-patient opiate detoxification. (2012) DESIGN: Prospective cohort study linking medical records to survival and employment records from the Austrian Social Security Institution. SUBJECTS: 404 pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Followup was up to 11 years. FINDINGS: 58.7% completed the detoxification program. Mortality rates were between 13.5 and 17.9 times higher than the general population during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts. CONCLUSIONS: The assumption that completers of voluntary in-patient detoxification treatment have a better outcome than non-completers has not been confirmed. Opioid or poly-substance addicts have very high mortality and unemployment rates.
  • Were the changes to Sweden's maintenance treatment policy 2000-06 related to changes in opiate-related mortality and morbidity? (2010) DESIGN: Surveys of all Swedish methadone maintenance treatment units, of buprenorphine and methadone sales, and of mortality and inpatient care in Sweden. FINDINGS: Sales of buprenorphine and methadone and the number of patients in treatment increased more than threefold from 2000 to 2006, with the greatest increase for buprenoprphine, introduced in year 2000. There was a significant 20-30% reduction in opiate-related mortality and inpatient care between 2000-2002 and 2004-2006 but not of other drug-related mortality and inpatient care. However, a significant increase in buprenorphine- and methadone-related mortality occurred. CONCLUSIONS: The liberalization of Sweden's drug policy correlated with an increase in maintenance treatment, a decrease in opiate-related mortality and inpatient care and an increase in deaths with methadone and buprenorphine.
  • Impact of slow-release oral morphine on drug abusing habits in Austria (2010) DESIGN: Retrospective database analysis of opiate maintenance treatment programmes in Austria. FINDINGS: Since 1998 the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market. The intravenous consumption of SROM has highly dangerous side effects that exceed the risks of needle sharing alone. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Slow-release oral morphine has been the main cause of most drug related deaths since its introduction in 1998. CONCLUSIONS: The widespread use of slow-release oral morphine in opiate maintenance treatment programmes should be avoided.
  • Favorable mortality profile of naltrexone implants for opiate addiction. (2010) DESIGN: Prospective follow-up of patients treated with naltrexone implant and buprenorphine. SUBJECTS: 255 naltrexone implant patients were followed for 5.2 years, and 2,518 buprenorphine patients were followed for 3.2 years. FINDINGS: The mortality rate for naltrexone implants was 67.6% that of the mortality rate of buprenorphine.
  • 15-Year survival and retention of patients in a general hospital-affiliated methadone maintenance treatment (MMT) center in Israel. (2010) DESIGN: Prospective 15-year follow-up of methadone maintenance treatment patients. SUBJECTS: 613 patients. FINDINGS: 15.3% of the patients died. Cancer was the primary cause of death for those who remained in treatment, and overdose for those who left MMT. Benzodiazepine abuse reduced both retention and survival, emphasizing the high priority that should be given to stopping it. CONCLUSIONS: Staying in methadone maintenance treatment for more than 1 year did not significantly lower the mortality rate.
  • A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. (2009) DESIGN: All people dying from unintentional overdoses of methadone or other opioid analgesics (OOA) in West Virginia in 2006. SUBJECTS: 250 overdose deaths. FINDINGS: The methadone group included 87 decedents (34.8), and the OOA group included 163 decedents (65.2%). Most were male. Decedents in the methadone group were significantly younger than those in the OOA group: more than a quarter were 18-24 years of age. For both groups, approximately 50% had a history of pain, and 80% had a history of substance abuse. There was no intergroup difference in the prevalence of benzodiazepines at post-mortem. Methadone was significantly less likely to have ever been prescribed than OOA. Ten (11.5%) of the methadone decedents were enrolled in an opiate treatment program (OTP) at the time of death. CONCLUSIONS: The high prevalence of a substance abuse history and lack of prescriptions suggest that most of the deaths in both groups are related to substance abuse. Physicians should use state prescription drug monitoring programs to monitor the use of controlled substances by their patients.
  • Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: risk factors and lives saved. (2009) DESIGN: Retrospective database analysis linking the New South Wales (NSW) Pharmaceutical Drugs of Addiction System with data from the National Deaths Index, a record of all deaths in Australia for 1985-2006. SUBJECTS: 42,676 people entering opioid replacement therapy. FINDINGS: Mortality among 42,676 people entering opioid pharmacotherapy was elevated compared to age and sex peers. Drug overdose and trauma were the major contributors. Mortality was higher out of treatment, particularly during the first weeks, and it was elevated during induction onto methadone but not buprenorphine. Overall, mortality was similarly reduced (compared to out-of-treatment) whether patients were receiving methadone or buprenorphine. CONCLUSIONS: It was estimated that the program produced a 29% reduction in mortality across the entire cohort.
  • Overdose deaths following previous non-fatal heroin overdose: record linkage of ambulance attendance and death registry data. (2009) DESIGN: Retrospective cohort design linking ambulance attendance records in Melbourne, Australia over a 5-year period (2000-2005) with a national death register. SUBJECTS: 4884 people. FINDINGS: 3.4% of those patients with a previous non-fatal heroin overdose go on to have a subsequent fatal overdose. Mortality rate decreased 10-fold after 2000 coinciding with widely reported declines in heroin availability. [Editor: Afghanistan provides 80% of the world's opium. In 2000, the Taliban stopped all opium growing in Afghanistan.] Being male, of older age (>35 years) and having been attended multiple times for previous non-fatal overdoses were associated with increased mortality risk. CONCLUSIONS: This study shows the profound effect of macro-level heroin market dynamics on overdose mortality.
  • Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. (2009) DESIGN: Data linkage study comparing retention in treatment and mortality among people entering methadone and buprenorphine treatment for opioid dependence. SUBJECTS: 5992 patients. FINDINGS: Median retention was significantly longer in methadone (271 days) than buprenorphine (40 days). During induction, the risk of death was lower for buprenorphine. Risk of death was lowest during treatment, significantly higher in the first 12 months after leaving both methadone and buprenorphine. Beyond 12 months after leaving treatment, risk of death was non-significantly higher than during treatment. CONCLUSIONS: Buprenorphine was safer during induction. Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death.
  • Factors associated with mortality in Scottish patients receiving methadone in primary care: retrospective cohort study. (2009) DESIGN: Retrospective cohort study of patients prescribed methadone in Scotland between January 1993 and February 2004. SUBJECTS: 2378 patients. FINDINGS: 181 (8%) people died. Overuse of methadone, history of psychiatric admission, history of prescription of benzodiazepines, and increasing comorbidity were all associated with an increase in mortality. Drug dependence was identified as the principal cause of death in 60 (33%) people. CONCLUSIONS: [Editor: This extremely high mortality rate of 8% per year for methadone maintenance patients suggests that this program is ineffective.]
  • Comparing overdose mortality associated with methadone and buprenorphine treatment. (2009) DESIGN: Data linkage study for 9-month period comparing overdose mortality associated with methadone and buprenorphine treatment for opioid dependence. SUBJECTS: 13,718 patients in methadone treatment and 2716 patients in buprenorphine treatment. FINDINGS: There were 60 (0.4%) sudden deaths positive for methadone (32 in-treatment) and 7 (0.3%) buprenorphine-positive decedents (none in treatment). Most out-of-treatment deaths occurred in people with known histories of drug misuse. Forty-three methadone positive cases - 19/32 in treatment, and 24/28 out-of-treatment - and 2 of the 7 buprenorphine-positive deaths were due to overdose. The risk of overdose death per thousand people in treatment was lower for buprenorphine than for methadone (RR 4.25). CONCLUSIONS: In this short-term study, buprenorphine was associated with lower overdose risk than methadone.
  • Mortality among opiate users: opioid maintenance therapy, age and causes of death. (2009) DESIGN: Data on all opiate dependents in Norway (1997-2003) enrolled in opioid maintenance therapy (OMT). SUBJECTS: 3789 patients. FINDINGS: Overall death rate was 1.9%. Deaths were due to drug overdose (54%), somatic (32%) and traumatic causes (14%). Overdose deaths among all age groups were reduced during opioid maintenance therapy. Deaths during OMT were most likely to be due to somatic causes. CONCLUSIONS: The high prevalence among older patients of deaths due to somatic causes has implications for screening, treatment and referral.
  • Psychiatric comorbidity reduces quality of life in chronic methadone maintained patients. (2009) DESIGN: Diagnostic evaluation of chronic methadone maintained patient. SUBJECTS: 193 middle-aged patients in long-term methadone maintenance treatment (MMT). FINDINGS: Psychiatric comorbidity was documented in 78% of the patients. Mood disorders (60%) and anxiety disorders (46%) were the most common diagnoses. Additional substance use disorders were diagnosed in 70% of the MMT patients. A probable personality disorder was documented for (125) 65% of the patients. Antisocial personality disorder was diagnosed in 66 (34.2%) of these patients. Quality of Life was severely diminished to a level comparable to that for patients with chronic psychiatric and/or somatic disorders. CONCLUSIONS: The quality of life for MMT patients is generally low. The present results showed a high rate of psychiatric comorbidity for this patient group.
  • Methadone- and heroin-related deaths in Florida. (2008) DESIGN: Florida Department of Law Enforcement data were analyzed to examine trends in deaths related to or caused by methadone and/or heroin between 2001-2006. FINDINGS: Mortalities associated with methadone use increased steadily as mortalities associated with heroin decreased steadily. CONCLUSIONS: Methadone possesses high abuse potential and documented mortality risks.
  • Mortality in opioid-maintained patients after release from an addiction clinic. (2008) DESIGN: Retrospective cohort study. SUBJECTS: 269 opioid-dependent patients enrolled in synthetic opioid maintenance therapy from 1998 to 1999 originally at the Addiction Clinic and then discharged to general practitioners. FINDINGS: From 29 fatalities, 37.9% died of intoxication with illicit substances, 34.5% related to AIDS and 27.6% of somatic complications. The mortality rate was 29 times higher than that of the standard population (i.e., SMR 29.13). A higher lifetime frequency of hospitalization, less working days and a lack of social relationships were factors associated with high mortality. CONCLUSIONS: Although great efforts were undertaken in locating patients, about 45% of the target group could not be located.
  • Mortality of drug users attending public treatment centers in Italy 1998-2001: a cohort study (2007) DESIGN: Cohort follow-up study of heroin users attending Public Treatment Centers (PTCs) in Italy enrolled between 1998-2000 and followed-up in 2001. The observation time is mainly for the time these patient were in treatment. SUBJECTS: 10,376 patients (8881 men and 1495 women). FINDINGS: 190 (1.8%) deaths occurred during the study period (153 men and 37 women): 70 deaths were due to overdose (36.8%), 38 to AIDS (20.0%), 30 to violence (15.8%). For women, the mortality rate was 22.8 times higher than that of the standard population (i.e., SMR 22.8). For men, the mortality rate was 6.7 times higher than that of the standard population (i.e., SMR 6.7). CONCLUSIONS: In Italy, approximately 13% of deaths in people in their 30s can be attributed to heroin addiction (i.e., 14.4% of deaths in people aged 30-34, 12.8% at age 35-39, and 10.7% at age 25-29).
  • A 20-year prospective study of mortality and causes of death among hospitalized opioid addicts in Oslo. (2008) DESIGN: Prospective 20-year folow-up cohort study among all hospitalized opioid addicts treated for self-poisoning or admitted for voluntary detoxification in Oslo between 1980 and 1981. SUBJECTS: 185 opioid addicts. Their median age was 24 years; with a range from 16 to 41, and 53% were males. FINDINGS: During a period of 20 years, 70 (37.8%) opioid addicts died. Their mortality rate was 23.6 times higher than that of the standard population (i.e., SMR 23.6). The Standard Mortality Ratio (SMR) remained high during the whole period, ranging from 32.4 in the first five-year period, to 13.4 in the last five-year period. There were no significant differences in SMR between self-poisonings and those admitted for voluntarily detoxification. The SMR was 5.4 for cardiovascular diseases, and 4.3 for cancer. The SMR was 13.2 for accidents, 10.7 for suicides, and 28.6 for other violent deaths. CONCLUSIONS: The risk of death among opioid addicts was significantly higher for all causes of death compared with the general population, implying a poor prognosis over a 20-year period for this young patient group.
  • Mortality prior to, during and after opioid maintenance treatment (OMT): a national prospective cross-registry study. (2008) DESIGN: Pospective cross-registry study with up to 7 years follow-up. SUBJECTS: All opiate dependents in Norway who applied for OMT (a total of 3789 subjects) were cross-linked with data from the death registry from Statistics Norway. A baseline was established from the waiting list mortality rate. Intention-to-treat was investigated by analysing mortality among the entire population that started OMT. FINDINGS: In the "intention-to-treat" perspective, the mortality risk was reduced to RR 0.6 compared with pre-treatment. The patients who left the treatment programme showed a high-mortality rate, particularly males. CONCLUSIONS: OMT significantly reduces risk of mortality also when examined in an intention-to-treat perspective. Studies that evaluate effects of OMT only in patients retained in treatment tend to overestimate benefits.
  • Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi-site prospective cohort study. (2007) DESIGN: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for almost 1 year in treatment and 3 months out of treatment. SUBJECTS: 10,454 heroin users entering treatment 1998-2001 in Italy. FINDINGS: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 and 21.4, respectively. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period. CONCLUSIONS: The considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes.
  • Cocaine- and opiate-related fatal overdose in New York City, 1990-2000. (2007) DESIGN: Retrospective registry analysis: data were collected from the NYC Office of the Chief Medical Examiner on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000. Overdoses were classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). SUBJECTS: 8,774 fatal overdoses. FINDINGS: 40.5% of the fatal overdoses were attributed to cocaine and opiates, 32.2% were attributed to opiates-only, and 27.3% were attributed to cocaine only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%.
  • Observed patterns of illicit opiate overdose deaths in Chicago, 1999-2003. (2007) DESIGN: Retrospective registry analysis. Examined data from every death certificate filed between 1999 and 2003 to identify all Chicago residents' accidental deaths involving acute intoxication with illicit opiates, OD, or opiate poisoning. FINDINGS: OD incidence peaked in 2000 and then declined markedly by 2003. Over the 2000-2003 period, overall incidence of fatal OD declined by 34%. Over this period, the sharpest observed declines occurred among African-Americans and Hispanics/Latinos. The opiate-related fatality incidence also declined among non-Hispanic whites. CONCLUSIONS: In 2003, illicit opiate-related OD accounted for 35% of all accidental deaths to Chicago adults aged 18-64, with 45% of OD deaths occurring among African-American men.
  • Years of potential life lost among heroin addicts 33 years after treatment. (2007) DESIGN: Longitudinal, prospective study following male heroin addicts in California for more than 33 years. SUBJECTS: 581 male heroin addicts. FINDINGS: 33 years after treatment, 48.5% were confirmed as deceased by death certificates. On average, addicts in this cohort lost 18.3 years of potential life before age 65 (22.3% of the years lost was due to heroin overdose, 14.0% due to chronic liver disease, and 10.2% to accidents). CONCLUSIONS: The total years of potential life lost among addicts was much higher than that in the national population; within the cohort, premature mortality was higher among Whites and Hispanics compared to African American addicts.
  • One-year mortality rates of patients receiving methadone and buprenorphine maintenance therapy: a nationally representative cohort study in 2694 patients. (2006) DESIGN: Prospective cohort study: opioid dependent patients in substitution treatment either with methadone or buprenorphine at baseline were monitored over a 12-month period. SUBJECTS: 2694 opioid dependent patients. FINDINGS: 60.4% were still in treatment after 12 months. The overall mortality rate was 1.04%. In total, 28 patients of the initial sample deceased within the 1-year follow-up period. Eleven (0.4%) of these deaths are due to a fatal intoxication. Three patients (0.1%) died of human immunodeficiency virus/acquired immunodeficiency syndrome, and 3 (0.1%) committed suicide. Thirteen of these patients (4 with overdose/polyintoxication) were not in substitution treatment at the time of death. The mortality rate was similar in methadone as compared with buprenorphine patients. CONCLUSIONS: The mortality rate of approximately 1% confirms that maintenance treatment could be regarded as a fairly safe treatment.
  • Trends in opioid-related fatal overdoses in Massachusetts, 1990-2003. (2006) DESIGN: Retrospective registry analysis. Massachusetts death files for the years 1990-2003 were used to identify all poisoning deaths and opioid-related poisoning deaths. FINDINGS: From 1990 to 2003, opioid-related fatal poisoning rates increased by 529% from 1.4 per 100,000 in 1990 to 8.8 per 100,000 in 2003. The proportion of total poisoning deaths associated with opioids rose from 28% in 1990 to 69% in 2003. CONCLUSIONS: Since 1997, poisoning, particularly from heroin and other opioids, has been the leading cause of injury mortality in Massachusetts.
  • Drug-related mortality and its impact on adult mortality in eight European countries. (2006) DESIGN: Retrospective cohort study: Opiate users in eight drug treatment centres in Europe during 1990-1998 were followed up through national or local mortality registries. FINDINGS: The mortality rate for male opioid users in Barcelona was 21.1 times that of the standard population (i.e., standardized mortality ratio [SMR] 21.1). The mortality rate for female opioid users in Barcelona was 53.7 times that of the standard population (i.e., SMR 53.7), and in Rome it was 37.7 times that of the standard population (i.e., SMR 37.7). The highest drug-related mortality rate was 10 per 1,000 person-years in Barcelona; the rates were approximately 7 per 1,000 person-years in Denmark, London, Rome, and Vienna, and <3.5 per 1,000 person-years for the others cohorts. The mortality rate for AIDS was <2 per 1,000 person-years in all the cohorts except Lisbon, Rome, and Barcelona, for which it was approximately 6 per 1,000 person-years. CONCLUSIONS: For opioid users, Barcelona and Rome have significantly higher drug-related and AIDS-related mortality rates compared to 6 other European cities. Overall, European opioid users have very high drug-related and AIDS-related mortality rates.
  • Mortality in heroin-assisted treatment in Switzerland 1994-2000. (2005) DESIGN: Retrospective registry analysis: 7-year (1994 to 2000) follow-up of all participants in heroin-assisted treatment in Switzerland. FINDINGS: Over the 7-year period, the crude death rate of patients in heroin-assisted treatment, and including one month after discharge from treatment, was 1% per year. The standardized mortality ratio for the entire observation period was 9.7, with females having higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was no clear time trend. CONCLUSIONS: Mortality in heroin-assisted treatment was low compared to the mortality rate of Swiss opioid users 1990s (estimated to be between 2.5 and 3%). It was also low compared to mortality rates of opioid users in other maintenance treatments in other countries as reported in the literature. The SMR was also lower than that reported in the only meta-analysis in the literature: 13.2. The low mortality rate is all the more noteworthy as heroin-assisted treatment in Switzerland included only refractory opioid addicts with existing severe somatic and/or mental problems.
  • Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain. (2005) DESIGN: Prospective cohort study of all heroin-addicted patients who started methadone maintenance treatment between 1992 and 1997. Follow-up assessments were carried out every 9 months until 2000. SUBJECTS: 5049 patients followed for an average of 4.6 years. FINDINGS: Fifty per cent were in methadone maintenance treatment (MT) during the study period; of the total cohort 1005 (19.9%) patients died. Of the deaths: 38.4% were due to AIDS, 34.7% to overdose and 27% to other causes. Overall mortality decreased from 5.9 deaths per 100 person-years in 1992 to 1.6 in 1999. Globally, life expectancy at birth was 39 years, 38 years lower than that of the general population. The main factor for overdose mortality was not being in MT at the time of death [relative ratio (RR) = 7.1]; other factors were being a current injector at baseline and being HIV positive. For AIDS mortality, the main factor was the calendar year (RR for 1996 versus 1999 = 4.6), the next major factor was more than 10 years of heroin consumption, followed by not being in MT, being unemployed, then having a prison record. CONCLUSIONS: The observed mortality decline could be linked to the effectiveness of low-threshold methadone maintenance treatment. The life expectancy of heroin users increased by 21 years during the study period. [Editor: Afghanistan supplies 80% of the world's opium (heroin) supply. In 1999-2000, Australia reported the mortality rate in opiod-addicts decreased 10-fold due to a world-wide decline in heroin availability caused by the Taliban stopping all opium (heroin) production in Afghanistan. Thus this study can't conclude that the observed mortality decline at the end of their study period (2000) was solely due to "the effectiveness of low-threshold methadone maintenance treatment".]
  • Drug-use pattern, comorbid psychosis and mortality in people with a history of opioid addiction. (2005) DESIGN: Prospective cohort study comparing the 15-year mortality of people with a history of intravenous narcotics addiction that had achieved stable abstinence, with the mortality associated with continued drug use. SUBJECTS: 188 persons (122 men and 66 women). FINDINGS: About 32% had died during the 15-year follow-up. The 15-year mortality associated with stable abstinence from injecting narcotics was reduced by 56% when compared with the perceived worst drug-use pattern. Hospitalization for comorbid psychosis was not independently associated with mortality in this sample. The standard mortality rates (SMRs) were clearly elevated. Even for those that achieved stable abstinence from injecting narcotics, their mortality rate was at least 7-times higher than that of the standard population. CONCLUSIONS: People who had achieved stable abstinence from injecting narcotics use were at lower risk of premature death than people with continued drug use. A residual observed excess mortality in people who had apparently achieved stable abstinence from drug use is consistent with the view of drug addiction as a chronic disease.
  • Changes in mortality, arrests, and hospitalizations in nonvoluntarily treated heroin addicts in relation to methadone treatment. (1998) DESIGN: Prospective cohort study analyzing the mortality, hospitalizations, and arrests in a cohort of severe intravenous heroin users divided into three groups: those in methadone treatment, those discharged from treatment, and those who never received treatment. SUBJECTS: 101 heroin users, of whom 56 were HIV-seropositive. Because of intensive drug misuse, they underwent coercive residential treatment in Stockholm during the 3-year period 1986-1988. FINDINGS: The mortality was lower in the methadone group, and all seven deaths were related to HIV-infection. Outside the program, 24 of 29 persons died from external violence and poisoning. CONCLUSIONS: Coercive residential treatment giving methadone maintenance for severe intravenous heroin users was dramatically more effective than no treatment.

Does Opioid Abstinence Reduce Mortality?

  • RESEARCH SUMMARY:
      FINDINGS:
      At 15-year followup, 32% of individuals with opioid use disorder have died. Abstinence from opioid use reduces this 15-year mortality rate by 56%. However, at 15-year followup, even those that become abstinent still have a 7-fold elevation in standardized mortality rate.

      CONCLUSION:
      Opioid use disorder is a chronic and very lethal disorder. However, the mortality rate can be halved by stopping opioid use. However, even off opioids, these individuals still have mortality rates 7-times higher than the standard population.

  • Drug-use pattern, comorbid psychosis and mortality in people with a history of opioid addiction. (2005) This Danish study compared the 15-year mortality of people with a history of opioid dependence that had achieved stable abstinence, with the mortality associated with continued drug use. About 32% had died during the 15-year follow-up. Abstinence from opioid use reduced the 15-year mortality by 56% when compared with the mortality rate of those without abstinence. Even in the stably abstinent group, the standardized mortality rate was significantly elevated by at least seven-fold in both genders.

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