Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study

BMJ 2003; 326 doi: (Published 03 May 2003) Cite this as: BMJ 2003;326:959
  1. John Strang (j.strang{at}, professor and director,
  2. Jim McCambridge, senior research worker,
  3. David Best, senior lecturer, addictions,
  4. Tracy Beswick, research worker,
  5. Jenny Bearn, consultant psychiatrist, addictions,
  6. Sian Rees, research worker,
  7. Michael Gossop, professor
  1. National Addiction Centre, Institute of Psychiatry and the Maudsley Hospital, London SE5 8AF
  1. Correspondence to: J Strang
  • Accepted 30 January 2003

In many countries opiate overdose remains the main source of the 10-fold excess mortality among opiate addicts, notwithstanding the effects of HIV/AIDS.1 Treatment reduces mortality but can sometimes increase mortality transiently—for example, during the first few weeks of methadone maintenance treatment and among former opiate addicts after their release from prison. 2 3 The increase in mortality among released prisoners who were formerly opiate addicts has been attributed to loss of tolerance and erroneous judgment of dose when they returned to opiate use. 1 3 We wished to investigate whether opiate addicts who have undergone inpatient detoxification might have a similarly increased mortality after treatment. We followed up patients who received inpatient opiate detoxification, looked for evidence of increased mortality, and investigated the distinctive characteristics of patients who died.

Predictors of mortality among patients who underwent inpatient opiate detoxification. Values are numbers (percentage) of patients unless stated otherwise

View this table:

Participants, methods, and results

Over 20 months we recruited 137 consecutive opiate addicts who were receiving opiate detoxification as part of a 28 day inpatient treatment programme and who consented to be followed up. Five patients died within 12 months after their discharge from the inpatient unit, of whom three had died after a drug overdose within the first four months after discharge. We successfully interviewed 103 patients (at a mean interval of 8.7 months after discharge). A search of records indicated that the remaining 29 patients were still alive one year after discharge.

To test whether loss of tolerance increased the risk of overdose, we grouped the patients into three categories, according to their opiate tolerance at the point of leaving treatment: 43 “still tolerant” (ST) patients who failed to complete detoxification; 57 “reduced tolerance” (RT) patients who completed the prescribed phase of detoxification but who prematurely left the treatment programme; and 37 “lost tolerance” (LT) patients who completed the detoxification and also completed the inpatient treatment programme.

The three overdose deaths that occurred within four months after treatment were all from the LT group; the two deaths unrelated to overdose (although both these patients had relapsed) were one LT patient with end stage renal failure and one RT patient with Clostridium welchii infection; no deaths occurred in the ST group (Fisher's exact test, df=2, P=0.02). This clustering did not derive from differences in duration to the follow up interview (mean durations were 9.5 months (ST), 8.7 months (RT), and 7.8 months (LT)).

We also considered length of time in treatment as a continuous variable. The five patients who died had stayed longer in the inpatient unit (mean 24.6 days (SD 7.6)) than the other 132 patients (15.6 days (8.1)) (t=2.44, P=0.02) (table). We looked for distinctive premorbid characteristics among the patients, all men, who died—possible clinical markers of risk of mortality after detoxification. Before admission these patients were more likely than the other patients to have been living alone, to have been taking higher doses of methadone, and to have been using heroin less often. They stayed longer in the inpatient unit and were more likely to have completed the treatment programme.


Patients who “successfully” completed inpatient detoxification were more likely than other patients to have died within a year. No patients who failed to complete detoxification died. Heroin addicts are known to have excess mortality.4 However, on the basis of previously published data we would have expected that in our group only one or two patients would have died within a year and only one from overdose.5 The clustering of the deaths from overdose in the group of patients who had successfully completed treatment is counterintuitive and illogical—unless it derives from loss of tolerance and consequent unpredictability of resumed heroin use. This study urgently requires replication, and if its results are confirmed these will need to be addressed within existing inpatient, residential, and custodial and associated aftercare programmes.


We thank the patients and staff of Wickham Park House, Bethlem Royal Hospital, South London and Maudsley NHS Trust.

Contributors: JS conceived the analysis of data from the follow up study designed by DB, JB, MG, and JS. TB and SR collected and entered the data. Statistical analysis was by JMcC and JS. JS and JMcC wrote the original draft, and all authors contributed to interpretation and revision. JS and DB are the guarantors.


  • Funding Henry Smith Charitable Foundation.

  • Competing interests None declared.

  • Ethical approval: South London and Maudsley ethical committee.


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