Psychosis after buprenorphine, heroin, methadone, morphine, oxycodone, and tramadol withdrawal: a systematic review

Eur Rev Med Pharmacol Sci. 2021 Jul;25(13):4554-4562. doi: 10.26355/eurrev_202107_26248.


Objective: This study's main objective is to carry out a systematic review of the onset of psychotic symptoms after opioid withdrawal. The opiate dependence correlated to psychiatric symptoms has been well described.

Materials and methods: Following the PRISMA methodology. The consecutive search strategy was applied: (morphine OR buprenorphine OR oxycodone OR tramadol OR fentanyl OR remifentanil OR opioids OR heroin OR methadone) AND (Psychosis OR psychotic symptoms OR schizophrenia).

Results: 12 case reports, 3 series of cases, 2 clinical studies, and 2 reviews were found. It seems that the time association is present in all of them; symptoms appear days after the interruption of the opioid. Most of the articles reported are case reports that describe symptoms that appear after the suspension of the opioid substance; in most cases, the reintroduction of the opioid had therapeutic effects and provoked a remission of these symptoms. These preliminary findings indicate that opiates could have an antipsychotic effect; however, the literature is scarce. It is critical to consider, if needed, in opioid-dependent patients who start with psychosis after the opioid withdrawal the possible replacement or reintroduction of opioids to prevent further deterioration in the patient's mental status.

Conclusions: This study encompasses a comprehensive description of the literature concerning the possible not well-studied outcome of opioid withdrawal. There are some reports of temporal association between withdrawal and psychotic symptoms that improved after the reintroduction of the opioid; it could be taken into consideration in the clinical practice.

Publication types

  • Systematic Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Buprenorphine / adverse effects
  • Heroin / adverse effects
  • Humans
  • Methadone / adverse effects
  • Morphine / adverse effects
  • Oxycodone / adverse effects
  • Psychotic Disorders / epidemiology*
  • Psychotic Disorders / etiology
  • Psychotic Disorders / psychology
  • Substance Withdrawal Syndrome / psychology*
  • Tramadol / adverse effects


  • Analgesics, Opioid
  • Tramadol
  • Buprenorphine
  • Heroin
  • Morphine
  • Oxycodone
  • Methadone