LETTER TO THE EDITORS
Possible Psychosis Associated With Buprenorphine Withdrawal To the Editors: uprenorphine is widely used in managing opioid dependence and is primarily a partial mu agonist and kappa antagonist at the opioid receptors.1 Buprenorphine also has possible effects on mood.2,3 In addition, buprenorphine has been reported to both cause psychosis4,5 and have possible antipsychotic6 properties. Only 2 earlier instances of acute psychosis caused after buprenorphine withdrawal7,8 have been reported, which, however, also had a history of psychosis and comorbid polysubstance use. We are reporting the third case of possible buprenorphine withdrawal–associated acute psychosis in a patient with no history and no other substance misuse.
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CASE REPORT A 40-year-old man brought for management of opioid withdrawal symptoms was treated with buprenorphine 16 mg administered during a 2-week inpatient setting, with regular ongoing monitoring of his withdrawal and mental state. He had no history of any other psychiatric illness or use of other substances, with the exception of opioids. On review in the second week after discharge, his wife reported a significant change in his behavior. Mental state assessment revealed clear referential and persecutory delusions along with accompanying visual hallucinations. There was no evidence of delirium and his sensorium was normal. There were no clinical signs or symptoms of opioid withdrawal. All routine investigations including neuroimaging (computed tomography of the brain) at this time showed normal results. Urine drug screen was negative for any other substance. He had no family history of any psychiatric illness including any psychotic spectrum disorders. On further probing, it was found that the client had abruptly stopped buprenorphine 7 days after being discharged, citing expense as a reason. Treatment with olanzapine did not fully remit the symptoms and it was ceased.
Because there was no improvement by seventh day, he was restarted on buprenorphine 2 mg twice a day after which his psychotic symptoms were observed to completely remit within the next 48 hours. He is being followed up and has had no recurrence of psychotic symptoms for the last 6 months while continuing to be on a tapering dose of buprenorphine (currently at 4 mg).
DISCUSSION Supersensitivity psychosis after discontinuation or reduction of antipsychotic treatment9,10 has been well recognized because of dopaminergic supersensitivity and rebound,10 psychological reaction to the withdrawal,9 or a genuine relapse of a preexisting condition.9 It is possible that buprenorphine prompted a partial agonist action on the 5-HT2a receptors in the ventral tegmental area and, through an indirect effect, may have led to an increased glutamate release in the prefrontal cortex, anterior cingulate cortex, and putamen leading to acute psychotic effects.11 Another possibility is that buprenorphine, with its moderate antipsychotic effects due to its kappa antagonism,6 may have unmasked psychotic symptoms due to the sudden cessation. A lack of positive history of other substance use and a family history of psychosis make this case more likely to be related to buprenorphine withdrawal with a remission of the psychotic symptoms after reinstitution of buprenorphine.
AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Praveen Navkhare, MBBS, DNB Regional Mental Hospital Nagpur, Maharashtra India
Gurvinder Kalra, MD Flynn Adult Inpatient Unit La Trobe Regional Hospital (LRH) LRH Mental Health Services (LRH MHS) Traralgon, Victoria, Australia
Journal of Clinical Psychopharmacology • Volume 37, Number 6, December 2017
Sahoo Saddichha, DPM, MD, FAP, FRANZCP, FCP Ipswich Hospital, Queensland Health Brisbane, Australia and School of Medicine, University of Queensland Brisbane, Australia [email protected]
REFERENCES 1. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004;2:395–402. 2. Emrich HM, Vogt P, Herz A. Possible antidepressive effects of opioids: action of buprenorphine. Ann N Y Acad Sci. 1982;398: 108–112. 3. Jagadheesan K, Muirhead D. Possible manic potential of buprenorphine. Aust N Z J Psychiatry. 2004;38:560–561. 4. Varma S, Balachander S, Basu D. Buprenorphine-induced psychotic symptoms: a case report. Prim Care Companion CNS Disord. 2013;15: PCC.13l01522. 5. Saddichha S, Subodh BN, Chand PK. Sublingual buprenorphine-induced psychomimetic effects. Am J Ther. 2016;23: e242–e243. 6. Schmauss C, Yassouridis A, Emrich HM. Antipsychotic effect of buprenorphine in schizophrenia. Am J Psychiatry. 1987;144: 1340–1342. 7. Weibel S, Mallaret M, Bennouna-Greene M, et al. A case of acute psychosis after buprenorphine withdrawal: abrupt versus progressive discontinuation could make a difference. J Clin Psychiatry. 2012;73:e756. 8. Karila L, Berlin I, Benyamina A, et al. Psychotic symptoms following buprenorphine withdrawal. Am J Psychiatry. 2008;165: 400–401. 9. Moncrieff J. Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem. Med Hypotheses. 2006;67:517–523. 10. Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry. 1997; 58:252–255. 11. Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101:131–181.
www.psychopharmacology.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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Possible Psychosis Associated With Buprenorphine Withdrawal To the Editors: uprenorphine is widely used in managing opioid dependence and is primarily a partial mu agonist and kappa antagonist at the opioid receptors.1 Buprenorphine also has possible effects on mood.2,3 In addition, buprenorphine has been reported to both cause psychosis4,5 and have possible antipsychotic6 properties. Only 2 earlier instances of acute psychosis caused after buprenorphine withdrawal7,8 have been reported, which, however, also had a history of psychosis and comorbid polysubstance use. We are reporting the third case of possible buprenorphine withdrawal–associated acute psychosis in a patient with no history and no other substance misuse.
B
CASE REPORT A 40-year-old man brought for management of opioid withdrawal symptoms was treated with buprenorphine 16 mg administered during a 2-week inpatient setting, with regular ongoing monitoring of his withdrawal and mental state. He had no history of any other psychiatric illness or use of other substances, with the exception of opioids. On review in the second week after discharge, his wife reported a significant change in his behavior. Mental state assessment revealed clear referential and persecutory delusions along with accompanying visual hallucinations. There was no evidence of delirium and his sensorium was normal. There were no clinical signs or symptoms of opioid withdrawal. All routine investigations including neuroimaging (computed tomography of the brain) at this time showed normal results. Urine drug screen was negative for any other substance. He had no family history of any psychiatric illness including any psychotic spectrum disorders. On further probing, it was found that the client had abruptly stopped buprenorphine 7 days after being discharged, citing expense as a reason. Treatment with olanzapine did not fully remit the symptoms and it was ceased.
Because there was no improvement by seventh day, he was restarted on buprenorphine 2 mg twice a day after which his psychotic symptoms were observed to completely remit within the next 48 hours. He is being followed up and has had no recurrence of psychotic symptoms for the last 6 months while continuing to be on a tapering dose of buprenorphine (currently at 4 mg).
DISCUSSION Supersensitivity psychosis after discontinuation or reduction of antipsychotic treatment9,10 has been well recognized because of dopaminergic supersensitivity and rebound,10 psychological reaction to the withdrawal,9 or a genuine relapse of a preexisting condition.9 It is possible that buprenorphine prompted a partial agonist action on the 5-HT2a receptors in the ventral tegmental area and, through an indirect effect, may have led to an increased glutamate release in the prefrontal cortex, anterior cingulate cortex, and putamen leading to acute psychotic effects.11 Another possibility is that buprenorphine, with its moderate antipsychotic effects due to its kappa antagonism,6 may have unmasked psychotic symptoms due to the sudden cessation. A lack of positive history of other substance use and a family history of psychosis make this case more likely to be related to buprenorphine withdrawal with a remission of the psychotic symptoms after reinstitution of buprenorphine.
AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Praveen Navkhare, MBBS, DNB Regional Mental Hospital Nagpur, Maharashtra India
Gurvinder Kalra, MD Flynn Adult Inpatient Unit La Trobe Regional Hospital (LRH) LRH Mental Health Services (LRH MHS) Traralgon, Victoria, Australia
Journal of Clinical Psychopharmacology • Volume 37, Number 6, December 2017
Sahoo Saddichha, DPM, MD, FAP, FRANZCP, FCP Ipswich Hospital, Queensland Health Brisbane, Australia and School of Medicine, University of Queensland Brisbane, Australia [email protected]
REFERENCES 1. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004;2:395–402. 2. Emrich HM, Vogt P, Herz A. Possible antidepressive effects of opioids: action of buprenorphine. Ann N Y Acad Sci. 1982;398: 108–112. 3. Jagadheesan K, Muirhead D. Possible manic potential of buprenorphine. Aust N Z J Psychiatry. 2004;38:560–561. 4. Varma S, Balachander S, Basu D. Buprenorphine-induced psychotic symptoms: a case report. Prim Care Companion CNS Disord. 2013;15: PCC.13l01522. 5. Saddichha S, Subodh BN, Chand PK. Sublingual buprenorphine-induced psychomimetic effects. Am J Ther. 2016;23: e242–e243. 6. Schmauss C, Yassouridis A, Emrich HM. Antipsychotic effect of buprenorphine in schizophrenia. Am J Psychiatry. 1987;144: 1340–1342. 7. Weibel S, Mallaret M, Bennouna-Greene M, et al. A case of acute psychosis after buprenorphine withdrawal: abrupt versus progressive discontinuation could make a difference. J Clin Psychiatry. 2012;73:e756. 8. Karila L, Berlin I, Benyamina A, et al. Psychotic symptoms following buprenorphine withdrawal. Am J Psychiatry. 2008;165: 400–401. 9. Moncrieff J. Why is it so difficult to stop psychiatric drug treatment? It may be nothing to do with the original problem. Med Hypotheses. 2006;67:517–523. 10. Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry. 1997; 58:252–255. 11. Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101:131–181.
www.psychopharmacology.com
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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