Skip to main content

The Role of Opiates in Social Pain and Suicidal Behavior

Part of the Current Topics in Behavioral Neurosciences book series (CTBN,volume 46)

Abstract

With more than 800,000 deaths by suicide each year and 20 to 30 times more suicide attempts worldwide, suicide is a major public health problem. Current treatments of SB are mainly based on pharmacological treatments that are not specific of SB (e.g. antidepressants), and new therapeutic targets are urgently needed. Recent data strengthen the ancient conception pain (social, psychic, physical) that is at the core of the suicidal process and should be incorporated in the clinical assessment of suicide risk. Then, the mechanisms involved in the regulation of pain may open new avenues regarding therapeutic perspectives. Opiates appear to be a promising candidate in treatment of SB. Indeed, since the last two decades, growing evidences suggest an implication of the opioid system in the pathophysiology of SB, this conduct to the elaboration of randomized controlled trials (RCTs) using opiates in patients with SB. Results suggesting an anti-suicidal effect of buprenorphine and the potential opioidergic-related anti-suicidal effect of ketamine both contribute to the growing interest in opiates use in SB. In this review, we will summarize a large part of the evidence that leads researchers and clinicians to be interested in the use of opiates for SB treatment and discuss on new opioid pharmacological options for suicidal patients.

Keywords

  • Opiates
  • Opioid system
  • Pain
  • Suicidal behavior
  • Therapeutics

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/7854_2020_167
  • Chapter length: 14 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   149.00
Price excludes VAT (USA)
  • ISBN: 978-3-030-57574-8
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   199.99
Price excludes VAT (USA)
Hardcover Book
USD   199.99
Price excludes VAT (USA)

References

  • Ahmadi J, Jahromi MS, Ehsaei Z (2018) The effectiveness of different singly administered high doses of buprenorphine in reducing suicidal ideation in acutely depressed people with co-morbid opiate dependence: a randomized, double-blind, clinical trial. Trials 19:462

    PubMed  PubMed Central  Google Scholar 

  • Apkarian AV, Bushnell MC, Treede R-D, Zubieta J-K (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain Lond Engl 9:463–484

    Google Scholar 

  • Arias AJ, Chan G, Gelernter J, Farrer L, Kranzler HR (2012) Variation in OPRM1 and risk of suicidal behavior in drug-dependent individuals. Am J Addict 21:5–10

    PubMed  Google Scholar 

  • Berrettini W (2016) Alcohol addiction and the mu-opioid receptor. Prog Neuro-Psychopharmacol Biol Psychiatry 65:228–233

    CAS  Google Scholar 

  • Bershad AK, Seiden JA, de Wit H (2016) Effects of buprenorphine on responses to social stimuli in healthy adults. Psychoneuroendocrinology 63:43–49

    CAS  PubMed  Google Scholar 

  • Bertoletti E, Zanoni A, Giorda R, Battaglia M (2012) Influence of the OPRM1 gene polymorphism upon children’s degree of withdrawal and brain activation in response to facial expressions. Dev Cogn Neurosci 2:103–109

    PubMed  Google Scholar 

  • Bilkei-Gorzo A et al (2008) Control of hormonal stress reactivity by the endogenous opioid system. Psychoneuroendocrinology 33:425–436

    CAS  PubMed  Google Scholar 

  • Bohnert ASB, Ilgen MA (2019) Understanding links among opioid use, overdose, and suicide. N Engl J Med 380:71–79

    PubMed  Google Scholar 

  • Bonenberger M, Plener PL, Groschwitz RC, Grön G, Abler B (2015) Polymorphism in the μ-opioid receptor gene (OPRM1) modulates neural processing of physical pain, social rejection and error processing. Exp Brain Res 233:2517–2526

    CAS  PubMed  Google Scholar 

  • Cacioppo S et al (2013) A quantitative meta-analysis of functional imaging studies of social rejection. Sci Rep 3:1–3

    Google Scholar 

  • Calati R, Courtet P (2016) Is psychotherapy effective for reducing suicide attempt and non-suicidal self-injury rates? Meta-analysis and meta-regression of literature data. J Psychiatr Res 79:8–20

    PubMed  Google Scholar 

  • Canuso CM et al (2018) Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry 175:620–630

    PubMed  Google Scholar 

  • Choi CY (2016) Chronic pain and opiate management. Dis Mon 62:334–345

    PubMed  Google Scholar 

  • Chou W-Y et al (2006) Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 105:334–337

    CAS  PubMed  Google Scholar 

  • Conejero I, Olié E, Calati R, Ducasse D, Courtet P (2018) Psychological pain, depression, and suicide: recent evidences and future directions. Curr Psychiatry Rep 20:33

    PubMed  Google Scholar 

  • Courtet P, Olié É (2014) Antidepressants do prevent suicide, at least pending something better. Bull Acad Natl Méd 198:881–892

    PubMed  Google Scholar 

  • Courtet P, Olié E (2019) Social pain at the core of suicidal behavior. L’Encephale 45(Suppl 1):S7–S12

    PubMed  Google Scholar 

  • Dalgleish T et al (2017) Social pain and social gain in the adolescent brain: a common neural circuitry underlying both positive and negative social evaluation. Sci Rep 7:42010

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dean AJ, Bell J, Mascord DJ, Parker G, Christie MJ (2002) A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms. J Affect Disord 72:85–90

    CAS  PubMed  Google Scholar 

  • Dean A, Bell J, Christie M, Mattick R (2004) Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence. Eur Psychiatry 19:510–513

    PubMed  Google Scholar 

  • Demidenko MI et al (2017) Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. Gen Hosp Psychiatry 47:29–35

    PubMed  Google Scholar 

  • DeWall CN et al (2012) Do neural responses to rejection depend on attachment style? An fMRI study. Soc Cogn Affect Neurosci 7:184–192

    PubMed  Google Scholar 

  • Drolet G et al (2001) Role of endogenous opioid system in the regulation of the stress response. Prog Neuro-Psychopharmacol Biol Psychiatry 25:729–741

    CAS  Google Scholar 

  • Ducasse D et al (2018a) Acceptance and commitment therapy for the management of suicidal patients: a randomized controlled trial. Psychother Psychosom 87:211–222

    PubMed  Google Scholar 

  • Ducasse D et al (2018b) Psychological pain in suicidality: a meta-analysis. J Clin Psychiatry 79:16r10732. https://doi.org/10.4088/JCP.16r10732

    CrossRef  PubMed  Google Scholar 

  • Ehrich E et al (2015) Evaluation of opioid modulation in major depressive disorder. Neuropsychopharmacology 40:1448–1455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenberger NI (2012) The neural bases of social pain: evidence for shared representations with physical pain. Psychosom Med 74:126–135

    PubMed  PubMed Central  Google Scholar 

  • Eisenberger NI, Lieberman MD, Williams KD (2003) Does rejection hurt? An FMRI study of social exclusion. Science 302:290–292

    CAS  PubMed  Google Scholar 

  • Eisenberger NI, Taylor SE, Gable SL, Hilmert CJ, Lieberman MD (2007) Neural pathways link social support to attenuated neuroendocrine stress responses. NeuroImage 35:1601–1612

    PubMed  PubMed Central  Google Scholar 

  • Eisenberger NI et al (2011) Attachment figures activate a safety signal-related neural region and reduce pain experience. Proc Natl Acad Sci 108:11721–11726

    CAS  PubMed  Google Scholar 

  • Falcon E, Maier K, Robinson SA, Hill-Smith TE, Lucki I (2015) Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology 232:907–915

    CAS  PubMed  Google Scholar 

  • Falcon E et al (2016) Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology. https://doi.org/10.1038/npp.2016.38

  • Fava M et al (2016) Opioid modulation with buprenorphine/Samidorphan as adjunctive treatment for inadequate response to antidepressants: a randomized double-blind placebo-controlled trial. Am J Psychiatry 173:499–508

    PubMed  Google Scholar 

  • Foster T (2011) Adverse life events proximal to adult suicide: a synthesis of findings from psychological autopsy studies. Arch Suicide Res 15:1–15

    PubMed  Google Scholar 

  • Gabilondo AM, Meana JJ, García-Sevilla JA (1995) Increased density of mu-opioid receptors in the postmortem brain of suicide victims. Brain Res 682:245–250

    CAS  PubMed  Google Scholar 

  • Gassaway MM, Rives M-L, Kruegel AC, Javitch JA, Sames D (2014) The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Transl Psychiatry 4:e411

    CAS  PubMed  PubMed Central  Google Scholar 

  • Greden JF (2001) The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry 62(Suppl 22):5–9

    PubMed  Google Scholar 

  • Gross-Isseroff R, Dillon KA, Israeli M, Biegon A (1990) Regionally selective increases in mu opioid receptor density in the brains of suicide victims. Brain Res 530:312–316

    CAS  PubMed  Google Scholar 

  • Gupta A, Devi LA, Gomes I (2011) Potentiation of μ-opioid receptor-mediated signaling by ketamine: opioid-ketamine interactions. J Neurochem 119:294–302

    CAS  PubMed  Google Scholar 

  • Halbreich U, Endicott J (1981) Possible involvement of endorphin withdrawal or imbalance in specific premenstrual syndromes and postpartum depression. Med Hypotheses 7:1045–1058

    CAS  PubMed  Google Scholar 

  • Herman BH, Panksepp J (1981) Ascending endorphin inhibition of distress vocalization. Science 211:1060–1062

    CAS  PubMed  Google Scholar 

  • Hishimoto A et al (2008) A functional polymorphism of the micro-opioid receptor gene is associated with completed suicides. J Neural Transm 115:531–536

    CAS  PubMed  Google Scholar 

  • Hsu DT et al (2013) Response of the μ-opioid system to social rejection and acceptance. Mol Psychiatry 18:1211–1217

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu DT et al (2015) It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Mol Psychiatry 20:193–200

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hurd YL (2002) Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex. Mol Psychiatry 7:75–81

    CAS  PubMed  Google Scholar 

  • Hurd YL et al (1997) Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects. Mol Psychiatry 2:495–500

    CAS  PubMed  Google Scholar 

  • Icick R et al (2014) OPRM1 polymorphism and lifetime suicide attempts among stabilized, methadone-maintained outpatients. Psychiatry Res 218:259–260

    CAS  PubMed  Google Scholar 

  • Ilgen MA et al (2016) Opioid dose and risk of suicide. Pain 157:1079–1084

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kalin NH, Shelton SE, Barksdale CM (1988) Opiate modulation of separation-induced distress in non-human primates. Brain Res 440:285–292

    CAS  PubMed  Google Scholar 

  • Karp JF et al (2014) Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry 75:e785–e793

    PubMed  PubMed Central  Google Scholar 

  • Kennedy SE, Koeppe RA, Young EA, Zubieta J-K (2006) Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry 63:1199–1208

    CAS  PubMed  Google Scholar 

  • Klein JW (2016) Pharmacotherapy for substance use disorders. Med Clin North Am 100:891–910

    PubMed  Google Scholar 

  • Kroslak T et al (2007) The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J Neurochem 103:77–87

    CAS  PubMed  Google Scholar 

  • Kross E, Berman MG, Mischel W, Smith EE, Wager TD (2011) Social rejection shares somatosensory representations with physical pain. Proc Natl Acad Sci U S A 108:6270–6275

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kubica-Cielińska A, Zielińska M (2015) The use of nalbuphine in paediatric anaesthesia. Anaesthesiol Intensive Ther 47:252–256

    PubMed  Google Scholar 

  • Lovallo WR et al (2012) Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: studies from the Oklahoma family health patterns project. Psychoneuroendocrinology 37:1922–1928

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lovallo WR et al (2015) Cortisol stress response in men and women modulated differentially by the Mu-opioid receptor gene polymorphism OPRM1 A118G. Neuropsychopharmacology 40:2546–2554

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lutz P-E, Mechawar N, Turecki G (2017) Neuropathology of suicide: recent findings and future directions. Mol Psychiatry 22:1395–1412

    PubMed  Google Scholar 

  • Lutz P-E, Courtet P, Calati R (2018a) The opioid system and the social brain: implications for depression and suicide. J Neurosci Res. https://doi.org/10.1002/jnr.24269

  • Lutz P-E et al (2018b) Epigenetic regulation of the kappa opioid receptor by child abuse. Biol Psychiatry 84:751–761

    CAS  PubMed  Google Scholar 

  • Lutz P-E, Almeida D, Belzeaux R, Yalcin I, Turecki G (2018c) Epigenetic regulation of the kappa opioid receptor gene by an insertion-deletion in the promoter region. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol 28:334–340

    CAS  Google Scholar 

  • Mague SD, Blendy JA (2010) OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug Alcohol Depend 108:172–182

    CAS  PubMed  PubMed Central  Google Scholar 

  • Masten CL et al (2011) Subgenual anterior cingulate responses to peer rejection: a marker of adolescents’ risk for depression. Dev Psychopathol 23:283–292

    PubMed  PubMed Central  Google Scholar 

  • Masten CL, Telzer EH, Fuligni AJ, Lieberman MD, Eisenberger NI (2012) Time spent with friends in adolescence relates to less neural sensitivity to later peer rejection. Soc Cogn Affect Neurosci 7:106–114

    PubMed  Google Scholar 

  • Meerwijk EL, Weiss SJ (2014) Toward a unifying definition: response to ‘the concept of mental pain’. Psychother Psychosom 83:62–63

    PubMed  Google Scholar 

  • Meerwijk EL, Weiss SJ (2018) Tolerance for psychological pain and capability for suicide: contributions to suicidal ideation and behavior. Psychiatry Res 262:203–208

    PubMed  PubMed Central  Google Scholar 

  • Meyer ML, Williams KD, Eisenberger NI (2015) Why social pain can live on: different neural mechanisms are associated with reliving social and physical pain. PLoS One 10:e0128294

    PubMed  PubMed Central  Google Scholar 

  • Nobile B et al (2018) Tianeptine is associated with lower risk of suicidal ideation worsening during the first weeks of treatment onset compared with other antidepressants: a naturalistic study. J Psychiatr Res 96:167–170

    CAS  PubMed  Google Scholar 

  • Nobile B et al (2019) Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients. Sci Rep 9:2569

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Connor DB, Ferguson E, Green JA, O’Carroll RE, O’Connor RC (2016) Cortisol levels and suicidal behavior: a meta-analysis. Psychoneuroendocrinology 63:370–379

    PubMed  Google Scholar 

  • Olié E, Guillaume S, Jaussent I, Courtet P, Jollant F (2010) Higher psychological pain during a major depressive episode may be a factor of vulnerability to suicidal ideation and act. J Affect Disord 120:226–230

    PubMed  Google Scholar 

  • Olié E et al (2013) History of suicidal behaviour and analgesic use in community-dwelling elderly. Psychother Psychosom 82:341–343

    PubMed  Google Scholar 

  • Olié E et al (2017) The experience of social exclusion in women with a history of suicidal acts: a neuroimaging study. Sci Rep 7:89

    PubMed  PubMed Central  Google Scholar 

  • Panksepp J, Bean NJ, Bishop P, Vilberg T, Sahley TL (1980a) Opioid blockade and social comfort in chicks. Pharmacol Biochem Behav 13:673–683

    CAS  PubMed  Google Scholar 

  • Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG (1980b) Endogenous opioids and social behavior. Neurosci Biobehav Rev 4:473–487

    CAS  PubMed  Google Scholar 

  • Perini I et al (2018) The salience of self, not social pain, is encoded by dorsal anterior cingulate and insula. Sci Rep 8:1–9

    CAS  Google Scholar 

  • Peyron R, Laurent B, García-Larrea L (2000) Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin Clin Neurophysiol 30:263–288

    CAS  Google Scholar 

  • Rizvi SJ, Iskric A, Calati R, Courtet P (2017) Psychological and physical pain as predictors of suicide risk: evidence from clinical and neuroimaging findings. Curr Opin Psychiatry 30:159–167

    PubMed  Google Scholar 

  • Rogachov A, Cheng JC, DeSouza DD (2015) Discriminating neural representations of physical and social pains: how multivariate statistics challenge the “shared representation” theory of pain. J Neurophysiol 114:2558–2560

    CAS  PubMed  PubMed Central  Google Scholar 

  • Samuels BA et al (2017) The behavioral effects of the antidepressant tianeptine require the Mu-opioid receptor. Neuropsychopharmacology 42:2052–2063

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scherrer JF et al (2015) Change in opioid dose and change in depression in a longitudinal primary care patient cohort. Pain 156:348–355

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shneidman ES (1998) The suicidal mind. Oxford University Press, Oxford

    Google Scholar 

  • Sia AT et al (2008) A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 109:520–526

    CAS  PubMed  Google Scholar 

  • Stein DJ, van Honk J, Ipser J, Solms M, Panksepp J (2007) Opioids: from physical pain to the pain of social isolation. CNS Spectr 12(669–670):672–674

    Google Scholar 

  • Tenore PL (2008) Psychotherapeutic benefits of opioid agonist therapy. J Addict Dis 27:49–65

    PubMed  Google Scholar 

  • Tsai AC, Lucas M, Kawachi I (2015) Association between social integration and suicide among women in the United States. JAMA Psychiat 72:987–993

    Google Scholar 

  • Way BM, Taylor SE, Eisenberger NI (2009) Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proc Natl Acad Sci U S A 106:15079–15084

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wilkinson ST et al (2018) The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry 175:150–158

    PubMed  Google Scholar 

  • Williams NR et al (2018) Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry 175:1205–1215

    PubMed  PubMed Central  Google Scholar 

  • Woo C-W et al (2014) Separate neural representations for physical pain and social rejection. Nat Commun 5:1–12

    Google Scholar 

  • Yovell Y et al (2016) Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry 173:491–498

    PubMed  Google Scholar 

  • Zalsman G et al (2005) Postmortem mu-opioid receptor binding in suicide victims and controls. J Neural Transm 112:949–954

    CAS  PubMed  Google Scholar 

  • Zalsman G et al (2016) Suicide prevention strategies revisited: 10-year systematic review. Lancet Psychiatry 3:646–659

    PubMed  Google Scholar 

  • Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W (2005) Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 280:32618–32624

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philippe Courtet .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Verify currency and authenticity via CrossMark

Cite this chapter

Nobile, B., Lutz, PE., Olie, E., Courtet, P. (2020). The Role of Opiates in Social Pain and Suicidal Behavior. In: Baca-Garcia, E. (eds) Behavioral Neurobiology of Suicide and Self Harm. Current Topics in Behavioral Neurosciences, vol 46. Springer, Cham. https://doi.org/10.1007/7854_2020_167

Download citation