A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial

Zhuoxi Wu, Peng Zhao, Jing Peng, Liang Fang, Jinping Ding, Guangming Yan, Yang Wang, Jing Zhu, Dongting Wang, Yang Li, Zhengqiong Chen, Qingling Zhang, Qiangting Deng, Guangyou Duan, Zhiyi Zuo, Hong Li, Zhuoxi Wu, Peng Zhao, Jing Peng, Liang Fang, Jinping Ding, Guangming Yan, Yang Wang, Jing Zhu, Dongting Wang, Yang Li, Zhengqiong Chen, Qingling Zhang, Qiangting Deng, Guangyou Duan, Zhiyi Zuo, Hong Li

Abstract

Background: Postpartum depression (PPD) is a severe psychiatric disorder. Its risk is associated with the cesarean section (CS). Currently, there are few early intervention strategies for these women with PPD who underwent CS. Methods: This was a parallel-group randomized controlled trial of singleton pregnant women who underwent elective CS in a tertiary referral hospital in China from October, 2017 to September, 2019. After operation, patients received randomly tramadol patient-controlled intravenous analgesia (PCIA; 4 mg/ml; TRA group), hydromorphone PCIA (0.04 mg/ml; HYD group), or ropivacaine patient-controlled epidural analgesia (PCEA; 1.5 mg/ml; ROP group) for 48 h in a 1:1:1 ratio. Total blinding during hospitalization was not feasible due to differences between the PCEA and PCIA treatments. All investigators who performed the follow-up were blinded to the group assignment. Outcomes: A total of 1,230 patients were enrolled for eligibility. Intention-to-treat analysis showed reduced incidence of PPD in the TRA group (n = 27 [6.6%]) than that in the HYD (10.2%, OR 1.62, 95% CI 0.98~2.68; p = 0.059) and ROP groups (10.5%, OR 1.66, 95% CI 1.01~2.75; p = 0.046) at 4 weeks post-operation, however, the difference was not statistically significant (Bonferroni corrected p = 0.118, p = 0.098, respectively). Subgroup analysis in high-risk women (preoperative Edinburgh Postpartum Depression Scale [EPDS] ≥10) showed a significantly lower incidence of PPD in the TRA group (16.5%) than in the HYD (32.6%) and ROP groups (30.9%) (Bonferroni corrected p = 0.022 and p = 0.038, respectively). The per-protocol analysis yielded similar results. Reported adverse events (AEs) were mostly mild. None of the women or infant discontinued treatment due to AEs. Conclusions: Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS. Clinical Trial Registration: https://ichgcp.net/clinical-trials-registry/NCT03309163?term=ETPPD&draw=2&rank=1; ClinicalTrials.gov (NCT03309163).

Keywords: PCIA; cesarean section; perioperative period tramadol PCIA ameliorates PPD 2; postpartum depression; tramadol.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Wu, Zhao, Peng, Fang, Ding, Yan, Wang, Zhu, Wang, Li, Chen, Zhang, Deng, Duan, Zuo and Li.

Figures

Figure 1
Figure 1
Trial flow ITT analyses included all randomized patients in the groups to which they were randomly assigned. A total of 25 patients (2%) (5 in the TRA group, 7 in the HYD group, and 13 in the ROP group) lacked primary outcome data. ITT, Intention-To-Treat, PCIA, Patient-controlled intravenous analgesia, PCEA, Patient-controlled epidural analgesia.
Figure 2
Figure 2
Changes in the incidence of PPD from 4 weeks to 3 months after CS in (A) all patients; and (B) patients at high risk for PPD. P-values were calculated by the χ2 test and adjusted by Bonferroni correction. *p < 0.05 vs. HYD and ROP groups. PPD, Postpartum depression; TRA, Tramadol PCIA; HYD, Hydromorphone PCIA; ROP, Ropivacaine PCEA; CS, cesarean section.
Figure 3
Figure 3
Remission rate at 3 months after CS and proportion of new cases of PPD between 4 weeks and 3 months. The red (2), green (3), and blue (5) short lines on the left of figure represented the subjects suffering from PPD at the 4 weeks after CS, which were lost to follow-up at the 3 months. The lines in the middle of three colors (10, 9, and 17) that followed by dashed lines to the next time point, represented the subjects suffering from PPD at 4 weeks and 3 months after CS. The lines at the bottom of three colors (15, 30, and 21) that marked with solid boxes, represented the subjects suffering from PPD at 4 weeks but remitted at 3 months after CS. The three lines (22, 20, and 14) on the right side of figure that marked with hollow boxes, represented new PPD cases at 3 months after CS. TRA, Tramadol PCIA; HYD, Hydromorphone PCIA; ROP, Ropivacaine PCEA; PPD, Postpartum depression; CS, cesarean section.

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; (2013). 10.1176/appi.books.9780890425596
    1. Munk-Olsen T, Laursen TM, Pedersen CB, Mors O, Mortensen PB. New parents and mental disorders: a population-based register study. JAMA. (2006) 296:2582–9. 10.1001/jama.296.21.2582
    1. Ding G, Niu L, Vinturache A, Zhang J, Lu M, Gao Y, et al. . “Doing the month” and postpartum depression among Chinese women: a Shanghai prospective cohort study. Women Birth. (2020) 33:e151–8. 10.1016/j.wombi.2019.04.004
    1. Siu BW, Leung SS, Ip P, Hung SF, O'Hara MW. Antenatal risk factors for postnatal depression: a prospective study of Chinese women at maternal and child health centres. BMC Psychiatry. (2012) 12:22. 10.1186/1471-244X-12-22
    1. Mao Q, Zhu LX, Su XY. A comparison of postnatal depression and related factors between Chinese new mothers and fathers. J Clin Nurs. (2011) 20:645–52. 10.1111/j.1365-2702.2010.03542.x
    1. Li HT, Hellerstein S, Zhou YB, Liu JM, Blustein J. Trends in cesarean delivery rates in China, 2008-2018. JAMA. (2020) 323:89–91. 10.1001/jama.2019.17595
    1. Molina G, Weiser TG, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Azad T, et al. . Relationship between cesarean delivery rate and maternal and neonatal mortality. JAMA. (2015) 314:2263–70. 10.1001/jama.2015.15553
    1. Xie RH, Lei J, Wang S, Xie H, Walker M, Wen SW. Cesarean section and postpartum depression in a cohort of Chinese women with a high cesarean delivery rate. J Womens Health. (2011) 20:1881–6. 10.1089/jwh.2011.2842
    1. Xu H, Ding Y, Ma Y, Xin X, Zhang D. Cesarean section and risk of postpartum depression: a meta-analysis. J Psychosom Res. (2017) 97:118–26. 10.1016/j.jpsychores.2017.04.016
    1. Goodman JH. Postpartum depression beyond the early postpartum period. J Obstet Gynecol Neonatal Nurs. (2004) 33:410–20. 10.1177/0884217504266915
    1. Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA, National Birth Defects Prevention Study . Specific SSRIs and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ. (2015) 351:h3190. 10.1136/bmj.h3190
    1. Becker M, Weinberger T, Chandy A, Schmukler S. Depression during pregnancy and postpartum. Curr Psychiatry Rep. (2016) 18:32. 10.1007/s11920-016-0664-7
    1. Sockol LE, Epperson CN, Barber JP. A meta-analysis of treatments for perinatal depression. Clin Psychol Rev. (2011) 31:839–49. 10.1016/j.cpr.2011.03.009
    1. Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, et al. . Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. (2018) 392:1058–70. 10.1016/S0140-6736(18)31551-4
    1. Howard LM, Molyneaux E, Dennis CL, Rochat T, Stein A, Milgrom J. Non-psychotic mental disorders in the perinatal period. Lancet. (2014) 384:1775–88. 10.1016/S0140-6736(14)61276-9
    1. Eisenach JC, Pan PH, Smiley R, Lavand'homme P, Landau R, Houle TT. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain. (2008) 140:87–94. 10.1016/j.pain.2008.07.011
    1. Sutton CD, Carvalho B. Optimal pain management after cesarean delivery. Anesthesiol Clin. (2017) 35:107–24. 10.1016/j.anclin.2016.09.010
    1. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. (2000) 60:139–76. 10.2165/00003495-200060010-00008
    1. Duan G, Bao X, Yang G, Peng J, Wu Z, Zhao P, et al. . Patient-controlled intravenous tramadol versus patient-controlled intravenous hydromorphone for analgesia after secondary cesarean delivery: a randomized controlled trial to compare analgesic, anti-anxiety and anti-depression effects. J Pain Res. (2019) 12:49–59. 10.2147/JPR.S184782
    1. Faron-Gorecka A, Kusmider M, Inan SY, Siwanowicz J, Piwowarczyk T, Dziedzicka-Wasylewska M. Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency. Eur J Pharmacol. (2004) 501:103–10. 10.1016/j.ejphar.2004.08.011
    1. Bamigbade TA, Davidson C, Langford RM, Stamford JA. Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. Br J Anaesth. (1997) 79:352–6. 10.1093/bja/79.3.352
    1. Halfpenny DM, Callado LF, Hopwood SE, Bamigbade TA, Langford RM, Stamford JA. Effects of tramadol stereoisomers on norepinephrine efflux and uptake in the rat locus coeruleus measured by real time voltammetry. Br J Anaesth. (1999) 83:909–15. 10.1093/bja/83.6.909
    1. Ilett KF, Paech MJ, Page-Sharp M, Sy SK, Kristensen JH, Goy R, et al. . Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk. Br J Clin Pharmacol. (2008) 65:661–6. 10.1111/j.1365-2125.2008.03117.x
    1. Ito S. Drug therapy for breast-feeding women. N Engl J Med. (2000) 343:118–26. 10.1056/NEJM200007133430208
    1. Caspani O, Reitz MC, Ceci A, Kremer A, Treede RD. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats. Pharmacol Biochem Behav. (2014) 124:290–6. 10.1016/j.pbb.2014.06.018
    1. Ostadhadi S, Norouzi-Javidan A, Chamanara M, Akbarian R, Imran-Khan M, Ghasemi M, et al. . Involvement of NMDA receptors in the antidepressant-like effect of tramadol in the mouse forced swimming test. Brain Res Bull. (2017) 134:136–41. 10.1016/j.brainresbull.2017.07.016
    1. Barber J. Examining the use of tramadol hydrochloride as an antidepressant. Exp Clin Psychopharmacol. (2011) 19:123–30. 10.1037/a0022721
    1. Duan G, Wu Z, Zhao P, Peng J, Chen Z, Zhang Q, et al. . Protocol for a randomised, double-blind, placebo-controlled trial to explore the effect of tramadol in the prevention of postpartum depression (ETPPD). BMJ Open. (2018) 8:e022538. 10.1136/bmjopen-2018-022538
    1. Patton GC, Romaniuk H, Spry E, Coffey C, Olsson C, Doyle LW, et al. . Prediction of perinatal depression from adolescence and before conception (VIHCS):20-year prospective cohort study. Lancet. (2015) 386:875–83. 10.1016/S0140-6736(14)62248-0
    1. Lee DT, Yip SK, Chiu HF, Leung TY, Chan KP, Chau IO, et al. . Detecting postnatal depression in Chinese women. Validation of the Chinese version of the Edinburgh Postnatal Depression Scale. Br J Psychiatry. (1998) 172:433–7. 10.1192/bjp.172.5.433
    1. Tong X, An D, McGonigal A, Park SP, Zhou D. Validation of the Generalized Anxiety Disorder-7 (GAD-7) among Chinese people with epilepsy. Epilepsy Res. (2016) 120:31–6. 10.1016/j.eplepsyres.2015.11.019
    1. He X, Li C, Qian J, Cui H, Wu W. Reliability and validity of a generalized anxiety disorder scale in general hospital outpatients. Shanghai Arch Psychiatry. (2010) 2010:200–3. 10.3969/j.issn.1002-0829.2010.04.002
    1. Wisner KL, Sit DK, McShea MC, Rizzo DM, Zoretich RA, Hughes CL, et al. . Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry. (2013) 70:490–8. 10.1001/jamapsychiatry.2013.87
    1. Postpartum Depression. Action towards C, treatment C: heterogeneity of postpartum depression: a latent class analysis. Lancet Psychiatry. (2015) 2:59–67. 10.1016/S2215-0366(14)00055-8
    1. Boufidou F, Lambrinoudaki I, Argeitis J, Zervas IM, Pliatsika P, Leonardou AA, et al. . CSF and plasma cytokines at delivery and postpartum mood disturbances. J Affect Disord. (2009) 115:287–92. 10.1016/j.jad.2008.07.008
    1. Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, et al. . Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage. (2011) 41:1073–93. 10.1016/j.jpainsymman.2010.08.016
    1. De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt G, Meade M, Outin H. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med. (2000) 26:275–85. 10.1007/s001340051150
    1. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology. (2013) 118:1332–40. 10.1097/ALN.0b013e318289b84b
    1. Bu XS, Zhang J, Zuo YX. Validation of the Chinese version of the quality of recovery-15 score and its comparison with the post-operative quality recovery scale. Patient. (2016) 9:251–9. 10.1007/s40271-015-0148-6
    1. National Collaborating Centre for Mental Health (UK) . Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. Leicester: British Psychological Society; (2014).
    1. Wang SY, Duan KM, Tan XF, Yin JY, Mao XY, Zheng W, et al. . Genetic variants of the kynurenine-3-monooxygenase and postpartum depressive symptoms after cesarean section in Chinese women. J Affect Disord. (2017) 215:94–101. 10.1016/j.jad.2017.03.023
    1. Zhang Z. Variable selection with stepwise and best subset approaches. Ann Transl Med. (2016) 4:136. 10.21037/atm.2016.03.35
    1. Stein A, Pearson RM, Goodman SH, Rapa E, Rahman A, McCallum M, et al. . Effects of perinatal mental disorders on the fetus and child. Lancet. (2014) 384:1800–19
    1. Nakanishi R, Yoshimura M, Suno M, Yamamoto K, Ito H, Uchimine Y, et al. . Detection of dexmedetomidine in human breast milk using liquid chromatography-tandem mass spectrometry: application to a study of drug safety in breastfeeding after Cesarean section. J Chromatogr B Analyt Technol Biomed Life Sci. (2017) 1040:208–13. 10.1016/j.jchromb.2016.11.015
    1. O'Hara MW, Pearlstein T, Stuart S, Long JD, Mills JA, Zlotnick C. A placebo controlled treatment trial of sertraline and interpersonal psychotherapy for postpartum depression. J Affect Disord. (2019) 245:524–32. 10.1016/j.jad.2018.10.361
    1. Faron-Gorecka A, Kusmider M, Inan SY, Siwanowicz J, Dziedzicka-Wasylewska M. Effects of tramadol on alpha2-adrenergic receptors in the rat brain. Brain Res. (2004) 1016:263–7. 10.1016/j.brainres.2004.05.026
    1. Gonzalez AM, Pascual J, Meana JJ, Barturen F, del Arco C, Pazos A, et al. . Autoradiographic demonstration of increased alpha 2-adrenoceptor agonist binding sites in the hippocampus and frontal cortex of depressed suicide victims. J Neurochem. (1994) 63:256–65. 10.1046/j.1471-4159.1994.63010256.x
    1. Ordway GA, Widdowson PS, Smith KS, Halaris A. Agonist binding to alpha 2-adrenoceptors is elevated in the locus coeruleus from victims of suicide. J Neurochem. (1994) 63:617–24. 10.1046/j.1471-4159.1994.63020617.x
    1. Gerrits MM, Vogelzangs N, van Oppen P, van Marwijk HW, van der Horst H, Penninx BW. Impact of pain on the course of depressive and anxiety disorders. Pain. (2012) 153:429–36. 10.1016/j.pain.2011.11.001
    1. Doan L, Manders T, Wang J. Neuroplasticity underlying the comorbidity of pain and depression. Neural Plast. (2015) 2015:504691. 10.1155/2015/504691
    1. Scott DA, Blake D, Buckland M, Etches R, Halliwell R, Marsland C, et al. . A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 microg/mL fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery. Anesth Analg. (1999) 88:857–64. 10.1097/00000539-199904000-00033
    1. Tang NKY, Stella MT, Banks PDW, Sandhu HK, Berna C. The effect of opioid therapy on sleep quality in patients with chronic non-malignant pain. A systematic review and exploratory meta-analysis. Sleep Med Rev. (2019) 45:105–26. 10.1016/j.smrv.2019.03.005
    1. Brennan MJ, Lieberman JA, III. Sleep disturbances in patients with chronic pain: effectively managing opioid analgesia to improve outcomes. Curr Med Res Opin. (2009) 25:1045–55. 10.1185/03007990902797790
    1. Weicker H, Struder HK. Influence of exercise on serotonergic neuromodulation in the brain. Amino Acids. (2001) 20:35–47. 10.1007/s007260170064
    1. Janal MN, Colt EW, Clark WC, Glusman M. Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain. (1984) 19:13–25. 10.1016/0304-3959(84)90061-7
    1. Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev. (2001) 21:33–61. 10.1016/S0272-7358(99)00032-X
    1. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet. (2014) 384:1789–99. 10.1016/S0140-6736(14)61278-2
    1. Heron J, O'Connor TG, Evans J, Golding J, Glover V, Team AS. The course of anxiety and depression through pregnancy and the postpartum in a community sample. J Affect Disord. (2004) 80:65–73. 10.1016/j.jad.2003.08.004
    1. Cicero TJ, Adams EH, Geller A, Inciardi JA, Munoz A, Schnoll SH, et al. . A postmarketing surveillance program to monitor Ultram (tramadol hydrochloride) abuse in the United States. Drug Alcohol Depend. (1999) 57:7–22. 10.1016/S0376-8716(99)00041-1
    1. Cami J, Lamas X, Farre M. Acute effects of tramadol in methadone-maintained volunteers. Drugs. (1994) 47(Suppl. 1):39–43. 10.2165/00003495-199400471-00007
    1. Ko JY, Farr SL, Dietz PM, Robbins CL. Depression and treatment among U.S. pregnant and nonpregnant women of reproductive age, 2005-2009. J Womens Health. (2012) 21:830–6. 10.1089/jwh.2011.3466
    1. Evins GG, Theofrastous JP, Galvin SL. Postpartum depression: a comparison of screening and routine clinical evaluation. Am J Obstet Gynecol. (2000) 182:1080–2. 10.1067/mob.2000.105409
    1. Fergerson SS, Jamieson DJ, Lindsay M. Diagnosing postpartum depression: can we do better? Am J Obstet Gynecol. (2002) 186:899–902. 10.1067/mob.2002.123404
    1. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. (2004) 43:879–923. 10.2165/00003088-200443130-00004
    1. Palmer GM, Anderson BJ, Linscott DK, Paech MJ, Allegaert K. Tramadol, breast feeding, and safety in the newborn. Arch Dis Child. (2018) 103:1110–3. 10.1136/archdischild-2017-313786
    1. Allegaert K, Rochette A, Veyckemans F. Developmental pharmacology of tramadol during infancy: ontogeny, pharmacogenetics, and elimination clearance. Paediatr Anaesth. (2011) 21:266–73. 10.1111/j.1460-9592.2010.03389.x

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