Abstract
Post-traumatic stress disorder (PTSD) is a chronic psychiatric disease resulting from the experience or witnessing of traumatic events. Persistent PTSD symptoms impair patients’ daily quality of life, jeopardizing sleep, mood, sociability, and arousal. Recommended psychological or pharmacological interventions are effective only in a small portion of patients and often lead to relapse. Thus, there is a critical need to address a lack of advancement in the treatment of PTSD. The combination of psychological interventions, aimed at facilitating the extinction of the traumatic memory, and pharmacological medications, represents a promising tool for PTSD treatment. Timely use of psychotherapy in conjunction with pharmacological treatments, rather than monotherapy, could thus determine a synergistic effect by potentiating the effects of psychological interventions. In such a scenario, drugs that modulate cognitive processes involved in the development and/or persistence of post-traumatic symptomatology could be of great help to improve the outcome of psychotherapies and patients' prognosis. The purpose of the present article is to review the current data available from clinical trials on combined pharmacological treatments with psychological interventions in PTSD therapy. An overview of findings from animal studies that prompted clinical research is also discussed.
[http://dx.doi.org/10.1038/nrdp.2015.57] [PMID: 27189040]
[http://dx.doi.org/10.1056/NEJMra1612499] [PMID: 28636846]
[http://dx.doi.org/10.1177/1524838005277438] [PMID: 16237155]
[http://dx.doi.org/10.1177/070674371405900902] [PMID: 25565692]
[http://dx.doi.org/10.1097/YCO.0000000000000167] [PMID: 26001922]
[http://dx.doi.org/10.1176/appi.ajp.162.2.214] [PMID: 15677582]
[http://dx.doi.org/10.3390/bs7010007] [PMID: 28208816]
[http://dx.doi.org/10.1037/amp0000473] [PMID: 31305099]
[http://dx.doi.org/10.4103/0019-5545.117131] [PMID: 24082241]
[http://dx.doi.org/10.1038/npp.2017.162] [PMID: 28745306]
[http://dx.doi.org/10.1016/j.neubiorev.2016.08.023] [PMID: 27590828]
[http://dx.doi.org/10.1007/s00213-018-5086-2] [PMID: 30374892]
[http://dx.doi.org/10.1016/j.neulet.2017.01.006] [PMID: 28065842]
[http://dx.doi.org/10.1037/0022-006X.73.5.953] [PMID: 16287395]
[http://dx.doi.org/10.1037/0022-006X.73.3.515] [PMID: 15982149]
[http://dx.doi.org/10.1080/10503307.2017.1405168] [PMID: 29179647]
[http://dx.doi.org/10.1080/20008198.2020.1729633] [PMID: 32284821]
[http://dx.doi.org/10.1016/j.janxdis.2009.10.011] [PMID: 19962269]
[http://dx.doi.org/10.1186/2045-5380-3-11] [PMID: 23768232]
[http://dx.doi.org/10.1017/s1092852900020526] [PMID: 17192764]
[http://dx.doi.org/10.1111/j.1468-2850.2010.01198.x] [PMID: 26855480]
[http://dx.doi.org/10.1002/da.20803] [PMID: 21394851]
[http://dx.doi.org/10.1186/s12991-020-00283-6] [PMID: 32435270]
[http://dx.doi.org/10.1126/science.287.5451.248] [PMID: 10634773]
[http://dx.doi.org/10.1146/annurev.neuro.21.1.127] [PMID: 9530494]
[http://dx.doi.org/10.1101/cshperspect.a021766] [PMID: 26238360]
[http://dx.doi.org/10.1016/S0959-4388(00)00194-X] [PMID: 11301237]
[http://dx.doi.org/10.1037/0033-2909.96.3.518] [PMID: 6096908]
[http://dx.doi.org/10.1038/nn819] [PMID: 11889468]
[http://dx.doi.org/10.1016/j.brainresbull.2014.04.011] [PMID: 24811207]
[http://dx.doi.org/10.1073/pnas.1301209110] [PMID: 23754441]
[http://dx.doi.org/10.1037/a0026187] [PMID: 22122145]
[PMID: 33840130]
[http://dx.doi.org/10.2174/1389450116666150506114108] [PMID: 25944011]
[http://dx.doi.org/10.1016/S0079-6123(10)82005-9] [PMID: 20541663]
[http://dx.doi.org/10.1038/nrn3138] [PMID: 22127301]
[http://dx.doi.org/10.1523/JNEUROSCI.19-03-01106.1999] [PMID: 9920672]
[http://dx.doi.org/10.1146/annurev.psych.55.090902.142050] [PMID: 14744210]
[http://dx.doi.org/10.1038/nrn1607] [PMID: 15685217]
[http://dx.doi.org/10.1016/j.neuron.2015.09.004] [PMID: 26447570]
[http://dx.doi.org/10.1126/science.160.3827.554] [PMID: 5689415]
[http://dx.doi.org/10.1126/science.159.3811.219] [PMID: 5688702]
[http://dx.doi.org/10.1007/7854_2016_463] [PMID: 27885549]
[http://dx.doi.org/10.1038/35021052] [PMID: 10963596]
[http://dx.doi.org/10.3390/ijms21186580] [PMID: 32916796]
[http://dx.doi.org/10.1016/j.neuron.2011.06.037] [PMID: 21791282]
[http://dx.doi.org/10.1016/S0896-6273(02)01001-2] [PMID: 12408854]
[http://dx.doi.org/10.1016/S0166-2236(02)00042-5] [PMID: 12536129]
[http://dx.doi.org/10.1016/S0896-6273(02)00976-5] [PMID: 12408853]
[http://dx.doi.org/10.1037/0033-2909.86.5.1054] [PMID: 386401]
[http://dx.doi.org/10.1016/j.nlm.2017.07.014] [PMID: 28765085]
[http://dx.doi.org/10.1126/science.1167975] [PMID: 19342552]
[http://dx.doi.org/10.1016/S0896-6273(02)01064-4] [PMID: 12441048]
[http://dx.doi.org/10.5214/ans.0972-7531.1017309] [PMID: 25205891]
[http://dx.doi.org/10.1101/lm.119806] [PMID: 16585797]
[http://dx.doi.org/10.1371/journal.pone.0038849] [PMID: 22768048]
[http://dx.doi.org/10.1523/JNEUROSCI.4100-03.2004] [PMID: 15084662]
[http://dx.doi.org/10.1101/lm.77504] [PMID: 15466300]
[http://dx.doi.org/10.1037/0097-7403.9.3.248] [PMID: 6886630]
[http://dx.doi.org/10.1037/0097-7403.5.4.368] [PMID: 528893]
[http://dx.doi.org/10.1037/0097-7403.1.1.88] [PMID: 1151290]
[http://dx.doi.org/10.1037/0097-7403.28.1.97] [PMID: 11868238]
[http://dx.doi.org/10.1586/ern.11.94] [PMID: 21797656]
[http://dx.doi.org/10.3389/fpsyt.2019.00773] [PMID: 31708821]
[http://dx.doi.org/10.1016/j.cpr.2010.04.007] [PMID: 20546985]
[http://dx.doi.org/10.1523/JNEUROSCI.22-06-02343.2002] [PMID: 11896173]
[http://dx.doi.org/10.1037/0735-7044.110.3.618] [PMID: 8889007]
[http://dx.doi.org/10.1523/JNEUROSCI.21-22-09009.2001] [PMID: 11698611]
[http://dx.doi.org/10.1037/0735-7044.117.2.341] [PMID: 12708530]
[http://dx.doi.org/10.1016/j.biopsych.2005.01.023] [PMID: 15820704]
[http://dx.doi.org/10.1016/j.nlm.2006.12.010] [PMID: 17275356]
[http://dx.doi.org/10.1016/j.nlm.2008.07.003] [PMID: 18672079]
[http://dx.doi.org/10.1523/JNEUROSCI.2466-06.2006] [PMID: 17005868]
[http://dx.doi.org/10.1016/j.nlm.2005.01.001] [PMID: 15820858]
[http://dx.doi.org/10.1001/archpsyc.61.11.1136] [PMID: 15520361]
[http://dx.doi.org/10.1016/j.biopsych.2007.11.011] [PMID: 18179785]
[http://dx.doi.org/10.1111/j.1527-3458.2006.00208.x] [PMID: 17227287]
[http://dx.doi.org/10.1016/j.biopsych.2009.07.036] [PMID: 19811776]
[http://dx.doi.org/10.1016/j.biopsych.2006.12.020] [PMID: 17588545]
[http://dx.doi.org/10.1016/j.biopsych.2006.03.084] [PMID: 16919524]
[PMID: 22346334]
[http://dx.doi.org/10.1037/a0013397] [PMID: 18954211]
[http://dx.doi.org/10.1016/j.jpsychires.2012.05.006] [PMID: 22694905]
[http://dx.doi.org/10.1016/j.biopsych.2012.02.033] [PMID: 22480663]
[http://dx.doi.org/10.1176/appi.ajp.2014.13121625] [PMID: 24743802]
[http://dx.doi.org/10.1089/cap.2013.0106] [PMID: 24506079]
[http://dx.doi.org/10.1038/npp.2013.317] [PMID: 24217129]
[http://dx.doi.org/10.1016/j.janxdis.2019.102149] [PMID: 31698111]
[http://dx.doi.org/10.1016/j.jpsychires.2013.06.020] [PMID: 23870811]
[http://dx.doi.org/10.1016/j.biopsych.2012.12.009] [PMID: 23332511]
[http://dx.doi.org/10.1001/jamanetworkopen.2020.6777] [PMID: 32496566]
[http://dx.doi.org/10.3389/fnbeh.2014.00160] [PMID: 24847228]
[http://dx.doi.org/10.1523/JNEUROSCI.1092-19.2019] [PMID: 31801809]
[http://dx.doi.org/10.1016/j.nlm.2008.06.010] [PMID: 18657626]
[http://dx.doi.org/10.1016/0006-8993(79)90043-X] [PMID: 427586]
[http://dx.doi.org/10.1016/0006-8993(82)90806-X] [PMID: 7127072]
[http://dx.doi.org/10.1523/JNEUROSCI.3248-07.2008] [PMID: 18184779]
[http://dx.doi.org/10.1016/0306-4522(88)90192-3] [PMID: 3252176]
[http://dx.doi.org/10.1126/science.6278591] [PMID: 6278591]
[http://dx.doi.org/10.1101/lm.1079308] [PMID: 18772254]
[http://dx.doi.org/10.1007/s00213-018-5121-3] [PMID: 30656364]
[http://dx.doi.org/10.1111/j.1471-4159.1988.tb01176.x] [PMID: 3141589]
[http://dx.doi.org/10.1002/(SICI)1098-2396(200002)35:2<79:AID-SYN1>3.0.CO;2-X] [PMID: 10611634]
[http://dx.doi.org/10.1007/PL00005243] [PMID: 9750005]
[http://dx.doi.org/10.1016/0091-3057(93)90016-M] [PMID: 8385783]
[http://dx.doi.org/10.1101/lm.71504] [PMID: 15054133]
[http://dx.doi.org/10.1037/0735-7044.121.3.501] [PMID: 17592941]
[http://dx.doi.org/10.1007/s00213-009-1491-x] [PMID: 19242678]
[http://dx.doi.org/10.1101/lm.78804] [PMID: 15466298]
[http://dx.doi.org/10.1037/0097-7403.26.2.174] [PMID: 10782432]
[http://dx.doi.org/10.1037/0022-006X.66.1.185] [PMID: 9489273]
[http://dx.doi.org/10.1016/j.brat.2016.05.002] [PMID: 27183343]
[http://dx.doi.org/10.1002/da.22449] [PMID: 26522237]
[http://dx.doi.org/10.1159/000329454] [PMID: 22116378]
[http://dx.doi.org/10.1016/j.janxdis.2009.01.001] [PMID: 19223151]
[http://dx.doi.org/10.1016/j.tips.2009.10.003] [PMID: 20036429]
[http://dx.doi.org/10.1016/j.biopsych.2013.10.008] [PMID: 24237691]
[http://dx.doi.org/10.1080/16506073.2018.1432679] [PMID: 29448886]
[http://dx.doi.org/10.1001/archpsyc.1984.01790190025003] [PMID: 6742977]
[http://dx.doi.org/10.1176/ajp.144.8.1030] [PMID: 3037926]
[http://dx.doi.org/10.1371/journal.pone.0046585] [PMID: 23056355]
[http://dx.doi.org/10.1016/j.pneurobio.2011.10.007] [PMID: 22067440]
[http://dx.doi.org/10.1016/j.pbb.2003.10.007] [PMID: 14724055]
[http://dx.doi.org/10.1016/j.ejphar.2005.02.001] [PMID: 15792783]
[http://dx.doi.org/10.1101/lm.82404] [PMID: 15466319]
[http://dx.doi.org/10.1016/j.neubiorev.2005.03.019] [PMID: 15925700]
[http://dx.doi.org/10.1016/j.bbr.2005.06.016] [PMID: 16095730]
[http://dx.doi.org/10.1038/s41398-020-00929-9] [PMID: 32694545]
[http://dx.doi.org/10.1016/j.nlm.2006.08.009] [PMID: 17011803]
[http://dx.doi.org/10.1038/srep46071] [PMID: 28397861]
[http://dx.doi.org/10.1176/appi.ajp.2014.13101407] [PMID: 25018057]
[http://dx.doi.org/10.4088/JCP.16m10936] [PMID: 28686823]
[http://dx.doi.org/10.1016/S0959-4388(02)00306-9] [PMID: 12015238]
[http://dx.doi.org/10.1073/pnas.0307803100] [PMID: 14711996]
[http://dx.doi.org/10.1006/nlme.2002.4080] [PMID: 12559837]
[http://dx.doi.org/10.1016/0006-8993(94)91404-4] [PMID: 8069692]
[http://dx.doi.org/10.1186/s12888-014-0232-9] [PMID: 25113244]
[http://dx.doi.org/10.1037/0735-7044.118.2.420] [PMID: 15113269]
[http://dx.doi.org/10.1016/S0306-4530(96)00028-5] [PMID: 9247987]
[http://dx.doi.org/10.1523/JNEUROSCI.3301-04.2005] [PMID: 15647495]
[http://dx.doi.org/10.1016/j.nlm.2006.11.007] [PMID: 17223582]
[http://dx.doi.org/10.1016/j.biopsycho.2006.01.008] [PMID: 16476517]
[http://dx.doi.org/10.1038/npp.2010.184] [PMID: 20962768]
[http://dx.doi.org/10.3389/fnbeh.2013.00214] [PMID: 24421762]
[http://dx.doi.org/10.1523/JNEUROSCI.4163-04.2005] [PMID: 15728847]
[http://dx.doi.org/10.1016/j.neulet.2004.08.046] [PMID: 15519735]
[http://dx.doi.org/10.1016/j.nlm.2011.02.006] [PMID: 21333745]
[http://dx.doi.org/10.1523/JNEUROSCI.2397-06.2006] [PMID: 16971540]
[http://dx.doi.org/10.1038/sj.npp.1300899] [PMID: 16205786]
[http://dx.doi.org/10.1016/j.nlm.2011.06.012] [PMID: 21736945]
[http://dx.doi.org/10.1038/sj.npp.1301215] [PMID: 17047672]
[http://dx.doi.org/10.1007/s00213-018-5116-0] [PMID: 30610352]
[http://dx.doi.org/10.1016/j.yfrne.2009.03.002] [PMID: 19341764]
[http://dx.doi.org/10.1073/pnas.1018214108] [PMID: 21444799]
[http://dx.doi.org/10.1016/j.psyneuen.2014.08.004] [PMID: 25212409]
[http://dx.doi.org/10.3402/ejpt.v1i0.5643] [PMID: 22893802]
[http://dx.doi.org/10.1016/j.janxdis.2018.10.006] [PMID: 30502903]
[http://dx.doi.org/10.1177/2045125312457586] [PMID: 23983983]
[http://dx.doi.org/10.1016/j.tips.2009.07.006] [PMID: 19729208]
[http://dx.doi.org/10.1007/978-3-540-88955-7_3] [PMID: 21104380]
[http://dx.doi.org/10.1016/S0165-6147(00)01482-6] [PMID: 10838609]
[http://dx.doi.org/10.1016/j.nlm.2013.12.010] [PMID: 24382324]
[http://dx.doi.org/10.1038/mp.2012.72] [PMID: 22688188]
[http://dx.doi.org/10.1016/j.nlm.2008.04.003] [PMID: 18486502]
[http://dx.doi.org/10.1016/j.neulet.2005.12.026] [PMID: 16406322]
[http://dx.doi.org/10.1038/npp.2014.103] [PMID: 24801769]
[http://dx.doi.org/10.1177/0269881107083999] [PMID: 18308796]
[http://dx.doi.org/10.1038/ncomms7395] [PMID: 25731744]
[http://dx.doi.org/10.1038/nature00839] [PMID: 12152079]
[http://dx.doi.org/10.1038/npp.2017.305] [PMID: 29265107]
[http://dx.doi.org/10.1111/bph.15341] [PMID: 33314038]
[http://dx.doi.org/10.1038/s41380-018-0215-1] [PMID: 30120421]
[http://dx.doi.org/10.1016/j.biopsych.2019.07.034] [PMID: 31590924]
[http://dx.doi.org/10.1016/j.biopsych.2021.07.019] [PMID: 34598785]
[http://dx.doi.org/10.1016/j.neuropharm.2012.06.063] [PMID: 22796109]
[http://dx.doi.org/10.1111/j.1755-5949.2008.00071.x] [PMID: 19228182]
[http://dx.doi.org/10.1016/j.psyneuen.2014.11.002] [PMID: 25467221]
[http://dx.doi.org/10.1097/JCP.0000000000000180] [PMID: 24987795]
[http://dx.doi.org/10.1007/s40261-014-0212-3] [PMID: 24935052]
[http://dx.doi.org/10.1016/S2215-0366(19)30048-3] [PMID: 30902669]
[http://dx.doi.org/10.1007/s11920-019-1044-x] [PMID: 31161275]
[http://dx.doi.org/10.1016/j.brainresbull.2008.07.007] [PMID: 18722516]
[http://dx.doi.org/10.1186/1471-2210-6-6] [PMID: 16515684]
[http://dx.doi.org/10.1177/0269881117699617] [PMID: 28372480]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05199.x] [PMID: 11085324]
[http://dx.doi.org/10.1007/s00213-017-4650-5] [PMID: 28551715]
[http://dx.doi.org/10.1177/0269881116642542] [PMID: 27118529]
[http://dx.doi.org/10.1016/j.pnpbp.2018.03.003] [PMID: 29524515]
[http://dx.doi.org/10.1038/tp.2015.138] [PMID: 26371762]
[http://dx.doi.org/10.12717/DR.2015.19.2.061] [PMID: 27004262]
[http://dx.doi.org/10.1124/pr.111.005108] [PMID: 22407616]
[http://dx.doi.org/10.5498/wjp.v6.i1.1] [PMID: 27014593]
[http://dx.doi.org/10.1111/j.1601-183X.2012.00801.x] [PMID: 22530815]
[http://dx.doi.org/10.1007/s00213-017-4684-8] [PMID: 28741031]
[http://dx.doi.org/10.1016/j.neuropharm.2012.11.027] [PMID: 23220293]
[http://dx.doi.org/10.1016/j.biopsych.2012.10.012] [PMID: 23260230]
[http://dx.doi.org/10.1038/npp.2015.318] [PMID: 26514583]
[http://dx.doi.org/10.1007/s00213-007-1019-1] [PMID: 18058089]
[http://dx.doi.org/10.1111/j.1469-8986.1991.tb01999.x] [PMID: 1758934]
[http://dx.doi.org/10.1176/appi.ajp.158.1.78] [PMID: 11136637]
[http://dx.doi.org/10.1038/npp.2012.29] [PMID: 22434223]
[http://dx.doi.org/10.1007/s002130050714] [PMID: 9784083]
[http://dx.doi.org/10.1080/20008198.2020.1840123] [PMID: 33408811]
[http://dx.doi.org/10.1007/s00213-020-05710-w] [PMID: 33221932]
[http://dx.doi.org/10.1177/0269881117711712] [PMID: 28635375]
[http://dx.doi.org/10.1016/S2215-0366(18)30135-4] [PMID: 29728331]
[http://dx.doi.org/10.1177/0269881110378371] [PMID: 20643699]
[http://dx.doi.org/10.1177/0269881112456611] [PMID: 23172889]
[http://dx.doi.org/10.1177/0269881112464827] [PMID: 23118021]
[http://dx.doi.org/10.1177/0269881118806297] [PMID: 30371148]
[http://dx.doi.org/10.4103/0259-1162.143110] [PMID: 25886322]
[http://dx.doi.org/10.1007/s00508-017-1299-3] [PMID: 29322377]
[http://dx.doi.org/10.1016/bs.apha.2020.02.005] [PMID: 32616205]
[http://dx.doi.org/10.1176/appi.focus.20180030] [PMID: 31975953]
[http://dx.doi.org/10.1016/j.bbr.2017.04.048] [PMID: 28461010]
[http://dx.doi.org/10.1016/j.nlm.2020.107362] [PMID: 33333316]
[http://dx.doi.org/10.1016/j.bbr.2019.112342] [PMID: 31705920]
[http://dx.doi.org/10.3389/fncel.2017.00100] [PMID: 28473755]
[http://dx.doi.org/10.1016/j.nbd.2016.12.026] [PMID: 28043916]
[http://dx.doi.org/10.1001/jamapsychiatry.2014.62] [PMID: 24740528]
[http://dx.doi.org/10.1016/j.bbapap.2018.03.006] [PMID: 29563072]
[http://dx.doi.org/10.1001/jamanetworkopen.2020.4693] [PMID: 32437573]
[http://dx.doi.org/10.1007/s00213-017-4771-x] [PMID: 29119217]
[http://dx.doi.org/10.1016/S2215-0366(16)30065-7] [PMID: 27210031]
[http://dx.doi.org/10.4088/JCP.v67n1110] [PMID: 17196053]
[http://dx.doi.org/10.1093/ijnp/pyx047] [PMID: 28637246]
[http://dx.doi.org/10.1007/s00213-015-4162-0] [PMID: 26612618]
[http://dx.doi.org/10.1007/s00213-017-4754-y] [PMID: 29085980]
[http://dx.doi.org/10.1002/hbm.23234] [PMID: 27151536]
[http://dx.doi.org/10.1177/0269881111420188] [PMID: 21956378]
[http://dx.doi.org/10.1177/0269881119855974] [PMID: 31294673]
[http://dx.doi.org/10.1021/acschemneuro.8b00134] [PMID: 29664276]
[http://dx.doi.org/10.1007/s00221-013-3579-0] [PMID: 23727882]
[http://dx.doi.org/10.1080/13651501.2019.1699575] [PMID: 31829763]
[http://dx.doi.org/10.3389/fpsyt.2019.00133] [PMID: 30949075]
[http://dx.doi.org/10.1016/j.jad.2017.12.046] [PMID: 29351885]
[http://dx.doi.org/10.3390/brainsci6030028] [PMID: 27517963]
[http://dx.doi.org/10.1016/j.janxdis.2008.03.015] [PMID: 18455908]
[http://dx.doi.org/10.1080/16506073.2015.1012740] [PMID: 25706090]
[http://dx.doi.org/10.1111/ner.12551] [PMID: 27992092]
[http://dx.doi.org/10.1001/jamainternmed.2020.1562] [PMID: 32275292]
[http://dx.doi.org/10.1038/s41380-021-01036-x] [PMID: 33542468]