Survival, Attachment, and Healing: An Evolutionary Lens on Interventions for Trauma-Related Dissociation

Figures & data

Table 1 Psychotherapy Intervention Studies and Impact on Dissociation

Author, Year (Country)	Study Design	Study Objectives	Population	Sample Size (n); Mean Age [SD or Range]	Intervention	Control	Impact on Dissociation	Measure Used
MINDFULNESS AND BODY-BASED THERAPIES
Millman et al, 2023^Citation62 (UK)	Pre/post design	Effect on D/D, interoceptive awareness, mindfulness, and body vigilance	DDD; recruited worldwide	n=60 (DDD group=31); 33.0 [12.1]	Twelve weeks of daily online BA/DE vs DE alone	Healthy controls	Improved in DDD groups	*CDS
Nidich et al, 2016^Citation63 (USA)	RCT	Effect on perceived stress, trauma related anxiety, depression, sleep, and dissociation symptoms	Male prison inmates	n=181; TM group= 28.6 [7.2]	Five sessions of group TM plus practice	TAU	Improved	Modified TSC
Price, 2005^Citation64 (USA)	RCT	Effect on PTSD symptoms, dissociation, psychological distress, physical symptoms, and body awareness	Women with CSA in therapy	n=24; Median age= 41.0 [26–56]	Eight weeks MABT	Massage +psychotherapy	Improved	*DES
Price, 2006^Citation65 (USA)	RCT; Mixed Methods	Effect on PTSD symptoms, dissociation, psychological distress, and physical symptoms	Women with CSA in therapy	n=8; 38.0 [28–52]	Eight weeks MABT	Waitlist	No change	*DES
Price et al, 2012^Citation66 (USA)	RCT	Effect on symptoms of SUD, PTSD, eating disorder, distress, physical symptoms, dissociation, emotion regulation, bodily connection, and awareness	Recently hospitalized women with SUD	n=46; 39.0 [19–58]	Eight weeks MABT + TAU	TAU: 12-week CBT approach	Improved	*DES
Price et al, 2017^Citation67 (USA)	Pre/post design	Effect on PTSD and dissociative symptoms	Women with chronic PTSD in therapy	n=9; 40.7 [25–55]	Twenty, twice weekly yoga practice	None	Improved	*DES
Schoenberg et al, 2012^Citation68 (UK)	RCT	Effect on DPD and associated depression symptoms	DPD diagnosis and CDS score of >70	n=32; Biofeedback= 36.8 [7.7]	Eight, 20min biofeedback sessions over four weeks	Sham	No change	*DES *CDS
Willy-Gravley et al, 2021^Citation69 (USA)	RCT	Effect on substance relapse, body awareness, dissociation, and emotion regulation	Incarcerated women with substance abuse history	n=114; NR	Six weeks of twice weekly EMBER yoga	Therapeutic Community	Improved	*SBC
CBT, SKILLS-BASED OR PSYCHOEDUCATION (PRESENT-FOCUSED)
Cognitive behavioral based interventions
Davis et al, 2011^Citation70 (USA)	RCT	Effect on chronic nightmares and associated symptoms	Trauma-exposed individuals with nightmares	n=47; 47 [38.5]	Two hours per week for three weeks of ERRT	Waitlist	Improved as a function of time, not ERRT	TSI-Dissociation subscale
Guillen Botella et al, 2021^Citation71 (Spain)	NRCT	Effect on symptoms of BPD, depression, impulsivity, dissociation, anxiety, suicide risk, state-trait anger expression, emotion regulation, resilience, quality of life, and reasons for living	Inpatients with BPD	n=72; 32.1 [8.8]	Manualized DBT vs STEPPS	None	Equally improved in DBT and STEPPS	*DES
Hunter et al, 2005^Citation72 (UK)	Pre/post design	Effect on dissociation, depression, anxiety, and function	DPD outpatients	n=21; 38.0 [12.0]	Four to twelve weeks of CBT	None	Improved	*CDS-S *DES
Klein et al, 2010^Citation73 (Australia)	Pre/post design	Effect on symptoms of PTSD, depression, anxiety, quality of life, dissociation, anger, thought control, treatment credibility and satisfaction, and therapeutic alliance	PTSD	n=22; M= 51.0 [11.0], F= 40.6 [11.7]	Ten weeks of online CBT with asynchronous therapist support	None	Improved	*DES
Sachse et al, 2011^Citation74 (UK)	Pre/post design	Effect on mindfulness, and symptoms of anxiety, depression, dissociation, and impulsiveness	BPD at a specialist clinic	n=22; 39.0 [7.5]	Eight week MBCT group	None	No change	*DES
Schweden et al, 2016^Citation75 (Germany)	RCT	Effect on depersonalization symptoms during an acute social stressor	Social Anxiety Disorder	n=92; CBT= 24.6 [5.2]	Up to 25 CBT sessions	Waitlist and healthy controls	Improved	*CDS
Schweden et al, 2020^Citation76 (Germany)	RCT	Effect on depersonalization in the context of performance anxiety; changes in trait test anxiety, emotion regulation, and depressive symptoms	University students with high levels of test anxiety	n=49; CBT= 26.5 [8.0]	One 4.5 hour group CBT session	Waitlist	Improved	*CDS-S
Skills or psychoeducational interventions
Karatzias et al, 2016^Citation77 (Scotland)	Case series	Effect on subjective well-being, mental health symptoms, function, and PTSD and dissociative symptoms	Women with interpersonal trauma	n=71; 40.4 [10.6]	Eighteen TREM group sessions	None	Improved	*DES
Lubin et al, 1998^Citation78 (USA)	Pre/post design	Effect on PTSD, dissociation, depression, and other general psychiatric symptoms	Women victims/witnesses of serious trauma	n=29; 41.5 [10.5]	Sixteen week Interactional Psychoeducation Group Therapy	None	No change	*DES
Najavits et al, 2013^Citation79 (USA and Canada)	Pre/post design	Effect on PTSD and pathological gambling, and symptoms of anxiety, depression, somatization, substance use disorders, coping skills, and function	PTSD + pathological gambling	n=7; 45.9 [10.6]	Six months of weekly SS (max 25 sessions)	None	Improved dissociation and somatization	TSC-40 BSI-18
Najavits & Johnson et al, 2014^Citation80 (USA)	Pre/post design	Effect on psychiatric symptoms including trauma, coping, aggressive and suicidal behaviors	PTSD + SUD; victims of domestic violence or sexual assault	n=7; 45.1 [10.5]	Seventeen weeks of the Creating Change program	None	Improved	TSC-40
Protopopescu et al, 2022^Citation81 (Canada)	RCT	Effect on cognitive functioning, PTSD, anxiety, and depression, dissociation, and emotion regulation	Current or former military or public safety personnel with PTSD or trauma	n=40; 44.25 [7.5]	Nine weeks of group GMT	TAU	Improved	*MDI
Roe-Sepowitz et al, 2014^Citation82 (USA)	Pre/post design	Effect on trauma symptoms	Incarcerated women with trauma	n=320; 33.8 [9.8]	Twelve weeks of a psychoeducation group	None	Improved	TSI
Rudstam et al, 2022^Citation83 (Sweden)	RCT	Effect on trauma symptoms and associated anxiety, distress, depression, dissociation, and function	Women with PTSD or CPTSD	n=45; 43.7 [9.9]	Twelve weeks of group music and imagery	Waitlist control	No change	*SDQ-5 *DES-Taxon *DES
Zlotnick et al, 1997^Citation84 (USA)	RCT	Effect on PTSD and trauma symptoms; dissociation	Women with PTSD + CSA	n=48; 39.0 [9.6]	Fifteen weeks of affect management group	Waitlist control	Improved	*DES
TRAUMA-FOCUSED THERAPIES (INCLUDES MEMORY PROCESSING)
Trauma focused psychotherapies
Abramowitz et al, 2010^Citation85 (Israel)	Pre/Post design	Effect on PTSD and associated depressive and dissociative symptoms	Military members with PTSD symptoms	n=37; 41.2 [12.2]	Six weekly hypnotherapeutic olfactory conditioning sessions	None	Improved	*DES
Carletto et al, 2018^Citation86 (Italy)	Pre/post design	Effect on relapse and symptoms of PTSD, anxiety, depression, and dissociation	SUD	n=40; EMDR= 32.0 [8]	Twenty-four weeks of EMDR	TAU: addiction specialist, medication	Improved	*DES
Covers et al, 2021^Citation87 (Netherlands)	RCT	Effect on PTSD and associated symptoms of anxiety, depression, and dissociation	PTSD symptoms, recent rape	n=57; 25.8 [8.2]	Two EMDR sessions (3.5 hours total)	TAU	Improved	*DSS
Gonzalez-Vazquez et al, 2018^Citation88 (Spain)	Case-control	Effect on dissociation, general health, and well being	Severe traumatization	n=31; 28.0 [20–59]	Group bilateral stimulation (EMDR-based intervention)	Psychoeducation	No change	*DES
Mauritz et al, 2022^Citation89 (Netherlands)	Pre/post design	Effect on symptoms of PTSD, dissociation, psychiatric symptoms, care needs, quality of life, global functioning, and care consumption	PTSD + severe mental illness and interpersonal trauma	n=23; 49.9 [9.8]	Weekly individual NET (five-sixteen sessions)	None	Improved	*DES
Pabst et al, 2014^Citation90 (Germany)	RCT	Effect on BPD, PTSD, depression, and dissociation symptoms	Women with BPD + chronic PTSD due to rape	n=22; NET= 30.4 [8.6]	Individual weekly or biweekly NET sessions	TAU by BPD experts	Improved	*DES
Rothbaum et al, 2005^Citation91 (USA)	RCT	Effect on PTSD and associated mood, anxiety, SUD, and dissociation symptoms	Women with Chronic PTSD due to rape	n=74; 33.8 [11.0]	Nine bi-weekly PE vs EMDR sessions	Waitlist Control	Improved in PE and EMDR	*DES-II
Combination trauma-focused interventions
Beck et al, 2021^Citation92 (Denmark)	RCT	Effect on trauma symptoms, well-being, somatoform and psychoform dissociation, and attachment	Refugees with personality change after catastrophic experiences or PTSD	n=74; 42.0 [NR]	Sixteen week trauma focused guided music and imagery treatment	TAU: PTSD specific individual psychotherapy	Improved on DSS-20 but not SDQ-20	*SDQ-20*DSS-20
Bowen et al, 2010^Citation93 (Australia)	Pre/post design	Efficacy of disclosure in therapy for reducing anxiety, depression, and frequency and severity of dissociation.	Male military veterans with PTSD enrolled in a PTSD program	n=72; 51.0 [10.4]	PTSD program, encouraged to disclose trauma in group and individual therapy (twenty-four days).	None; comparing high to low trauma disclosure	Improved; disclosures > non-disclosures	CAPS dissociation items
Classen et al, 2001^Citation94 (USA)	RCT	Effect on trauma-related symptoms and associated anxiety, depression, dissociation, sleep, and sexual and interpersonal problems	Women with PTSD due to CSA	n=58; 38.4 [11.7]	Twenty-four weekly trauma focused group vs present focused group	Waitlist	Improved	TSC-40
Cloitre et al, 2012^Citation59 (USA)	RCT	Impact of sequential treatment on dissociation and PTSD symptoms	Women with PTSD related to CSA or physical abuse	n=104; 36.3 [9.7]	Sixteen weeks of either STAIR+ NST, STAIR +SC, or SC/NST	Active control	Improved in all groups; STAIR/NST better for high dissociation group	TSI Dissociation subscale
Görg et al, 2016^Citation95 (Germany)	Pre/post design; mixed methods	Effect on state dissociation and trauma specific emotional experiences	PTSD diagnosis and enrolled in the DBT-PTSD program	n=26; 42.2 [9.4]	Twelve weeks residential DBT-PTSD program plus MORPHEUS two to five times per week.	None	Improved	DSS-4
Harned et al, 2014^Citation96 (USA)	RCT	Effect on PTSD symptoms, NSSI, trauma related guilt cognitions, and symptoms of dissociation, anxiety, and depression	Suicidal and self-injuring women with BPD + PTSD	n=26; 32.6 [12.0]	One year of DBT+PE	DBT without PE	Improved; DBT-PE > DBT	*DES Taxon
Kleindienst et al, 2021^Citation97 (Germany)	RCT	Effect on PTSD and BPD symptoms, NSSI, high-risk behaviors, suicide attempts, dissociative and depressive symptoms, and function	Women with BPD + PTSD	n=93; 33.5 [10.6]	Forty-five weekly sessions of DBT-PTSD vs CPT followed by three booster sessions	Active comparator	Improved in both groups	*DSS
McDonagh et al, 2005^Citation98 (USA)	RCT	Effect on PTSD and associated anxiety, depression, dissociation, hostility, anger symptoms, and quality of life	Women with PTSD + CSA	n=74; CBT=39.8 [9.9], PCT= 39.6 [9.6]	Fourteen weekly sessions of CBT+PE+CR vs PCT	Waitlist	No change in either group	*DES
Raabe et al, 2022^Citation99 (Netherlands)	RCT	Effect on PTSD symptoms and co-occurring depression, dissociation, emotion regulation, shame/guilt, and interpersonal problems	PTSD due to multiple events of childhood abuse (CA-PTSD)	n=61; 35.9 [10.7]	Sixteen trauma ImRs sessions vs 8 STAIR sessions followed by sixteen ImRs	Waitlist control	Improved; ImRs=ImRs/STAIR	*DIS-Q
Steil et al, 2018^Citation100 (Germany)	Pre/post design	Effect on PTSD, BPD, depression, trauma related symptoms, and behavioral dyscontrol difficulties	Women with PTSD related to CSA and ≥ 4 BPD symptoms	n=21; 34.0 [9.3]	Twenty-four weekly DBT-PTSD sessions	None	Improved	*DES
Intensive trauma programs
Steele et al, 2018^Citation101 (USA)	Pre/post design	Effect on PTSD, dissociation, depression symptoms, moral injury, and relational attachment	Military members with PTSD	n=85; 42.9 [11.6]	Seven days (Ten EMDR sessions +equine therapy, yoga, and narrative writing)	None	Improved	*DES
Steuwe et al, 2016^Citation102 (Germany)	Pre/post design	Effect on symptoms of PTSD, BPD, depression, dissociation, and quality of life	Specialty ward inpatients with BPD	n=11; 34.9 [9.7]	Twice weekly NET (four-fifteen sessions); art or music, body therapy and movement	None	Improved	*DES
Zoet et al, 2018^Citation103 (Netherlands)	Pre/post design	Determine the impact of dissociative subtype of PTSD on treatment response	PTSD	n=168; PTSD-DS= 36.1 [11.3], PTSD= 38.8 [10.8]	Eight days of EMDR + PE, physical activity, and group psycho- education	None	Improved	CAPS
Zoet et al, 2021^Citation104 (Netherlands)	Pre/post design	Effect of treatment on PTSD and somatoform dissociative symptoms	PTSD	n=219; 39.7 [12.3]	Eight days of EMDR + PE, physical activity, and group psycho- education	None	Improved	*SDQ-20 *SDQ-5
OTHER PSYCHOTHERAPEUTIC INTERVENTIONS
Damsa et al, 2014^Citation105 (Switzerland)	Pre/post design	Effect on lipid levels in DD as primary focus; effect on general psychiatric symptoms, dissociation, depression, and alliance	DD diagnosis on SCID-IV and DES≥30	n=32; 38.1 [9.8]	Eight weekly psychodynamic therapy sessions	None	Improved	*DES
Gregory et al, 2008^Citation106 (USA)	RCT	Effect on BPD and SUD symptoms, parasuicidal behavior, depression, and dissociation	BPD + Alcohol Use Disorder	n=30; 28.7 [7.7]	Twelve to eighteen weeks psychodynamic group	TAU	Improved	*DES
Hodgdon et al, 2021^Citation107 (USA)	Pre/post design	Effect on PTSD, depression, dissociation, affect dysregulation, somatization, and disrupted self-perception	PTSD + depression; childhood traumas	n=17; 46.0 [NR]	Sixteen weekly internal family systems therapy	None	Improved	SIDES-SR
Kellett et al, 2013^Citation108 (UK)	Case series	Effect on BPD symptoms, distress, identity, and dissociation	BPD diagnosis	n=19; M= 38.0 [1.7], F= 28.3 [8.7]	Twenty-four CAT sessions	None	Improved	*DES
Weiner & McKay, 2013^Citation109 (USA)	Pre/post design	Effect on D/D, anxiety and PTSD symptoms	Undergraduates with high anxiety sensitivity and/or PTSD symptoms	n=352; 20.1 [NR]	Three weekly Interoceptive exposure sessions	None	Improved on DDDS but not DES	*DDDS *DES
Wildgoose et al, 2001^Citation110 (UK)	Case series	Effect on dissociative processes and personality fragmentation in BPD, and general symptomatology	BPD	n=5; 39.4 [7.1]	Sixteen weekly CAT sessions	None	Improved	*DIS-Q

Notes: *Dissociation specific questionnaire.

Abbreviations: BA/DE, Body Awareness and Dance Exercise; BPD, Borderline Personality Disorder; BSI, Brief Symptom Inventory; CAPS, Clinician-Administered PTSD Scale; CAT, Cognitive Analytic Therapy; CBT, Cognitive Behavioral Therapy; CDS-S, Cambridge Depersonalization Scale-Situational; CDS, Cambridge Depersonalization Scale; CPT, Cognitive Processing Therapy; CPTSD, Complex Posttraumatic Stress Disorder; CR, Cognitive Restructuring; CSA, Childhood Sexual Abuse; D/D, Depersonalization/Derealization Symptoms; DBT-PTSD, Dialectical Behavior Therapy for Posttraumatic Stress Disorder; DBT, Dialectical Behavior Therapy; DD, Dissociative Disorder; DDD, Depersonalization Derealization Disorder; DDDS, Degree of Depersonalization and Derealization Scale; DE, Dance Exercise; DES-Taxon, Dissociative Experiences Scale-Taxon; DES, Dissociative Experiences Scale; DIS-Q, Dissociation Questionnaire; DPD, Depersonalization Disorder; DSS, Dissociative Tension Scale; EMBER, Embodied Mindfulness Based Emotional Resilience; EMDR, Eye Movement Desensitization and Reprocessing; ERRT, Exposure, Relaxation, and Rescripting Therapy; F, Female; GMT, Goal Management Training; ImRs, Imagery Rescripting; M, Male; MABT, Mindful Awareness in Body-Oriented Therapy (Formerly “Body-Oriented Therapy”); MBCT, Mindfulness Based Cognitive Therapy; MDI, Multi-Scale Dissociation Inventory; MORPHEUS, A computer program that supports in sensu self-Exposure exercises; n, Sample Size; NET, Narrative Exposure Therapy; NR, Not Reported; NRCT, Non-Randomized Controlled Trial; NSSI, Non-Suicidal Self-Injury; NST, Narrative Story Telling; PCT, Present Centered Therapy; PE, Prolonged Exposure; PTSD-DS, Dissociative Subtype Of Posttraumatic Stress Disorder; PTSD, Posttraumatic Stress Disorder; RCT, Randomized Controlled Trial; SBC, Scale of Body Connectedness; SC, Supportive Counseling; SCID-IV, Structured Clinical Interview for the Diagnostic And Statistical Manual of Mental Disorders-IV; SD, Standard Deviation; SDQ, Somatoform Dissociation Questionnaire; SIDES-SR, Structured Interview for Disorders Of Extreme Stress-Self Report Version; SS, Seeking Safety; STAIR, Skills Training In Affective And Interpersonal Regulation; STEPPS, Systems Training for Emotional Predictability and Problem Solving; SUD, Substance Use Disorder; TAU, Treatment As Usual; TM, Transcendental Meditation; TREM, Trauma Recovery and Empowerment Model; TSC, Trauma Symptom Checklist; TSI, Trauma Symptom Inventory; UK, United Kingdom; USA, United States of America.

Table 2 Medication Intervention Studies and Impact on Dissociation

Author, Year (Country)	Study Design	Study Objective	Population	Sample Size (n); Mean Age [SD or Range]	Medication, Dose, and Treatment Duration	Control	Effect on Dissociation	Dissociation Measure
Bellino et al, 2008^Citation111 (Italy)	Pre/post design	Efficacy and tolerability of adjunctive aripiprazole; BPD, trait impulsiveness, depression, anxiety, social occupational function, and general psychiatric symptoms	BPD + Sertraline non-response (100–200 mg)	n=21; 26.3 [4.6]	Aripiprazole augmentation 10–15 mg/day for 12 weeks	None	Improved	BPDSI
Bozzatello et al, 2017^Citation112 (Italy)	RCT	Efficacy of asenapine compared to olanzapine in BPD; symptoms of BPD, trait impulsiveness, aggression, NSSI, depression, global improvement, and function	BPD from Personality Disorders Clinic	n=51; 24.7 [5.3]	Asenapine (5–10 mg/day) or Olanzapine (5–10 mg/day) for 12 weeks	Comparison of active treatments	Improved	BPDSI
Davis et al, 2004^Citation113 (USA)	RCT	Efficacy of nefazodone for PTSD; monitoring symptoms of PTSD, anxiety, depression, dissociation as well as drug side effects	Chronic PTSD	n=42; 53.8 [8.7]	Nefazodone twice daily for 12 weeks (mean= 435 mg/d; max= 600mg/d)	Placebo	Improved	*CADSS
Hollander et al, 1990^Citation114 (USA)	Case series	Describe cases of DPD or D/D; test if comorbid OCD or PD predicts response to SSRI treatment	DPD or D/D	n=8; 32.14 [10.6]	SSRI at various doses/durations. Fluoxetine (5–80mg/day; n=7) Fluvoxamine (300mg/d; n=1)	None	Improved	Narrative symptom description
Marshall et al, 2007^Citation115 (USA)	RCT	Efficacy of paroxetine on symptoms of PTSD, general psychiatric symptoms, interpersonal problems, anxiety, depression, and dissociation	Chronic PTSD	n=52; 39.8 [11.2]	Paroxetine 60mg/day for 10 weeks	Placebo	Improved	*DES
Marshall et al, 1998^Citation116 (USA)	Pre/post design	Efficacy of paroxetine for symptoms of chronic PTSD, depression, anxiety, dissociative symptoms, and general psychiatric symptoms	Chronic PTSD	n=17; 38.0 [NR]	Paroxetine daily for 12 weeks (mean= 42.5mg/d; max= 60mg/d)	Placebo	Improved	SCL-90 (modified)
Nuller et al, 2001^Citation117 (Russia)	Single blinded cross over design, NRCT	Efficacy of Naloxone for depersonalization symptoms and corticoid secretion	DPD or D/D	n= 50 (naloxone= 14); 32 [NR]	IV naloxone: single dose (1.6–4 mg) or multiple doses (6–50 mg total)	Placebo and healthy volunteer controls for corticoid secretion tests)	Improved	*Depersonalization scale and subjective responses
Philipsen et al, 2004^Citation118 (Germany)	RCT	Effect of clonidine for NSSI urges during acute aversive states	Women with NSSI + BPD in a DBT Program	n=22; 28.7 [6.4]	Clonidine: one 75µ dose and one of 150µg while in an acute state in each participant	No	Improved	*DSS + 20 SDQ items
Philipsen et al, 2004^Citation119 (Germany)	Cross-over RCT	Effect of single dose naloxone for acute dissociative states	Women with BPD	n=9; 34.9 [6.7]	IV naloxone 0.4 mg	Saline placebo	No difference from placebo	*DSS *CADSS
Roullet et al, 2022^Citation120 (France)	RCT	Efficacy of propranolol for reducing PTSD and MDE symptom, comparing high (DES≥30) and low dissociation (DES<30) groups	Chronic PTSD; PCL-5≥45	n=63; 39.2 [35.7–42.1]	Propranolol prior to six weekly NET (0.67 mg/kg then 1.0 mg/kg of long-acting propranolol 90 min later)	Placebo	Improved; propranolol+NET>placebo+NET; greater improvement in DES≥30 group	*DES
Schmahl et al, 2012^Citation121 (Germany)	Two RCT’s; cross over design	Anti-dissociative efficacy of naltrexone compared in highly dissociative BPD.	Women with BPD and DES≥18	n=29; RCT 1= 28.3 [8.0] RCT 2= 29.2 [8.9]	RCT 1: naltrexone 50 mg/day for three weeks RCT 2: naltrexone 50 mg/day or 200mg/day	Placebo	No change	*DSS *DES
Sierra et al, 2003^Citation122 (UK)	RCT; cross over	Effect of Lamotrigine on depersonalization disorder	DPD	n=14; 35.2 [3.4]	Lamotrigine for 6 weeks (max= 250 mg/day)	Placebo	No change	*CDS *DES
Sierra et al, 2006^Citation123 (UK)	Case Series	Effect of Lamotrigine on dissociative symptoms, mainly D/D	DPD in specialty clinic	n=32; 37.1 [18–73]	Lamotrigine: mean 209.8 mg/day (range 25–600 mg/day); 13.7 months (range 6–21 months)	None	Improved on CDS but not DES	*CDS *DES
Simeon et al, 2004^Citation124 (USA)	RCT	Efficacy of fluoxetine for depersonalisation in DPD, symptoms of anxiety, depression, obsessive compulsive disorder, and panic attacks	DPD	n=50; Fluoxetine group= 34.5 [11.4]	Fluoxetine over 10 weeks (max= 60 mg/day)	Placebo	No change	*DSS *DES-DPS
Simeon & Knutelska, 2005^Citation125 (USA)	Case series	Efficacy of naltrexone for depersonalisation in DPD and symptoms of PTSD	DPD	n=14; 30.9 [8.5]	Naltrexone: 100 mg daily for six weeks (n=6); 250 mg daily for 10 weeks (N=7)	None	Improved	*CADSS *DES-DPS *CDS
Uguz & Sahingoz, 2014^Citation126 (Turkey)	Case series	Report on effect of aripiprazole on depersonalization and changes in symptoms of MDD and OCD	Women with DPD + MDD + OCD	n=3; 33.0 [7.0]	Aripiprazole for 6–10 weeks (5 mg/ day and increased to 10 mg/day)	None	Improved	Subjective patient report

Notes: *Dissociation specific measure.

Abbreviations: BPD, Borderline Personality Disorder; BPDSI, Borderline Personality Disorder Severity Index; CADSS, Clinician Administered Dissociative States Scale; CDS, Cambridge Depersonalization Scale; D/D, Depersonalization/Derealization Symptoms; DBT, Dialectical Behavior Therapy; DES-DPS, Dissociative Experiences Scale Depersonalization Subscale; DES, Dissociative Experiences Scale; DPD, Depersonalization Disorder; DSS, Dissociative Tension Scale; IV, Intravenous; MDD, Major Depressive Disorder; MDE, Major Depressive Episode; n, Sample Size; NET, Narrative Exposure Therapy; NR, Not Reported; NRCT, Non-randomized Controlled Trial; NSSI, Non-suicidal Self-Injury; OCD, Obsessive Compulsive Disorder; PCL, Post Traumatic Stress Disorder Checklist; PD, Panic Disorder; PTSD, Post Traumatic Stress Disorder; RCT, Randomized Control Trial; SCL-90, Symptom Checklist-90 Revised; SD, Standard Deviation; SDQ, Somatoform Dissociation Questionnaire; SSRI, Selective Serotonin Reuptake Inhibitor; UK, United Kingdom; USA, United States of America.

Table 3 rTMS Intervention Studies and Impact on Dissociation

Author, Year (Country)	Study Design	Study Objective	Population	Sample Size (n); Mean age, [SD]	Medication, Dose, and Treatment Duration	Control	Effect on Dissociation	Dissociation Measures
Jay et al, 2014^Citation127 (UK)	RCT	Test if low frequency (inhibitory) rTMS to the right VLPFC would decrease autonomic arousal and DPD symptoms	Medication resistant DPD in males	VLPFC: n=8; 34.9 [5.2] TPJ: n=9; 39.3 [14.6]	Single rTMS session; 15 min to right VLPFC or right TPJ at 1 Hz (900 pulses/session)	Healthy controls (n=20)	Improved for both rTMS sites	*CDS
Jay et al, 2016^Citation128 (UK)	Case series	Test rTMS protocol for D/D, depression, and anxiety symptoms	DPD	n=7; 36.1 [12.7]	Twenty rTMS sessions over ten weeks; 15 min to right VLPFC at 1 Hz (900 pulses/session)	No	Improved for CDS; no change in DES	*CDS *DES
Mantovani et al, 2011^Citation129 (USA)	Pre/post design	Test low frequency TPJ rTMS in DPD and associated depression and anxiety symptoms	DPD	n=12; 33.6 [12.9]	Three weeks of right TPJ rTMS (1Hz; 1800 pulses/day), followed by three weeks of either right or left rTMS	No	Improved	*CDS, *CADSS, *DES

Notes: *Dissociation specific measure.

Abbreviations: CADSS, Clinician-Administered Dissociative States Scale; CDS, Cambridge Depersonalization Scale; D/D, Depersonalization/Derealization Symptoms; DES, Dissociative Experiences Scale; DPD, Depersonalization Disorder; n, Sample Size; RCT, Randomized Control Trial; rTMS, repetitive Transcranial Magnetic Stimulation; SD, Standard Deviation; TPJ, Temporoparietal Junction; UK, United Kingdom; USA, United States of America; VLPFC, Ventrolateral Prefrontal Cortex.

Table 4 Dissociation Measures Used in the Included Studies

Measure of Dissociation	Main Focus	Number (%) of References	References
Dissociation specific measures
DES/FDS	State and trait dissociation: D/D, gaps in awareness or memory, identify dissociation	37 (53.6%)	Price, 2005;^Citation64 Price, 2006;^Citation65 Price et al, 2012;^Citation66 Price et al, 2017;^Citation67 Schoenberg et al, 2012;^Citation68 Guillen Botella et al, 2021;^Citation71 Hunter et al, 2005;^Citation72 Klein et al, 2010;^Citation73 Sachse et al, 2011;^Citation74 Karatzias et al, 2016;^Citation77 Lubin et al, 1998;^Citation78 Rudstam et al, 2022;^Citation83 Zlotnick et al, 1997;^Citation84 Abramowitz et al, 2009;^Citation85 Carletto et al, 2018;^Citation86 Gonzalez-Vazquez et al, 2018;^Citation88 Mauritz et al, 2022;^Citation89 Pabst et al, 2014;^Citation90 Rothbaum et al, 2005;^Citation91 Harned et al, 2014;^Citation96 McDonagh et al, 2005;^Citation98 Steil et al, 2018;^Citation100 Steele et al, 2018;^Citation101 Steuwe et al, 2016;^Citation102 Damsa et al, 2014;^Citation105 Gregory et al, 2008;^Citation106 Kellett et al, 2013;^Citation108 Weiner & McKay, 2013;^Citation109 Marshall et al, 2007;^Citation115 Roullet et al, 2022;^Citation120 Schmahl et al, 2012;^Citation121 Sierra et al, 2003;^Citation122 Sierra et al, 2006;^Citation123 Simeon et al, 2004;^Citation124 Simeon & Knutelska, 2005;^Citation125 Jay et al, 2016;^Citation128 Mantovani et al, 2011^Citation129
CDS	State dissociation: D/D	11 (15.9%)	Millman et al, 2023;^Citation62 Schoenberg et al, 2012;^Citation68 Hunter et al, 2005;^Citation72 Schweden et al, 2016;^Citation75 Schweden et al, 2020;^Citation76 Sierra et al, 2003;^Citation122 Sierra et al, 2006;^Citation123 Simeon & Knutelska, 2005;^Citation125 Jay et al, 2014;^Citation127 Jay et al, 2016;^Citation128 Mantovani et al, 2011^Citation129
DSS/DSS-4	State dissociation: D/D, gaps in awareness or memory, sensory alterations	8 (11.9%)	Beck et al, 2021;^Citation92 Covers et al, 2021;^Citation87 Görg et al, 2016;^Citation95 Kleindienst et al, 2021;^Citation97 Philipsen et al, 2004;^Citation118 Philipsen et al, 2004;^Citation119 Schmahl et al, 2012;^Citation121 Simeon et al, 2004^Citation124
SDQ-20/SDQ-5	State and trait dissociation: predominantly somatoform dissociation, also two D/D items	4 (5.8%)	Rudstam et al, 2022;^Citation83 Beck et al, 2021;^Citation92 Zoet et al, 2021;^Citation104 Philipsen et al, 2004^Citation118
CADSS	State dissociation: D/D, identity dissociation, memory gaps	4 (5.8%)	Davis et al, 2004;^Citation113 Philipsen et al, 2004;^Citation119 Simeon & Knutelska, 2005;^Citation125 Mantovani et al, 2011^Citation129
DIS-Q	State and trait dissociation: mainly D/D and identify dissociation, also memory gaps.	2 (2.9%)	Raabe et al, 2022;^Citation99 Wildgoose et al, 2001^Citation110
SBC	State dissociation: awareness and dissociation from bodily sensations, D/D	1 (1.4%)	Willy-Gravley et al, 2021^Citation69
DDDS	Study task-induced state dissociation	1 (1.4%)	Weiner & McKay 2013^Citation109
MDI	State and trait dissociation: D/D, memory gaps, identity dissociation, emotional constriction, disengagement	1 (1.4%)	Protopopescu et al, 2022^Citation81
DS	Depersonalization symptoms	1 (1.4%)	Nuller et al, 2001^Citation117
Subjective report	Participant or clinician report on change in dissociative symptoms	4 (5.8%)	Uguz & Sahingoz, 2014;^Citation126 Nuller et al, 2001;^Citation117 Görg et al, 2016;^Citation95 Hollander et al, 1990^Citation114 (clinician narrative report)
Non-dissociation specific measures
TSC	Trauma symptoms; Three dissociation items pertaining to D/D	4 (5.8%)	Nidich et al, 2016;^Citation63 Najavits et al, 2013;^Citation79 Najavits & Johnson et al, 2014;^Citation80 Classen et al, 2001^Citation94
TSI	PTSD and associated symptoms; Dissociation subscale	3 (4.3%)	Davis et al, 2011;^Citation70 Roe-Sepowitz et al, 2014;^Citation82 Cloitre et al, 2012^Citation59
CAPS	PTSD symptoms; Two dissociation items pertaining to D/D	2 (2.9%)	Bowen et al, 2010;^Citation93 Zoet et al, 2018^Citation103
BPDSI	Borderline personality symptoms; Two dissociation items pertaining to D/D	2 (2.9%)	Bellino et al, 2008;^Citation111 Bozzatello et al, 2017^Citation112
SCL-90	Wide range of psychological symptoms; Dissociation items include: D/D, memory gaps, identity dissociation, and somatic symptoms	1 (1.4%)	Marshall et al, 1998^Citation116
SIDES-SR	Past and current functioning across multiple domains; Two dissociation items: amnesia and transient dissociation/depersonalization.	1 (1.4%)	Hodgdon et al, 2022^Citation107
BSI	Range of psychological symptoms; Somatization as the only dissociative symptom in the scale	1 (1.4%)	Najavits et al, 2013^Citation79

Abbreviations: BPDSI, Borderline personality disorder severity index; BSI; Brief Symptom Inventory; CADSS, Clinician Administered Dissociative states scale; CAPS, Clinician Administered PTSD scale; CDS, Cambridge Depersonalization Scale; D/D, Depersonalization/Derealization symptoms; DDDS, Depersonalization and Derealization Scale; DES/FDS, Dissociative Experiences Scale/ Fragebogen für dissoziative Symptome; DIS-Q, Dissociation questionnaire; DS, Depersonalization Scale; DSS, Dissociative Tension Scale; MDI, Multi-scale dissociation inventory; SBC, Scale of bodily connection; SCL-90, Symptom checklist; SDQ, Somatoform dissociation questionnaire; SIDES-SR, Structured Interview for Disorders of Extreme Stress, Self-report version; TSC, trauma symptom checklist; TSI, Trauma symptom Inventory.

Figure 1 Flow diagram.

Table 5 Pharmacological Interventions Associated with Dissociative Symptom Improvement

Interventions	Number (%) of References	Medication	Reference
Intervention type	16 studies
SSRI	4 (25%)	Paroxetine, Fluoxetine*, Fluvoxamine	Hollander et al, 1990;^Citation114 Marshall et al, 2007;^Citation115 Marshall et al, 1998;^Citation116 Simeon et al, 2004^Citation124
SSRI augmentation	1 (6%)	Aripiprazole + sertraline	Bellino et al, 2008^Citation111
5-HT2 antagonist	1 (6%)	Nefazodone	Davis et al, 2004^Citation113
Atypical antipsychotics	2 (13%)	Asenapine, olanzapine, aripiprazole	Bozzatello et al, 2017;^Citation112 Uguz & Sahingoz, 2014^Citation126
Anticonvulsant	2 (13%)	Lamotrigine*	Sierra et al, 2003;^Citation122 Sierra et al, 2006^Citation123
Opioid antagonists	4 (25%)	Naloxone*, naltrexone*	Nuller et al, 2001;^Citation117 Philipsen et al, 2004;^Citation119 Schmahl et al, 2012;^Citation121 Simeon & Knutelska, 2005^Citation125
α2-adrenergic agonists	1 (6%)	Clonidine	Philipsen et al, 2004^Citation118
Augmentation of exposure therapy	1 (6%)	Propranolol	Roullet et al, 2022^Citation120

Note: *Indicates mixed reports.

Abbreviations: SSRI, Selective Serotonin Reuptake Inhibitor; 5-HT, 5-hydroxytryptamine; α2, Alpha-2.

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