A systematic review and meta-analysis of psychological interventions for comorbid post-traumatic stress disorder and substance use disorder

Figures & data

Figure 1. Flow diagram of the systematic review. RCT, randomized controlled trial; PTSD, post-traumatic stress disorder; SUD, substance use disorder.

Table 1. Characteristics of the included studies.

Source (country)	Participants and setting	SUD type	Age (years), mean (SD)	Gender	PTSD, alcohol, and substance use outcome measures	Experimental intervention	Control/ comparison intervention(s)	Number of participants, treatment/ control
Acosta et al. (2017) (USA)	Military veterans with PTSD and problematic alcohol misuse recruited from primary care	Alcohol misuse. A subset of participants met diagnosis for AUD	34 (8.1)	93% male; 7% female	PCL-M; TLFB	Web-based self-management programme based on CBT	Primary care TAU	29/32^a
Back et al. (2019) (USA)	Treatment-seeking veterans primarily recruited from newspaper and internet advertisements	Alcohol and substance use disorder	40.4 (10.7)	90.1% male; 9.9% female	CAPS, PCL-M; TLFB, ASI	COPE	Response prevention	54/27
Boden et al. (2014) (USA)	Military veterans recruited from a Veterans Affairs outpatient substance use disorder clinic	Polydrug use	54.0 (9.6)	100% male	IES-R; ASI	Group-based Seeking Safety + TAU	Group-based TAU for SUD	54/55
Capone et al. (2018) (USA)	Military veterans recruited from speciality PTSD, substance use, and returning veteran clinics	Polydrug use	34.2 (8.9)	95.5% male; 4.5% female	CAPS; ASI, TLFB, toxicology	Individual and group integrated CBT for PTSD and SUD + TAU	TAU for SUD	21/23
Coffey et al. (2006) (USA)	Laboratory based: participants recruited from outpatient SUD treatment programmes	Alcohol dependence	37.5 (8.0)	33% male; 67% female	IES-R	Individual trauma-focused exposure therapy + TAU	Imagery-based relaxation + TAU	16/15
Coffey et al. (2016) (USA)	Participants recruited from residential SUD treatment facility	Alcohol dependence and polydrug use	33.7 (10.3)	53.3% male; 46.7% female	CAPS, IES-R; TLFB	Individual trauma-focused exposure therapy + TAU	Healthy lifestyle sessions + TAU	82/38
Foa et al. (2013) (USA)	Treatment-seeking participants recruited by professional referral and advertisement	Alcohol dependence	42.7 (9.7)	65.5% male; 34.5% female	PSS-I; TLFB	Individual PE + supportive counselling^a	Supportive counselling^b	80/85
Frisman et al. (2008) (USA)	Participants recruited from outpatient SUD clinics	Polydrug use	37.5 (8.4)	39.0% male; 61% female	GAIN subscales for substance use frequency, percentage drinking to intoxication, percentage using any drugs, and percentage abusing drugs or alcohol	Group-based coping skill-focused therapy + trauma-sensitive usual care	Trauma-sensitive usual substance use care	119/63^a
Haller et al. (2016) (USA)	Veterans recruited from referrals to an outpatient dual-diagnosis treatment programme	Alcohol or substance dependence	47.26 (11.97)	89% male; 11% female	PCL-C; TLFB	Individual cognitive processing therapy for PTSD and SUD	Individual CBT for SUD and depression only	51/47^a
Hien et al. (2004) (USA)	Outpatients recruited through substance use treatment programmes and advertisement	Polydrug use	36.2 (9.0)	100% female	CAPS, IES-R; SUI, CGI	Individual Seeking Safety + TAU	Relapse prevention + TAU	41/34^c
Hien et al. (2009) (USA)	Outpatients recruited from community-based substance abuse treatment programmes	Polydrug use	39.2 (9.2)	100% female	CAPS, PSS-SR; SUI, toxicology	Group-based Seeking Safety + TAU	Group-based women’s health education + TAU	176/177
Kehle-Forbes et al. (2019) (USA)	Veterans recruited through a variety of channels, including provider referrals and advertisements in veterans’ medical centres	Alcohol or drug abuse. Sample was mainly alcohol dependent	44.1 (16.4)	92.3% male; 7.6% female	PSS-I; TLFB	Phased delivery of motivation enhancement therapy followed by PE	Integrated delivery of motivation enhancement therapy and PE at the same time	88/95
McGovern et al. (2011) (USA)	Participants recruited from community intensive outpatient or methadone maintenance programmes	Polydrug use	37.7 (10.7)	43.4% male; 56.6% female	CAPS; ASI, toxicology	Individual integrated CBT for PTSD and SUD + TAU	Individual addiction counselling + TAU	32/21
McGovern et al. (2015) (USA)	Participants recruited from addiction treatment agencies	Polydrug use, primarily mixed alcohol and opioid use	35.3 (10.4)	40.7% male; 59.3% female	CAPS, PCL-C; TLFB, ASI, toxicology	Individual integrated CBT for PTSD and SUD + TAU	Individual addiction counselling + TAU; TAU only	73/75/73
Mills et al. (2012) (Australia)	Participants recruited from substance use treatment services, advertisement, and practitioner referrals	Substance-dependent polydrug users	33.7 (7.9)	37.9% male; 62.1% female	CAPS; CIDI	COPE + TAU	TAU	55/48
Mueser et al. (2008) (USA)	Individuals with severe mental illness recruited from community mental health centres	Polydrug use. Participants met diagnosis for SUD but not substance dependence	44.2 (10.6)	20.5% male; 79.5% female	CAPS	Individual non-trauma-focused CBT for PTSD	TAU	17/27^a
Myers et al. (2015) (USA)	Participants were victims of IPV recruited through flyers in community agencies serving IPV victims and in primary care and psychiatry clinics	AUD	42.8 (9.3)	100% female	CAPS, PCL-C; TLFB	Adapted group-based Seeking Safety + TAU	12-Step supportive group	31/9
Najavits et al. (2006) (UA)	Outpatient adolescents recruited from local clinics, hospitals, and schools, and through clinicians and posted flyers	Polydrug use. Most participants met diagnosis for substance dependence	16.1 (1.2)	100% female	TSCC; PEI	Individual Seeking Safety + TAU	TAU	18/15
Najavits et al. (2018) (USA)	Veterans recruited through clinicians, flyers, and word of mouth	Polydrug use. Most participants met diagnosis for substance dependence	48.8 (10.8)	73.1% male; 26.9% female	PCL; ASI, toxicology	Individual Creating Change + TAU	Individual Seeking Safety + TAU	26/26
Norman et al. (2019) (USA)	Veterans recruited through veterans’ mental health service clinics	AUD	41.6 (12.6)	89.9% male; 10.1% female	CAPS-5; TLFB	COPE	Seeking Safety	63/56
Possemato et al. (2019) (USA)	Military veterans with PTSD and problematic alcohol misuse recruited from primary care	Alcohol misuse. A subset of participants met diagnosis for AUD	39	93% male; 7% female	PCL-M; TLFB	Peer-supported web-based self-management programme based on CBT	Web-based self-management programme based on CBT	4/6^a
Ruglass et al. (2017) (USA)	Outpatients recruited through advertisements and clinic referrals	Polydrug and alcohol dependence	44.6 (9.3)	63.6% male; 36.4% female	CAPS, MPSS-SR; ASI, SUI	COPE + TAU for SUD	Relapse prevention; activity monitoring	39/43^d
Sannibale et al. (2013) (Australia)	Participants recruited from a range of services and seen on an outpatient basis	AUD	41.2 (11.9)	47% male; 53% female	CAPS, PDS; TLFB, SADQ-C	Individual integrated trauma-focused CBT for PTSD and AUD	CBT for AUD + supportive counselling	33/29
Schacht et al. (2017) (USA)	Participants recruited from an outpatient methadone maintenance clinic	Opioid users with PTSD	37.4 (11.3)	21% male; 79% female	CAPS; ASI	Prolonged exposure + contingency incentives + TAU for SUD	Prolonged exposure + TAU for SUD	28/30
Schäfer et al. (2019) (Germany)	Participants recruited via substance abuse and other psychosocial counselling agencies, substance abuse and mental health clinics, psychotherapists in private practice and in the community	Alcohol and polydrug use	40.9 (11.4)	100% female	PSS-I, PDS; ASI, substance-free days in the past month	Seeking Safety + TAU	Relapse prevention + TAU; TAU only	115/111/117
Stappenbeck et al. (2015) (USA)	Outpatients recruited through newspaper adverts and flyers	Alcohol dependence	44.3 (11.5)	51.3% male; 48.7% female	Adapted version of PCL-C; daily monitoring of number of standard drinks consumed per day	Cognitive restructuring	Experiential acceptance; attention control	31/27/20
Zlotnick et al. (2009) (USA)	Treatment was conducted in a minimum security prison. Participants recruited from a voluntary residential substance abuse treatment programme	Polydrug users. 88% met criteria for alcohol dependence prior to imprisonment	34.6 (7.4)	100% female	CAPS, TSC-40; TLFB, ASI	Group-based Seeking Safety + TAU	TAU	27/22

^a Data were obtained for a subset of participants, from these studies, who met the inclusion criteria for the review.

^b Study used a 2 × 2 design. Participants received experimental and control psychological interventions in combination with naltrexone or a placebo. Data were combined for the psychological intervention arms.

^c We did not include data from a TAU arm, as participants in this group were non-randomized.

^d We did not include data from the activity monitoring arm, owing to significant baseline differences from the other two arms for PTSD and depression.

ASI, Addiction Severity Index; AUD, alcohol use disorder; CAPS, Clinician Administered PTSD Scale; CAPS-5, Clinician Administered PTSD Scale for DSM-5; CBT, cognitive behavioural therapy; CGI, Clinical Global Interview; CIDI, Composite International Diagnostic Interview; COPE, concurrent treatment of PTSD and SUD using PE; GAIN, Global Appraisal of Individual Needs; IES-R, Impact of Events Scale – Revised; IPV, interpersonal violence; MPSS-SR, Modified PTSD Symptom Scale Self-Report; PCL, PTSD Checklist; PCL-C, PTSD Checklist – Civilian Version; PCL-M, PTSD Checklist – Military Version; PDS, Posttraumatic Diagnostic Scale; PE, prolonged exposure; PEI, Personal Experiences Inventory; PSS-I, PTSD Symptom Scale – Interview Version; PSS-SR, PTSD Symptom Scale – Self-Report Version; PTSD, post-traumatic stress disorder; SADQ-C, Severity of Alcohol Dependence Questionnaire; SUD, substance use disorder; SUI, Substance Use Inventory; TAU, treatment as usual; TLFB, Timeline Follow Back; TSCC, Trauma Symptom Checklist for Children; TSC-40, Trauma Symptom Checklist-40.

Table 2. Summary of meta-analysis of results for each comparison for an experimental psychological intervention vs a substance use disorder (SUD)-based or treatment as usual (TAU) control.

Comparison outcome	Follow-up point	Contributing studies	Studies (n)	Sample (n)	RR (95% CI)	SMD (95% CI)	Grade rating
Present-focused treatments + TAU for SUD vs TAU for SUD only
PTSD severity	Post-treatment	Boden et al. (2014), Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	6	814		−0.02 (−0.16, 0.12); I^2 = 0%	Low
	3–5 months	Boden et al. (2014), Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	6	800		−0.01 (−0.15, 0.13); I^2 = 0%	Low
	6–13 months	Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	5	726		0.04 (−0.18, 0.26); I^2 = 40%	Low
PTSD diagnosis	Post-treatment	Myers et al. (2015), Zlotnick et al. (2009)	2	77	1.01 (0.66, 1.54); I^2 = 0%		Very low
Alcohol use	Post-treatment	Boden et al. (2014), Myers et al. (2015), Schäfer et al. (2019)	3	337		−0.21 (−0.67, 0.25); I^2 = 66%	Very low
	3–5 months	Boden et al. (2014), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	4	372		−0.11 (−0.31–0.10); I^2 = 0%	Very low
	6–13 months	Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	3	298		0.44 (−0.43–0.51); I^2 = 58%	Very low
Substance use	Post-treatment	Boden et al. (2014), Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019)	5	765		0.13 (−0.42, 0.16); I^2 = 67%	Very low
	3–5 months	Boden et al. (2014), Frisman et al. (2008), Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	7	925		−0.02 (−0.19–0.15); I^2 = 29%	Low
	6–13 months	Frisman et al. (2008), Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019), Zlotnick et al. (2009)	6	874		−0.00 (−0.13, 0.13); I^2 = 0%	Low
Dropout		Hien et al. (2004, 2009), Myers et al. (2015), Schäfer et al. (2019)	4	694	1.06 (0.92, 1.22); I^2 = 0		Very low
Adverse events		Hien et al. (2009)	1	353	1.03 (0.71, 1.50)		Very low
Trauma-focused treatments + TAU for SUD vs TAU for SUD only
PTSD severity	Post-treatment	Back et al. (2019), Coffey et al. (2006, 2016), Foa et al. (2013), Mills et al. (2012), Ruglass et al. (2017), Sannibale et al. (2013)	7	544		−0.36 (−0.64, −0.08)*; I^2 = 54%	Very low
	3–5 months	Back et al. (2019), Coffey et al. (2016), Ruglass et al. (2017)	3	213		−0.97 (−2.10, 0.16); I^2 = 91%	Very low
	6–13 months	Back et al. (2019), Coffey et al. (2016), Foa et al. (2013), Mills et al. (2012), Sannibale et al. (2013)	5	469		−0.48 (−0.81, −0.15)*; I^2 = 62%	Very low
PTSD diagnosis	Post-treatment	Back et al. (2019), Coffey et al. (2016)	2	201	0.62 (0.46, 0.84)*; I^2 = 30%		Very low
Alcohol use	Post-treatment	Back et al. (2019), Foa et al. (2013), Sannibale et al. (2013)	3	234		0.05 (−0.21, 0.31); I^2 = 0%	Very low
	3–5 months	Back et al. (2019), Coffey et al. (2016)	2	153		−0.07 (−0.41, 0.27); I^2 = 0%	Very low
	6–13 months	Back et al. (2019), Coffey et al. (2016), Foa et al. (2013), Sannibale et al. (2013)	4	363		−0.23 (−0.44, −0.02)*; I^2 = 0%	Very low
Substance use	Post-treatment	Back et al. (2019), Mills et al. (2012), Ruglass et al. (2017)	3	170		0.16 ( −0.63, 0.95); I^2 = 81%	Very low
	3–5 months	Back et al. (2019), Coffey et al. (2016), Ruglass et al. (2017)	3	205		0.09 (−0.28. 0.46); I^2 = 29%	Very low
	6–13 months	Back et al. (2019), Coffey et al. (2016), Mills et al. (2012)	3	256		0.01 (−0.35, 0.38); I^2 = 44%	Very low
Dropout		Back et al. (2019), Coffey et al. (2006, 2016), Foa et al. (2013), Sannibale et al. (2013)	5	459	0.86 (0.71, 1.04); I^2 = 48%		Very low
Adverse events		Back et al. (2019), Foa et al. (2013), Mills et al. (2012), Ruglass et al. (2017), Sannibale et al. (2013)	5	493	0.85 (0.40, 1.82); I^2 = 0%		Very low
ICBT + TAU for SUD vs TAU for SUD only
PTSD severity	Post-treatment	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011, 2015)	4	349		−0.24 (−0.51, 0.03); I^2 = 33%	Very low
	3–5 months	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011)	3	156		−0.12 (−0.44, 0.20); I^2 = 0%	Very low
	6–13 months	McGovern et al. (2011)	1	43		0.07 (0.94, 1.30)	Very low
PTSD diagnosis	Post-treatment	McGovern et al. (2011)	1	53	0.94 (0.68, 1.30)		Very low
Alcohol use	Post-treatment	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011, 2015)	4	352		0.02 (−0.19, 0.24); I^2 = 0	Very low
	3–5 months	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011)	3	165		−0.10 (−0.41, 0.21); I^2 = 0	Very low
	6–13 months	Haller et al. (2016)	1	75		0.19 (−0.27, 0.64)	Very low
Substance use	Post-treatment	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011, 2015)	4	352		−0.08 (−0.30, –0.13); I^2 = 0	Very low
	3–5 months	Capone et al. (2018), Haller et al. (2016), McGovern et al. (2011)	3	165		−0.01 (−0.31, 0.30); I^2 = 0	Very low
	6–13 months	Haller et al. (2016)	1	75		0.19 (−0.27, 0.64)	Very low
Web-based CBT + TAU vs TAU
PTSD severity	Post-treatment	Acosta et al. (2017)	1	49		−0.07 (−0.63, 0.49)	Very low
	3–5 months	Acosta et al. (2017)	1	49		−0.29 (−0.85, 0.28)	Very low
Alcohol use	Post-treatment	Acosta et al. (2017)	1	61		0.11 (−0.39, 0.61)	Very low
	3–5 months	Acosta et al. (2017)	1	61		0.19 (−0.31, 0.69)	Very low
CBT for PTSD vs TAU only
PTSD severity	Post-treatment	Mueser et al. (2008)	1	44		−0.22 (−0.83, 0.39)	Very low
	3–5 months	Mueser et al. (2008)	1	44		−0.25 (−0.86, 0.36)	Very low

CBT, cognitive behavioural therapy; CI, confidence interval; ICBT, integrated cognitive behavioural therapy; PTSD, post-traumatic stress disorder; RR, relative risk; SMD, standardized mean difference.

RR (of categorical data): RR = 1, same as control; RR < 1, intervention better; RR > 1, control better.

SMD (of continuous symptom score): SMD = 0, no difference between intervention and control; SMD < 0, intervention better; SMD > 0, control better.

*Statistically significant difference at the p < 0.05 level.

Table 3. Summary of findings for each comparison for two active interventions.

Comparison outcome	Follow-up point	Contributing studies	Studies (n)	Sample (n)	RR (95% CI)	SMD (95% CI)	Grade rating
Trauma-focused treatments + TAU for SUD vs present-focused treatments + TAU for SUD
PTSD severity	Post-treatment	Norman et al. (2019)	1	119		−0.49 (−0.86, −0.13)*	Very low
	3–5 months	Norman et al. (2019)	1	119		−0.30 (−0.66, 0.06)	Very low
	6–13 months	Norman et al. (2019)	1	119		−0.44 (−0.81, −0.08)*	Very low
PTSD diagnosis	Post-treatment	Norman et al. (2019)	1	119	0.83 (0.69, 1.01)		Very low
Alcohol use	Post-treatment	Norman et al. (2019)	1	119		0.13 (−0.23, 0.49)	Very low
	3–5 months	Norman et al. (2019)	1	119		−0.08 (−0.44, 0.28)	Very low
	6–13 months	Norman et al. (2019)	1	119		0.06 (−0.30, 0.42)	Very low
Dropout		Norman et al. (2019)	1	119	0.48 (0.32, 0.72)		Very low
Adverse events		Norman et al. (2019)	1	119	No participants were discharged from the study owing to SAEs		Very low
Creating Change + TAU for SUD vs present-focused treatments + TAU for SUD
PTSD severity	Post-treatment	Najavits et al. (2018)	1	52		−0.18 (−0.72, 0.37)	Very low
	3–5 months	Najavits et al. (2018)	1	52		0.23 (−0.32, 0.77)	Very low
Alcohol use	Post-treatment	Najavits et al. (2018)	1	52		0.25 (−0.29, 0.80)	Very low
	3–5 months	Najavits et al. (2018)	1	52		−0.39 (−0.94, 0.16)	Very low
Substance use	Post-treatment	Najavits et al. (2018)	1	52		−0.15 (−0.70, 0.39)	Very low
	3–5 months	Najavits et al. (2018)	1	52		0.18 (−0.37, 0.72)	Very low
Adverse events		Najavits et al. (2018)	1	52	No AEs related to either treatment		Very low
Brief cognitive restructuring training vs brief experiential acceptance training
PTSD severity	Post-treatment	Stappenbeck et al. (2015)	1	58		0.24 (−0.28, 0.76)	Very low
Alcohol use	Post-treatment	Stappenbeck et al. (2015)	1	58		−0.46 (−0.98, 0.06)	Very low
Dropout		Stappenbeck et al. (2015)	1	60	1.07 (0.96, 1.21)		Very low
Web-based CBT + peer support vs web-based CBT
PTSD severity	Post-treatment	Possemato et al. (2019)	1	8		0.09 (−1.34, 1.52)	Very low
	3–5 months	Possemato et al. (2019)	1	8		−0.61 (−2.11, 0.88)	Very low
Alcohol use	Post-treatment	Possemato et al. (2019)	1	10		0.35 (−0.93, 1.63)	Very low
	3–5 months	Possemato et al. (2019)	1	10		0.46 (−0.84, 1.75)	Very low
Incentivized trauma-focused treatment + TAU for SUD vs standards trauma-focused treatment + TAU for SUD
PTSD severity	Post-treatment	Schacht et al. (2017)	1	50		−0.42 (−0.99, 0.14)	Very low
	3–5 months	Schacht et al. (2017)	1	47		−0.54 (−1.13, 0.04)	Very low
Alcohol use	Post-treatment	Schacht et al. (2017)	1	52		−0.29 (−0.94, 0.36)	Very low
	3–5 months	Schacht et al. (2017)	1	33		−0.21 (−0.91, 0.48)	Very low
Dropout		Schacht et al. (2017)	1	58	10.71 (1.46, 78.39)*		Very low
Adverse events					Randomized participants had 10 SAEs: 9 hospitalizations and 1 death. None of the SAEs was determined to be related to study participation		Very low
Sequential trauma-focused treatment + TAU for SUD vs integrated trauma-focused treatment + TAU for SUD
PTSD severity	Post-treatment	Kehle-Forbes et al. (2019)	1	157		0.03 (−0.28, 0.35)	Very low
	3–5 months	Kehle-Forbes et al. (2019)	1	141		−0.18 (−0.51, 0.15)	Very low
Alcohol use	Post-treatment	Kehle-Forbes et al. (2019)	1	159		−0.28 (−0.59, 0.04)	Very low
	3–5 months	Kehle-Forbes et al. (2019)	1	145		−0.19 (−0.51, 0.14)	Very low
Dropout		Kehle-Forbes et al. (2019)	1	183	1.57 (0.99, 2.48)		Very low

AE, adverse event; CBT, cognitive behavioural therapy; CI, confidence interval; PTSD, post-traumatic stress disorder; RR, relative risk; SAE, serious adverse event; SMD, standardized mean difference; SUD, substance use disorder; TAU, treatment as usual.

RR (of categorical data): RR = 1, same as control; RR < 1, intervention better; RR > 1, control better.

SMD (of continuous symptom score): SMD = 0, no difference between intervention and control ; SMD < 0, intervention better; SMD > 0, control better.

*Statistically significant difference at the p < 0.05 level.

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Data availability statement

This paper does not include any primary data.