Do adjuvant interventions improve treatment outcome in adult patients with posttraumatic stress disorder receiving trauma-focused psychotherapy? A systematic review

Figures & data

Table 1. Evidence table for included studies.

Adjuvant treatment	Study	EG	CG	n EG	n CG	Treatment success: Post	Treatment success: Follow up
Behaviour-based interventions
Art therapy	(Campbell et al., 2016)	CPT + Art therapy	CPT	5	10	PCL-M: EG = CG BDI-II: EG = CG
Breathing Biofeedback	(Polak et al., 2015)	TFCBT + Breathing Biofeedback	TFCBT	4	4	IES-R: EG = CG
Family therapy	(Glynn et al., 1999)	DTE + Family therapy	DTE	17	12	CAPS: EG = CG M-PTSD: EG = CG IOE: EG = CG	CAPS EG = CG M-PTSD: EG = CG IOE: EG = CG
Exercise	(Powers et al., 2015)	PE + E	PE	- ^a	- ^a	PSS-I: EG > CG^c
Hypnotherapy	(Galovski et al., 2016)	CPT + Hypnotherapy	CPT + Sleep symptom monitoring	52	56	CAPS: EG = CG BDI-II: EG = CG	CAPS: EG = CG BDI-II: EG = CG
Cognitive enhancers
Cortisol	(Yehuda et al., 2015)	PE + HCN	PE + Placebo	12	12	CAPS: EG > CG^d PSS-SR: EG > CG^d	CAPS: EG > CG^d PSS-SR: EG > CG^d
D-cycloserine	(de Kleine et al., 2012)	PE + DCS	PE + Placebo	33^b	34^b	CAPS: EG = CG PSS-SR: EG = CG BDI-II: EG = CG	CAPS: EG = CG PSS-R: EG = CG BDI-II: EG = CG
D-cycloserine	(Difede et al., 2014)	VRE + DCS	VRE + Placebo	13	12	CAPS: EG = CG PCL: EG = CG BDI-II: EG = CG	CAPS: EG > CG PCL: EG > CG BDI-II: EG > CG
D-cycloserine	(Litz et al., 2012)	EBT + DCS	EBT + Placebo	13	13	CAPS: EG < CG PCL: EG < CG BDI-II: EG < CG	CAPS: EG = CG PCL: EG = CG BDI-II: EG = CG
D-cycloserine	(Rothbaum et al., 2014)	VRE + DCS	VRE + Placebo	53	53	CAPS: EG = CG PSS: EG = CG	CAPS: EG = CG PSS: EG = CG
Oxytocin	(Flanagan et al., 2018)	PE + OT	PE + Placebo	8	9	CAPS: EG = CG PCL: EG = CG BDI-II: EG = CG
Yohimbine	(Tuerk et al., 2018)	PE + Yohimbine	PE + Placebo	14	12	CAPS: EG = CG PCL: EG = CG BDI-II: EG = CG	CAPS: EG = CG PCL: EG = CG BDI-II: EG = CG
Methylene blue	(Zoellner et al., 2017)	IE + Methylene blue	IE + Placebo	15	16	PSS-I: EG = CG PSS-SR: EG = CG QIDS-SR: EG = CG	PSS-I: EG = CG PSS-SR: EG = CG QIDS-SR: EG = CG

Note. For each study treatment success of the experimental group (EG) and the control group (CG) are compared for both post-treatment and follow up-treatment success. Directions of significant differences in treatment success are indicated by “>“ “<“. Non-significant differences are indicated by “ = “. Higher treatment success indicates heightened symptom reduction. CPT = Cognitive processing therapy; TFCBT = Trauma-focused Cognitive Behavioral Therapy; PE = Prolonged Exposure; VRE = Virtual Reality Exposure; EBT = Exposure-based Therapy; DTE = Directed therapeutic exposure; IOE = Impact of Event Scale; IES-R = Impact of Event Scale Revised; CAPS = Clinician-Administered PTSD Scale; PSS = PTSD Symptom Scale; PSS-SR = PTSD Symptom Scale – Self-Report; PSS-I = PTSD Symptom Scale – Interview; PCL = Posttraumatic Check List; BDI-II = Beck Depression Inventory Revised; M-PTSD = Mississippi Scale for Combat-Related Posttraumatic Stress Disorder; HCN = Hydrocortisone; DCS = D-cycloserine; OT = Oxytocin; a = Persons per group not mentioned; b = Intent-to-Treat sample; c = no inference statistical analysis; d = Analysis included both post and follow-up data.

Figure 1. Adapted PRISMA flow diagram (Moher, Liberati, Tetzlaff, & Altman, 2009).

Figure 2. Risk of bias summary: review authors’ evaluations of each internal bias risk item for all studies.

Figure 3. Risk of bias graph: review authors’ evaluation of each internal bias risk item presented as percentages across all included studies.

Campbell, M., Decker, K. P., Kruk, K., & Deaver, S. P. (2016). Art therapy and cognitive processing therapy for combat-related PTSD: A randomized controlled trial. Art Therapy, 33(4), 169–177.

 Web of Science ®Google Scholar

Polak, A. R., Witteveen, A. B., Denys, D., & Olff, M. (2015). Breathing biofeedback as an adjunct to exposure in cognitive behavioral therapy hastens the reduction of PTSD symptoms: A pilot study. Applied Psychophysiology and Biofeedback, 40(1), 25–31.

 PubMed Web of Science ®Google Scholar

Glynn, S. M., Eth, S., Randolph, E. T., Foy, D. W., Urbaitis, M., Boxer, L., … Crothers, J. (1999). A test of behavioral family therapy to augment exposure for combat-related posttraumatic stress disorder. Journal of Consulting and Clinical Psychology, 67(2), 243–251.

 Web of Science ®Google Scholar

Powers, M. B., Medina, J. L., Burns, S., Kauffman, B. Y., Monfils, M., Asmundson, G. J. G., … Smits, J. A. J. (2015). Exercise augmentation of exposure therapy for PTSD: Rationale and pilot efficacy data. Cognitive Behaviour Therapy, 44(4), 314–327.

 PubMed Web of Science ®Google Scholar

Galovski, T. E., Harik, J. M., Blain, L. M., Elwood, L., Gloth, C., & Fletcher, T. D. (2016). Augmenting cognitive processing therapy to improve sleep impairment in PTSD: A randomized controlled trial. Journal of Consulting and Clinical Psychology, 84(2), 167.

 PubMed Web of Science ®Google Scholar

Yehuda, R., Bierer, L. M., Pratchett, L. C., Lehrner, A., Koch, E. C., Van Manen, J. A., … Hildebrandt, T. (2015). Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: Randomized trial showing improved treatment retention and outcome. Psychoneuroendocrinology, 51, 589–597.

 PubMed Web of Science ®Google Scholar

de Kleine, R. A., Hendriks, G.-J., Kusters, W. J., Broekman, T. G., & van Minnen, A. (2012). A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder. Biological Psychiatry, 71(11), 962–968.

 PubMed Web of Science ®Google Scholar

Difede, J., Cukor, J., Wyka, K., Olden, M., Hoffman, H., Lee, F. S., & Altemus, M. (2014). D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: A pilot randomized clinical trial. Neuropsychopharmacology, 39(5), 1052–1058.

 Web of Science ®Google Scholar

Litz, B. T., Salters-Pedneault, K., Steenkamp, M. M., Hermos, J. A., Bryant, R. A., Otto, M. W., & Hofmann, S. G. (2012). A randomized placebo-controlled trial of D-cycloserine and exposure therapy for posttraumatic stress disorder. Journal of Psychiatric Research, 46(9), 1184–1190.

 PubMed Web of Science ®Google Scholar

Rothbaum, B. O., Price, M., Jovanovic, T., Norrholm, S. D., Gerardi, M., Dunlop, B., … Ressler, K. J. (2014). A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans. The American Journal of Psychiatry, 171(6), 640–648.

 PubMed Web of Science ®Google Scholar

Flanagan, J. C., Sippel, L. M., Wahlquist, A., Moran-Santa Maria, M. M., & Back, S. E. (2018). Augmenting prolonged exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. Journal of Psychiatric Research, 98, 64–69.

 PubMed Web of Science ®Google Scholar

Tuerk, P. W., Wangelin, B. C., Powers, M. B., Smits, J. A., Acierno, R., Myers, U. S., ... Hamner, M. B. (2018). Augmenting treatment efficiency in exposure therapy for PTSD: A randomized double-blind placebo-controlled trial of yohimbine HCl. Cognitive Behaviour Therapy, 14(5), 1–21.

 Google Scholar

Zoellner, L. A., Telch, M., Foa, E. B., Farach, F. J., McLean, C. P., Gallop, R., … Gonzalez-Lima, F. (2017). Enhancing extinction learning in posttraumatic stress disorder with brief daily imaginal exposure and methylene blue: A randomized controlled trial. The Journal of Clinical Psychiatry, 78(7), E782–E789.

 Web of Science ®Google Scholar

Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Annals of Internal Medicine, 151(4), 264–269.

 PubMed Web of Science ®Google Scholar