Quantity of evidence reflected the number of studies that were included as the evidence base for each ranking. The quantity assessment also took into account the number of participants in relation to the frequency of the outcomes measured (i.e. the statistical of the studies). Small underpowered studies that were otherwise sound may have been included in the evidence base if their findings were generally similar- but at least some of the studies cited as evidence must have been large enough to detect the size and direction of any effect. of evidence reflected the study design. Details of the study designs included in this REA were assessed against a hierarchy of evidence commonly used in Australia: Level I: A systematic review of randomised controlled trials (RCTs) Level II: A RCT Level III-1: A pseudo-RCT (i.e. a trial where a pseudo-random method of allocation is utilised, such as alternate allocation). Level III-2: A comparative study with concurrent controls. This can be any one of the following: Non-randomised experimental trial [this includes controlled before-and-after (pre-test/post-test) studies, as well as adjusted indirect comparisons (i.e. utilise A vs B and B vs C to determine A vs C with statistical adjustment for B)] Cohort study Case-control Interrupted time series with a control group Level III-3: A comparative study without concurrent controls. This can be any one of the following: Historical control study Two or more single arm [case series from two studies. This would include indirect comparisons utilise (i.e. A vs B and B vs C to determine A vs C where there is no statistical adjustment for B)] Interrupted time series without a parallel control group. Level IV: Case series with either post-test or pre-test/post-test outcomes Overall strength
A judgement was made about the strength of the evidence base, taking into account quality and risk of bias, quantity of evidence and level of evidence. Agreement was sought between three independent raters and consensus about the strength of the evidence base was obtained according to the following categories. High strength One or more level I studies with a low risk of bias OR three or more level II studies with a low risk of bias Moderate strength One or two level II studies with a low risk of bias OR two or more level III studies with a low risk of bias Low strength One or more level I to level IV study with a high risk of bias Direction The direction component of the ranking system a judgement as to whether the results are in a positive or negative direction. In cases where there are studies which show findings in different directions, preference is given to the direction of the study findings with the highest level and best quality. Positive direction The weight of the evidence indicates positive results Unclear direction The evidence does not show significant effects OR the results are mixed Negative direction The weight of the evidence indicates negative results Consistency The consistency component of the ranking system of the body of the evidence assesses whether the findings are consistent across the included studies (including across a range of study populations and study designs). It was important to determine whether study results are consistent to ensure that the results are likely to be replicable or only likely to occur under certain conditions. All studies are consistent reflecting that results are highly likely to be replicable Most studies are consistent and inconsistency may be explained, reflecting that results are moderately- highly likely to be replicable Some inconsistency reflecting that results are somewhat unlikely to be replicable All studies are inconsistent reflecting that results are highly unlikely to be replicable
Appendix 4 Evidence Profile Authors & year Design Sample % of sample with adjustment disorder (Diagnostic method), stressor Intervention type (Name) Key intervention components Intervention delivery method, frequency, duration, (delivered to) Outcomes (Measure(s)) Participants Behavioural-based Arends et al. (2014) Clustered RCT with 3, 6 and 12 month follow-up Dutch workers who returned to work after sickness absence due to mental health disorders Intervention: Age: 41.3 Male: 27% Control: Age: 43.3 Male: 38% Intervention: 73% Control: 50% (ICD-10) Stressor: Not reported Problem solving intervention (SHARP) Intervention: 1. Create inventory of problems related to return to work 2. Develop solutions and an action plan 3. Evaluate action plan/implemented solutions Control: Care as usual (Guidelines around management of mental health problems in workers) Occupational therapist delivered 30 minute consultations (2 – 5 sessions) over 3 months Hospital Anxiety and Depression Symptom Questionnaire Return to work N = 153
Both groups improved on mental health functioning at all follow-up time points, with no significant differences between groups in level of improvement. Full return to work occurred 65 days earlier and partial return to work occurred 12 days earlier for the intervention group compared to controls. Hosaka et al. (2000) Single group with 6 month follow-up Japanese cancer patients Age: 51.3 (8.8) Male: Unknown 26% (DSM-IV) Stressor: Not reported Psychiatric intervention Cancer psychoeducation Problem-solving Psychological support Relaxation training Guided imagery (cancer-focused) Five weekly 90 minute group based sessions - Profile of Mood States (POMS) N = 47 There were no significant changes in individuals with adjustment disorder from pre to post treatment or at follow-up. Hosaka et al. (2001) Single group with 6 month follow-up Japanese cancer patients Age: 50.2 (6.0) Male: Unknown 26% (DSM-IV) Stressor: Not reported Psychiatric intervention Cancer psychoeducation Problem-solving Psychological support Relaxation training Guided imagery (cancer-focused) Five weekly 90 minute group based sessions, followed by 3 further monthly free talk group session - Profile of Mood States (POMS) N = 34 post post
This study reported contradictory findings. Relaxation-based Bos et al. (2014) Pre-post psychiatric outpatients Age: 45.5 (10.5) Male 31% 10% adjustment disorder Stressor: Not reported Mindfulness training (MBSR + MBCT) Formal mindfulness exercises (Body scan, sitting meditation, yoga) Group discussion of above experiences Psychoeducation Homework Group therapy for 8 weekly session of 2.5 hours each - Short Symptom List (SSL) - World Health Organization Quality of Life N = 214 The adjustment disorder sub-analyses revealed a significant improvement to SSL and WHOQOL-Bref scores, with moderate to large effect sizes of d = 0.59 and 0.87, respectively. et al. (2014) RCT with 5, 8, and 14 month follow-up Taiwanese psychiatric outpatients Intervention: Age: 44.5 100% adjustment disorder with depression (DSM-IV) Holistic/Eastern therapy Intervention: Treatment as usual (TAU) + 1. Cognitive restructuring weekly sessions - Beck Depression Inventory (BDI) - Trait Anxiety Inventory (STAI) N = 71
Male 32% Control: Age: 44.0 Male 27% Stressor: Not reported 2. Meditation, relaxation and guided imagery 3. Emotion work 4. Physical exercises 5. Spiritual work Control: TAU (medication and psychoeducational advice) - Suicidal ideation Both groups showed significant reductions in the BDI and STAI, with no significant differences between groups. Suicidal ideation decreased significantly for both groups and there was a greater reduction in suicidal ideation in the intervention group. Cognitive behavioural therapy based Bachem & Maercker (2016) RCT with 3 follow-up (for only) Burglary victims Intervention: Age: 50.4 (15.7) Male 21% 100% adjustment disorder or adjustment disorder symptomatology (ICD-11) Self-help bibliotherapy Intervention: Manualised self-help including psychoeducation, learning coping strategies, activation Self-help manual self-administered over 1 month - Adjustment disorder New Module – 20 (ADNM-20) - Post-traumatic stress symptoms N = 103 trial
Lagerveld et al. (2012) Clustered controlled with 12 month follow-up Dutch employees on sick leave due to psychological problems 67% adjustment disorder Stressor: Not reported Psychological therapy Intervention: CBT, which was CBT with a work context, plus an additional module focusing on returning to work Control: Manualised CBT Intervention: Individual therapist delivered 12 sessions over 6 months Control: Individual therapist delivered 12 sessions over 6 months - Symptom Checklist - Depression anxiety and stress (DASS-21) N = 208 While the intervention was more effective on return to work levels, it did not significantly differ from controls in the impact on mental health outcomes. Depression and anxiety levels significantly improved in both groups but there was no significant impact of either intervention or control on stress levels. Powell & McCone (2004) Case study US military cadet Age: 20 Male 100% adjustment disorder with anxiety Stressor: Terrorism Psychological therapy CBT with the following components: Cognitive impulse control Challenging irrational beliefs Stress management skills Relaxation training 13 sessions over 12 months Outcome Questionnaire 45 (OQ-45) N = 1
The individual participant showed a reduction from 66 on the OQ-45 at the first session to at 12 month follow-up. van der Heiden & Melchior (2012) Pre post with three month follow-up Dutch GP patients referred to an outpatient treatment centre Age: 43.6 Male 32% 100% adjustment disorder: 50% with depressed mood; 30% with anxiety; 20% other (DSM-IV) Stressor: Not reported Psychological therapy Manualised CBT consisting of psychoeducation, self-monitoring of stress, improving lifestyle and coping strategies, modifying negative thoughts Individual weekly 45 minute sessions - Symptom Checklist N = 10 were significant reductions in symptomatology as measured by the SCL-90 between pre and post treatment (d = 1.25) and from pre-treatment to follow-up (d = 1.37). van der et al. (2003) Cluster RCT with 12 month follow-up Dutch employees from a private company who were on 2 weeks sick leave for an 100% adjustment disorder Stressor: Not reported Psychological therapy Intervention: Graded activity approach resembling stress inoculation training (a form of CBT) Four to five consultations over six weeks, 90 minutes in length, delivered by occupational therapists and a - Symptom Checklist - Symptom N = 192
Both groups improved significantly in SCL-90 scores from pre-treatment to 3 months with no significant differences between groups. The additional 9 months of therapy in the control group did not add any significant improvement to participants, and at post-treatment for the controls (12 months) compared to the same time point of 9 month follow-up for the intervention group, scores did not significantly differ. Hofer et al. (2010) Pre-post Outpatients with an acquired brain injury (ABI) Age: 51 (36 – 61) Male 55% 100% adjustment disorder: depressed mood (80%); anxiety (20%) (DSM-IV-TR) Stressor: Health Psychological therapy Resource activation Problem activation Clarification of meaning Problem mastery Unlimited psychotherapy sessions which lead to on average 23 sessions over 12 to 18 months - Beck Depression Inventory (BDI) N = At the end of treatment, none of the patients retained their adjustment disorder diagnoses. From pre to post therapy, BDI scores reduced significantly (d = 1.3). Kramer et al. (2010) Pre-post French university students Age: 24 (3.86) Male 18% 100% with adjustment disorder with depressed mood (DSM-IV) Psychological therapy Manualised psychodynamic psychotherapy Treatment lasting up to one year of weekly sessions - Symptom Checklist N = 32
Male: 33% Both treatments lasted 8 weeks Clinical Global Impression (CGI) Quality of life (EORTC QLQ-C30) Both groups reduced significantly in their MADRS, HADS, HAM-A scores, and CGI scores in addition to improving their quality of life scores from to end of treatment. Those who received slow-up titration paroxetine had significantly lower MADRS scores at mid-treatment (4 weeks) and significant lower HADS scores at mid treatment (4 weeks) and end of treatment (8 weeks). There was no significant differences between groups on HAM-A scores or quality of life total scores at the end of treatment. There was no significant differences in CGI improvement between groups. Participants in the intervention arm (slow-up titration paroxetine) reported less side effects than the controls. Hameed et al. (2005) cohort followed over 4 months Primary care patients with depressive disorders receiving Age: Unknown Male: 20% 34% adjustment disorder with depressed mood (DSM-IV) Stressor: Not reported Pharmacotherapy (24% of patients received concurrent psychotherapy) Naturalistic delivery of antidepressant medication as determined by the depression management team - Number of DSM-IV symptoms - Patient Health Questionnaire (PHQ-9) N = 96
Response was defined as when any follow-up symptom value was equal to 0. Patients who continued to have 0 symptoms throughout the follow-up period were defined as a sustained response. Overall response to treatment for adjustment disorder participants was 33-100% and sustained response over 4 months was achieved for 33-100% of patients. No specific SSRI was found to be more effective than any other. Özten et al. (2015) Case study Psychiatric patient Age: 34 years Female 100% adjustment disorder with mood Stressor: Interpersonal Pharmacotherapy Sertraline (SSRI) started and discontinued due to side effects; Fluoxetine (SSRI) started and maintained + Couples psychotherapy Sertraline (25 mg/day – 50 mg/day) for a week, then fluoxetine (20m/g day) for 7 weeks Hamilton Depression Rating Scale (HDRS) Hamilton Anxiety Rating Scale (HAS) Beck Depression Inventory (BDI) N = 1 Pre-treatment scores were 18 (HDRS); 12 (HAS); and 24 (BDI), after 2 months of treatment scores had dropped to 11, 6, and 9. Pharmacotherapy – Anxious symptoms Nguyen et al. (2006) RCT with 1 week follow-up French outpatients seeing GPs 100% adjustment disorder with Pharmacotherapy Intervention: Etifoxine Intervention: 150 mg/day for 28 days Hamilton Anxiety N = 191
Intervention: Age: 44.0 (13.4) Male: 38% Control: Age: 42.0 (13.1) Male: 30% anxiety Stressor: 41% family-related; 30% work related; 9% health; 20% other anxiolytic) Control: Lorazepam (benzodiazepine) Control: 2 mg/day for 28 days Rating Scale (HAM-A) Clinical Global Impression Scale (CGI) Sheehan Disability Scale (SDS) Social Adjustment Scale Etifoxine was found non-inferior (i.e. at least as effective) to the control, but a significantly higher percentage of the treatment group were classified as responders (72%) at the end of treatment compared to controls (56%). Both groups improved in CGI ratings, but etifoxine had a higher proportion of markedly improved individuals. SAS-SR and SDS scores improved comparably between groups with no significant differences. Stein (2015) RCT South African outpatients Intervention: 100% adjustment disorder with anxiety Pharmacotherapy Intervention: Etifoxine anxiolytic) Intervention: Three capsules per day for 28 days (150mg/day) Control: Three Hamilton Anxiety Rating Scale (HAM-A) N = 201
Age: 40.0 (11.8) Male: 32% Control: Age: 38.9 (12.8) Male: 30% Stressor: 39% interpersonal, (38%) work/school; economic (12%); other (11%) Control: Alprazolam (benzodiazepine) capsules per day for 28 days (1.5mg/day) Self-report for the Assessment of Adjustment Disorders Alprazolam improved outcomes on HAM-A significantly more than etifoxine at day 7 but at day 35 (one week discontinuation), etifoxine demonstrated non-inferiority compared with alprazolam on HAM-A measures. There were no significant differences at day 35 for other measures. There were more adverse events reported in the alprazolam group. Combined psychological and pharmacotherapy Ichitovkina et al. (2014) Controlled cohort Russian combatants recently returned from assignment Intervention: Age: 40.0 (1.4) 60% with adjustment disorder: 27% with depressed mood; 32% with anxiety and depressed mood; 10% rehabilitation Psychological: Art therapy, collective hypnosuggestion, rational therapy, family therapy Pharmacotherapy: Primarily SSRIs and benzodiazepines Psychiatrist delivered 14 days of inpatient treatment followed by twice-weekly outpatient treatment for five weeks, consisting of - Adaptivity multi-factorial personality questionnaire (MPQ) N = 199