Acceptance and Commitment group Therapy for patients with multiple functional somatic syndromes: a three-armed trial comparing ACT in a brief and extended version with enhanced care.

BACKGROUND: Psychological treatment for functional somatic syndromes (FSS) has been found moderately effective. Information on how much treatment is needed to obtain improvement is sparse. We assessed the efficacy of a brief and extended version of group-based Acceptance and Commitment Therapy (ACT) v. enhanced care (EC) for patients with multiple FSS operationalised as Bodily Distress Syndrome multi-organ type. METHODS: In a randomised controlled three-armed trial, consecutively referred patients aged 20-50 with multiple FSS were randomly assigned to either (1) EC; (2) Brief ACT: EC plus 1-day workshop and one individual consultation; or (3) Extended ACT: EC plus nine 3-h group-based sessions. Primary outcome was patient-rated overall health improvement on the five-point clinical global improvement scale 14 months after randomisation. A proportional odds model was used for the analyses. RESULTS: A total of 180 patients were randomised; 60 to EC, 61 to Brief ACT, and 59 to Extended ACT. Improvement on the primary outcome after Extended ACT was significantly greater than after EC with an unadjusted OR of 2.9 [95% CI (1.4-6.2), p = 0.006]. No significant differences were found between Brief ACT and EC. Of the 18 secondary outcomes, the only significant difference found was for physical functioning in the comparison of Extended ACT with EC. CONCLUSIONS: Patients rated their overall health status as more improved after Extensive ACT than after EC; however, clinically relevant secondary outcome measures did not support this finding. Discrepancies between primary and secondary outcomes in this trial are discussed.

The use of prescription medication in 239 patients with multiple functional somatic syndromes.

OBJECTIVE: To describe the use of prescription drugs and their association with patient characteristics in patients with multiple functional somatic syndromes (FSS) focusing on drugs generally recommended and not recommended in FSS treatment. METHOD: Using data from a national prescription registry, we describe the drug use during a two-year period for 239 trial participants. Using regression models, we analyse the associations of patient characteristics with the patterns of use of antidepressants, anticonvulsants, opioids and sedatives. RESULTS: The use of prescription drugs was highly heterogeneous. Antidepressants were used at least temporarily by 34% (88/239), anticonvulsants by 7% (16/239), opioids by 26% (61/239) and sedatives by 20% (47/239) of the patients. Severe impairment due to multiple FSS was associated with use of opioids or sedatives (OR 6.49 (95% CI 2.68-15.68; p < 0.001)) but also with use of antidepressants or anticonvulsants (OR 3.42 (95% CI 1.35-8.65; p = 0.009)). Poor self-reported physical health, additional physical comorbidities and low socioeconomic status were associated with use of opioids or sedatives only. CONCLUSION: Antidepressants and anticonvulsants were modestly used. Opioids and sedatives were especially used by the severely affected patients. Balancing treatment expectations and enhancing patients' understanding of FSS may direct treatments towards more generally recommended drugs.

Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.

BACKGROUND: Functional somatic syndromes, including chronic fatigue syndrome or irritable bowel syndrome, often co-exist. Treatment guidelines supported by high quality evidence exist for most functional somatic syndromes, but are lacking for multiple comorbid functional somatic syndromes. We aimed to assess the effect of the tricyclic antidepressant, imipramine, in patients with multiple functional somatic syndromes defined by the criteria for multiorgan bodily distress syndrome, a unifying diagnosis that encompasses most functional somatic syndromes and somatoform disorders. METHODS: In this single-centre, double-blind, randomised trial done in a Danish university hospital setting, participants were patients consecutively referred (age 20-50 years) fulfilling criteria for multiorgan bodily distress syndrome with no concurrent comorbid depression or anxiety disorder. Participants were randomly assigned (1:1) to receive either 10 weeks of low-dose imipramine or placebo (oral daily doses of 25-75 mg). The hospital pharmacy handled randomisation (computer-generated) and masking, providing sequentially numbered packs of study drug that were given serially to the participants. All others involved were masked to allocation. Primary outcome was patient-rated overall health improvement on a 5-point clinical global improvement scale. Improvement was defined as patients responding "better" or "much better" as opposed to "unchanged" and "worse" or "much worse" when rating their overall health status after 10 weeks of minimum 25 mg study drug. Analyses included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01518634. FINDINGS: Between Jan 30, 2012, and Nov 24, 2014, 138 patients were randomly assigned; 70 to receive imipramine and 68 to receive placebo. The study was completed on May 1, 2015. 125 patients received at least one dose of study drug: 65 received imipramine and 60 received placebo. Treatment was terminated prematurely for eight (12%) patients receiving imipramine and seven (12%) patients receiving placebo. Data were missing for two (3%) patients receiving imipramine and three (5%) patients receiving placebo. Of the 120 patients (96%) who provided primary outcome data, 33 (53%) receiving imipramine reported their overall health status as "better" or "much better" compared with 14 patients (25%) receiving placebo. The improvement after imipramine was significantly greater than after placebo (odds ratio 3·3 [95% CI 1·6-6·8]; p=0·001). Number needed to treat was 3·6 (95% CI 2·3-8·9). Analysis of the worst-case scenario for patients with missing outcome did not change the interpretation of the results. 32 patients (49%) receiving imipramine and 10 patients (17%) receiving placebo had at least one adverse event of moderate intensity (p=0·0001); eight patients (12%) receiving imipramine and three patients (5%) receiving placebo had at least one adverse event of severe intensity (p=0·1496). One patient (1%) receiving placebo experienced a serious adverse event (a subdural haematoma sustained after an accident). Adverse events caused dropout in four patients (6%) receiving imipramine and three patients (5%) receiving placebo. INTERPRETATION: Imipramine treatment compared with placebo significantly improved overall health in patients with multiple functional somatic syndromes when both treatments were supported by regular contacts with clinicians. Adverse events were more common in the imipramine group, but only rarely led to discontinuation of treatment. FUNDING: The Danish Foundation, Trygfonden.