The details of the study participants and procedures are given elsewhere [7
] and are briefly summarized below.
The patients were recruited at the Department of Psychiatry, Kochi Medical School, or its affiliated hospital, Doujin Hospital, between April 2004 and April 2006. The inclusion criteria for the patients were as follows:
1. Aged 18–85
2. Diagnosed as suffering from major depressive disorder according to the DSM-IV[10
3. Expected to be on continuation/maintenance antidepressant therapy for at least nine months after the patients had responded to acute phase antidepressant therapy and were in partial or full remission, i.e. they no longer fulfilled the diagnostic threshold for major depressive episode
4. Not having undergone electroconvulsive therapy or not having electroconvulsive therapy already planned for the index episode
5. 5. Living with the family for 3
months or longer before participating in this study and being expected to live with the family during the investigation period
6. Having at least one family member living with the patient who was available for family interviews.
The following patients were excluded:
1. Patients were screened with the Mini-Mental Status Examination [11
] when dementia was clinically suspected and those scoring 23 or below were excluded.
2. Patients suspected of having organic diseases were examined using head magnetic resonance imaging, and those diagnosed as such were excluded.
The member of each family who was 18
years or older and who had contact with the patient for the longest time was regarded as his/her primary family member.
Of the 103 patients who met the above eligibility criteria, 57 patients and their family member provided written informed consent to participate in this study after full disclosure of the purposes and procedures of the study. The major reason for non-consent was that the primary family members were unable to participate in the four psychoeducation sessions because of their work.
This study was approved by the Ethics Committee of Kochi Medical School, and written informed consent was given by all the patients and their families. The trial is registered with UMIN-CTR (UMIN000005555).
The fifty-seven patients who consented were randomly allocated to the intervention and control groups and were followed up for nine months. A random sequence was generated using a random number table and was kept by an independent clerk who allocated the consecutive patient sample to the intervention or control groups. No stratification was used.
Both the intervention and control groups received the standard outpatient treatment, which was performed by psychiatrists who were kept unaware of the treatment allocation of the patients. This treatment as usual (TAU) consisted of an evaluation of psychiatric symptoms, assessment and management of drug treatment, and supportive psychotherapy on a bi-weekly basis. All the patients were kept on maintenance antidepressants.
The primary family members in the intervention group took part in family psychoeducation sessions with multiple primary family members without the participation of the patients. Only one family member per patient was allowed. The session was performed once every 2
weeks, and 4 sessions were regarded as one course. The themes of the four sessions were “Epidemiology and causes,” “Symptoms,” “Treatment and course,” and “Coping of the family with the patient.”
Each session lasted 90–120
minutes. The first 30
minutes were devoted to providing information regarding depression and its treatment. A video tape and a textbook explaining depression and its treatment were prepared for this study and were used as teaching materials. The next 60–90
minutes were devoted to group discussion and problem solving for emotionally difficult situations experienced by participating families.
In order to maximally facilitate group discussion, the number of participating family members was limited to five, while from the staff side,
one leader and two co-leaders, usually consisting of two psychiatrists and one psychologist, attended each session. The whole program was supervised by SI, who had 30
years of experience in psychoeducation for people with severe mental illness. The sessions were videotaped, and the treatment team discussed their performance after the session was over.
Cost and clinical assessments
The economic analyses were undertaken from the perspective of the direct costs to the National Health Insurance (NHI). In Japan,
all medical expenditures are priced by the NHI, of which 70% are reimbursed by the NHI and 30% are paid by the patients out of their own pocket, except in special circumstances. We therefore asked the patients to collect all their NHI bills and summed them for the duration of the study. The sums included both the 70% reimbursed and the 30% paid out of the patients’ own pocket. Non-health service expenditures and indirect costs were not considered in the analyses. The costs in Japanese yen were all converted to US dollars at a rate of 100
yen/ 1 US dollar, which is the rough average exchange rate for the past several years at the time of writing of this manuscript (November 2011).
To evaluate the depressive state, we administered the Hamilton Rating Scale for Depression (HAM-D) [12
] and the Beck Depression Inventory (BDI) [13
] before intervention and after 9
months. The treating psychiatrist, who was blinded to the intervention status, administered the HAM-D. The BDI-II was filled in by the patient himself. When the treating psychiatrist who was blinded to the allocated intervention recognized the re-emergence of a major depressive episode according to the DSM-IV in the course of the bi-weekly visits constituting the treatment as usual, the patient was referred to an independent psychiatrist who also was kept blind to the intervention group and who administered the HAM-D and BDI. Relapse/recurrence was declared when the diagnostic threshold for a major depressive episode as specified in the DSM-IV was met according to the interview by this independent psychiatrist. The number of depression-free days up to the relapse/recurrence was taken as the unit of effectiveness.
The time to relapse/recurrence was compared between the two groups using a Cox proportional hazard analysis. The arithmetic means of the relapse-free days and the NHI costs were compared by way of the non-parametric bootstrap method because the data had highly skewed distributions [14
Cost-effectiveness was evaluated by relating the differential cost per patient receiving either the intervention or the control treatment to the differential effectiveness of each treatment in terms of relapse-free days. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the mean cost divided by the difference in the number of relapse-free days.
A cost-effectiveness acceptability curve (CEAC) was drawn to show the probability that an intervention is cost-effective compared with the alternative, given the observed data, for a range of maximum monetary values that a decision-maker might be willing to pay for a particular unit change in outcome. The CEAC is derived from the joint distribution of incremental costs and incremental effects, as estimated by non-parametric bootstrapping of the observed data [15
]. The range of maximum monetary values per relapse-free day is given on the x-axis. Given a specified value of this ‘acceptable’ cost-effectiveness ratio (a point on the x-axis), the CEAC shows the probability that the data are consistent with a true cost-effectiveness ratio falling below that value (read off the y-axis). This approach avoids the difficulties associated with the estimation of confidence intervals for the ICER.
In Japan, family psychoeducation is not yet covered by the NHI and therefore is not yet priced. In this RCT psychoeducation sessions were therefore administered as a research intervention without any cost to the NHI or the patients. In this cost-effectiveness analysis we estimated the most reasonable cost of family psychoeducation as follows and drew CEACs under this and two more cost scenarios whereby the price was estimated at 50% and 150% of the baseline scenario. Given that three therapists, whose average wage can range between US$30 to $50 per hour including social security costs, attended each 2-hour session for five patients, we calculated that the most reasonable estimate of one family psychoeducation session would be US$50 per patient. We also performed two sensitivity analyses in which a session would be priced at US$25 and $75 per patient.
All data were analyzed using SPSS 18.0. The bootstrap re-sampling was performed with STATA 11.0. Except where otherwise noted, the means of continuous variables are reported, followed by the SD in parentheses.