Measures
The following instruments were used as measures for inclusion, predictors and/or measures of treatment outcome (all measures were translated into Norwegian, Swedish, and Danish):
Schedule for affective disorders and schizophrenia for school-age children – present and lifetime version (K-SADS-PL): The K-SADS-PL is a semi-structured diagnostic interview that assesses a range of child psychopathology and demonstrates favourable psychometric properties [
19]. K-SADS-PL has shown a good inter-rater reliability of 98% and a 1 to 5 week test-retest kappa of 0.80 for any anxiety disorder diagnosis [
19]. Convergent and divergent validity have been documented in a Nordic sample of adolescents [
20], moreover, the K-SADS have been used in previous OCD treatment trials [
17,
21]. Symptoms can be classified as “not present”, “possible”, “in remissions” or “certain”. In this study OCD diagnoses and comorbidity where based on symptoms classified as “certain” only.
Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS): The CY-BOCS is a widely used, clinical-rated, semi-structured interview assessing the severity of OCD symptomatology [
22]. The CY-BOCS records symptom categories and evaluates the severity of obsessions and compulsions using10 items, across five dimensions (time occupied by symptoms, interference, distress, resistance, and degree of control over symptoms). The total severity score range from 0 to 40. The CY-BOCS total score in range of 10–18, are considered mild, 19–28 moderate and scores from 29 and above severe [
23]. CY-BOCS shows reasonable reliability and validity; with good to excellent inter-rater agreement [
24,
25]. A high internal consistency, 0.91, 0.68 and 0.84, for obsessions, compulsions and total score respectively, have been shown [
26].
Clinical Global Impressions-Severity (CGI-S): Is a clinical rating of symptom severity. Ratings range from 0 (no illness) to 6 (extremely severe). The CGI-S correlates strongly with the CY-BOCS total score in paediatric OCD patients, and is widely used and has been shown to be treatment sensitive [
25,
27,
28].
Clinical Global Impressions-Improvement (CGI–I): The CGI-I is used to assess overall clinical improvement based on symptoms observed and impairment reported using a seven point scale ranging from 0 (very much worse) to 6 (very much improved). The CGI-I scale was dichotomized so patients that received a rating of 5 (much improved) or 6 (very much improved) were collapsed in the analyses. The clinical-rated scale has been used successfully in patients with OCD [
27,
29].
Children’s Global Assessment Scale (CGAS): is a clinician’s rating on a numeric scale (1–100) of the patient’s overall level of functional strain [
30]. The scale has shown good test-retest reliability (r = .62 and r = .76 with psychiatrist and staff respectively). Good inter-rater reliability as well [
31]. Furthermore, it has demonstrated both discriminant and concurrent validity [
30].
Socioeconomic Status (SES): We used Hollingshead’s two-factor index of social position to classify the socioeconomic position of each family [
32]. This two-factor index combines ratings of parental occupation (1–9 scale) and parental education level (1–7 scale). Occupation is given a weight of 5 and education a weight of 3, this generates a summary score. The total scores were transformed into an ordinal scale that ranged between 1 and 5. SES was further dichotomized into two categories, high SES (scores 4–5) and low SES (scores 1–3).
The Child Obsessive-Compulsive Impact Scale (COIS-R): The COIS is a 33-item self-report questionnaire designed to assess the impact of OCD symptoms on the psychosocial functioning of children and adolescent in home, social and academic environment [
1]. Both parent and youth versions are available. The patient and parents each rate how much difficulty the child have doing different everyday activities as a result of OCD. Each item is scored on a 4-point Likert scale (0 = not at all, 1 = just a little, 2 = pretty much, and 3 = very much). Both the child and parent versions have shown moderate to high internal consistency, for children α = 0.78 and parents α = 0.92 [
1].
Child Behavior Checklist (CBCL): The CBCL is a 113-item parent-report form designed to assess a wide range of child behavioural and emotional problems. Parents rate items on a three-point scale (0 = not true; 1 = somewhat or sometimes true; and 2 = very or often true). This widely used index has established psychometric properties across a variety of clinical and non-clinical populations [
33]. The CBCL has shown a mean test-retest reliability between 0.95-1.00 and internal consistency from α = 0.78 to α = 0.97 [
33].
Family Accommodation Scale (FAS): The FAS is a 12 item clinician-rated instrument, designed to assess the family’s accommodation to the child’s OCD-symptoms during the previous month [
34]. The FAS includes items that measures the extent to which family members provide reassurance or objects needed for compulsions, decreased behavioural expectations of the child, modify family activities or routines, or help the child avoid objects, places or experiences that cause distress. The FAS has demonstrated good psychometric properties including good internal consistency (α = 0.76 to α = 0.80) [
34,
35], and positive correlation with measures of OCD-symptoms severity [
36] and family discord [
34].
Screen for Child Anxiety Related Emotional Disorders (SCARED): The SCARED is a psychometrically sound child- and parent-report questionnaire which assesses the presence of DSM-IV anxiety symptoms [
37,
38]. SCARED total scores were used in these analyses. Scores range from 0 to 82 with higher scores indicating greater impairment and severity. The internal consistency of the SCARED total score was α = 0.94 [
39].
The Mood and Feelings Questionnaire (MFQ): The MFQ is based on DSM-III-R criteria for depression and assesses the presence of depressive symptoms by means of 13 items [
40]. Scores range from 0 to 26 with higher scores indicating greater impairment and severity. The MFQ has sound psychometric properties [
41], and the MFQ total score has shown internal consistency of α = 0.75 to α = 0.78 [
42].
Family history of OCD: during baseline assessment parents were asked, in a clinical interview, if they ever have been suffering from OCD. For the present study, a positive family history of OCD means that either the parent(s) and/or the siblings of the identified patient had been diagnosed with OCD.
Parental psychopathology: During baseline assessment parents were asked about psychological symptoms and diagnosed psychiatric problems (yes/no). For the present study, a positive history of parental psychopathology means that a parent(s) of the identified patient had been diagnosed with any psychiatric diagnosis.
Autism Spectrum Screening Questionnaire (ASSQ): The ASSQ was used for a dimensional measure of autism spectrum symptoms [
43]. The internal consistency of the ASSQ total score was α = 0.86 [
43].
The EAS Temperament Questionnaire (EAS): was used for a dimensional measure of temperament. The questionnaire is a parent report consisting of 20 Likert-scaled items relating to three subscales: emotionality, activity and sociability. The internal consistency of the EAS total score has shown to be α = 0.70 [
44].
Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents (KINDL): was used as self-report questionnaire for children and adolescents as well as a proxy version completed by one of the parents to assess perceived quality of life [
45]. The questionnaire consists of 24 items equally distributed into seven subscales. Mean item scores are calculated for all subscales and the total quality of life (QOL) scale, which are transformed to a 0–100 scale, 0 indicates very low and 100 very high QOL. The internal consistency for the children’s self-report total score was α = 0.82 [
45].
Five Minute Speech sample (FMSS): The FMSS provides a measurement of parents’ Expressed Emotion (EE) toward their child [
46]. The criteria for scoring EE from the FMSS were developed by Magaña et al. (1986) and are based on analyses of the affective quality of the total five minute monologue. Inter-rater reliability is assessed regularly in the laboratory, internal consistency range from α = 0.70 to α = 0.80 [
47].
Compliance: During the treatment the clinician assessed the patients’ and the parents’ compliance to the therapy and in therapy. This assessment was done in sessions 2, 7, and 13. Compliance was assessed at a five point scale ranging from 0 (no compliance) to 4 (very good compliance).
Credibility: During treatment, in sessions 2, 7 and 13, the patients and the parents were given a form. They were asked to rate their credibility to the CBT-treatment, if they believed that the therapy would be helpful for them. Credibility was assessed at a five point scale ranging from 0 (no credibility to the therapy) to 4 (very much credibility).
Treatments
CBT step 1
CBT step 1 involved E/RP based on the treatment manuals by March and Mulle as well as an adapted version by Piacentini (unpublished material, 1998), adding more family intervention. The manual was translated from English and adapted to fit Nordic conditions by a group of therapists from the three Nordic countries [
48]. Only minor adaptations were necessary, mostly by revising the overall instructions and general descriptions of the main components of the treatment and by putting some more weight on the CBT triangle (the interrelation between thought-emotion-behaviour). Also, our manual put some more stress on the importance of the formulation of exact goals for the child’s play. Nevertheless, the main components from the manuals by March and Mulle, and by Piacentini, were kept unchanged.
An overview of the treatment sessions and the assessment procedures is presented in Table
1.
Table 1
Content of CBT-sessions and assessments
0 | Assessment by independent evaluator | K-SADS, CBCL, CY-BOCS, CGI, MFQ, ASSQ, COIS, CGAS, FAS, EAS, SCARED-R | Whole session |
1 | Psycho-education: Model for understanding and treatment | CGI-I, Compliance | Whole session |
2 | Externalising of OCD | CGI-I, | Whole session |
3 | Cognitive training and further assessment of OCD | CGI-I, | 30 min |
Parents: Negative attributions on OCD and the child |
4 | Test-exposure and tool box | CGI-I, | 30 min |
Parents: Parents’ role, guilt-feeling and self-reproach |
5 | E/RP; fight against OCD | CGI-I, | 30 min |
Parents: The family’s involvement in OCD |
6 | E/RP; get more control over OCD | CGI-I, | 30 min |
Parents: The child’s own responsibility for the treatment |
7 | E/RP; support the child or the OCD? | CGI-I, Compliance, CY-BOCS, CGAS, to bring home: MFQ, COIS | Whole session |
Joint hour with parents: Repetition of parents’ role, milestones |
8 | E/RP; comorbidity and special therapeutic needs. | CGI-I, | 30 min |
Parents: Secondary winnings and other obstacles |
9 | E/RP; continue the fight against OCD | CGI-I, | 30 min |
Parents: Separate OCD from other problems |
10 | E/RP; continue the fight against OCD | CGI-I, | 30 min |
Parents: Unity and taking care of the family |
11 | E/RP; Going through the treatment session | CGI-I, | Whole session |
Parents: Group-gathering – problem solving |
12 | E/RP; turning point | CGI-I, | 30 min |
Parents: How can parents prevent relapse |
13 | E/RP; prevent relapse | CGI-I, Compliance, CY-BOCS, CGAS. | 30 min |
Parents: What to do in case of relapse | CBCL, MFQ, COIS, SCARED-R. |
| Check that date for independent evaluation is set | | |
14 | Closing ceremony | CGI-I, | Whole session |
Getting together with the parents: Going through the treatment process |
All included patients should ideally have 14 sessions across 14 weeks. Breaks in CBT treatment were minimized and out of 14 sessions at least 10 were performed during at most 4½ months.
In doubtful cases the research group decided whether a patient was to be excluded due to fragmented CBT. Children who were early responders and who wanted to terminate treatment were encouraged to continue to 14 sessions, however, if not possible and fewer sessions had to be allowed (e.g. 1–7 sessions of CBT), ratings at 14 weeks post start should be fixed in time.
Patients who dropped out during step 1 or later were followed in an observational co-study of the NordLOTS using the same follow-up time points.
Step 2 CBT
For step 2, patients were randomized to either SSRI-treatment or CBT in a revised/reformulated version.
Patients randomized to continued CBT received 10 additional treatment sessions over 16 weeks. The same CBT-principles as used in step 1 were used in step 2. However, the therapist was allowed to take an individual approach to treatment based on reassessment of the patient, focusing on factors that may have led to inferior CBT-response. E/RP was adjusted to the problems encountered in step 1. Avoidance was also reassessed, and measures taken to minimize it. In this way the therapist was allowed to adapt CBT-manual to the individual child, situation, family expectations, etc. This was done in order to examine if a more individualized approach could make the CBT-treatment more effective.
Step 2: Medication
The treatment of sertraline included 6 sessions over 16 weeks (week 0, 2, 5, 8, 12, and 16). The pharmacotherapy treatment manual was adapted from the manual used in the POTS study [
49]. A starting dose of 25 mg was titrated up to 100 mg over four weeks. Children below 10 years with low weight could be given a lower starting dose. If response was inadequate at a stable dose of 100 mg, after a minimum of 3 weeks, the dose was increased after serum concentration was controlled, if deemed necessary, up to a maximum 200 mg. Response and side effects were controlled at every visit, and dose reduced if necessary. The manual consisted of CBT-support where patients were instructed to practice exposure tasks learned in step 1 outside the study sessions. The main aims of the CBT support was to maintain treatment gains from the first step, to support an active fight against OCD-symptoms upholding a belief that the medication will help, to increase compliance and identify obstacles, and to ensure that medication is accompanied by the same psychological attitude in all cases. However, no new tasks were introduced.
Parents were involved at all medication visits, receiving feed-back about the child’s progress and treatment. While parents were encouraged to praise the child for resisting compulsions, other interventions directed at parents were prohibited during pharmacotherapy (Table
2).
Table 2
Assessments and dosing schedule in sertraline step 2
| | | | Check Adverse Events Scale (baseline) (AE), Somatic assessment (SA), Clinical Global Impression (CGI) |
0 | 25 × 3 days, then 50 | 25-50 | CY-BOCS incl. CGI (use CY-BOCS at step 1 session 13 if < 3 weeks, else reassessment in point 10c above), CGAS, blood pressure (BP), pulse, weight, length, side effects (AE) | AE, SA, CGI, Clinical Global Impression - Improvement (CGI-I) |
2 | 75 | 50-75 | CGI-I, CGI, BP, pulse, weight, length, side effects, treatment credibility | AE, SA, CGI, CGI-I |
3-4 | 100 | 75-100 | CGI-I, CGI, BP, pulse, weight, length, side effects | AE, SA, CGI, CGI-I, dose correction based on response |
5-7 | 150 | 75-150 | CGI-I, CGI, BP, pulse, weight, length, side effects, treatment credibility, KINDL (“independent rater”) | AE, SA, CGI, CGI-I, dose correction on response |
8-12 | 200 | 75-200 | CGI-I, CGI, BP, pulse, weight, length, side effects, treatment credibility | AE, SA, CGI, CGI-I, dose correction based on response |
12-16 | 200 | 75-200 | CY-BOCS incl. CGI/CGI-I, CGAS, Scared-R, MFQ, COIS, FAS, KINDL (“independent rater”), BP, pulse, weight, length, side effects, treatment credibility | AE, SA, CGI, CGI-I, dose correction based on response |
Response to step 2 sertraline treatment
If assessments in session six (at 16 weeks) showed the patient to have a CY-BOCS score of 15 or below, the patient was considered a responder and went to follow-up including sertraline medical checkup and eventually sertraline treatment termination.
If assessment in session six at 16 weeks showed the patient to have a CY-BOCS score of 16 or above this patient was a non-responder and went to step 3 (see later).
Medical checkups and assessments took place every third month. As part of the follow-up (see later) assessments were performed after 6, 12, 24, and 36 months.
Maintenance doses of sertraline
Criteria for lower maintenance dose were checked at every visit: if the patient was very much improved (CGI-I = 6), if the OCD-illness was subclinical or in full remission (CGI-S = 0 or 1), if CY-BOCS scores are ≤ 10 points.
If lowered dose lead to worsened OCD or functioning, the dose was increased to full level again.
Criteria for sertraline termination
If a patient fulfilled termination criteria during medication follow-up, i.e. 6 months of subclinical OCD or full remission, sertraline was lowered with 25% every one to two weeks until a sertraline dose of 25 mg.
Step 3: Aripiprazole augmentation to sertraline in CBT + sertraline non-responders
Patients who were non-responders or partial responders within step 2 of the NordLOTS-study were asked to participate in step 3. Step 3 was based on augmenting sertraline treatment with the antipsychotic drug aripiprazole. Thus, all patients in step 3 were given both sertraline and aripiprazole.
Patients who respond to this regime (i.e. CY-BOCS ≤ 15 and CGI-S ≤ 2, and CGI-I ≥ 5) are followed for the total three year period.
Follow-up
All included patients are being followed-up at 6, 12, 24, and 36 months. They will be assessed with the instruments described in Table
3.
Table 3
Overview of measurements
History | Yes | | | | | | | | | |
| Yes | | | Possible | | | | | | |
| Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | Yes | | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | Yes | | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | | | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | | | | Yes | Yes | Yes | Yes |
| Yes | | Yes | | Yes | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | | Yes | Yes | Yes | Yes | Yes | Yes |
| Yes | | Yes | | Yes | Yes | Yes | Yes | Yes | Yes |
MFQ | Yes | | Yes | | | Yes | | | | |
SCARED | Yes | | Yes | | | Yes | | | | |