Six-year outcome in subjects diagnosed with attention-deficit/hyperactivity disorder as adults

In 2002, a special out-patient clinic for referral of adult subjects with suspected diagnoses of ADHD, autism spectrum disorders and Tourette syndrome was opened at Uppsala University Hospital. It was powered with a multidisciplinary team with senior psychiatrists, clinical psychologists, social workers and occupational therapists. The work was built on a stable structural diagnostic routine to enable follow-up for quality assurance and research purposes. Out of 233 subjects who were consecutively referred to a team led by senior psychiatrist D.E. between April 2002 and October 2010, 168 (78 women and 90 men) fulfilled diagnostic criteria of adult ADHD and were included in this study. See also Fig. 1.

The current follow-up was conducted between March and August 2013. Written informed consent was obtained from all included subjects. A questionnaire was distributed and later supplemented by an interview performed by a research nurse with extensive experience of handling subjects with ADHD. The study was approved by the Uppsala Regional Ethics and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

All included subjects were originally evaluated by a multidisciplinary team and diagnosed by the senior psychiatrist. The diagnostic procedure aimed at establishing best estimate diagnoses [25]. As reported in detail previously [9] ADHD symptomatology was assessed by a semi-structured interview based on the 18 DSM-IV criteria [26] and very similar to the SNAP-IV-18 [27]. In brief, answers were graded from 0 to 3 corresponding to symptom frequency and impairment: ‘never’, ‘sometimes’, ‘often’ and ‘very often’. An answer of ‘often’ or ‘very often’ was considered to represent a fulfilled DSM-IV criterion. The sum was presented as an ADHD-score, with a maximum value of 54. For the majority of subjects, childhood ADHD symptomatology could be confirmed by parents, other relatives, or childhood patient records. In 5 of the 124 included subjects diagnosis was based on self-reported childhood symptoms only, and two had diagnoses equivalent to ADHD in their childhood clinical records.

Current psychiatric comorbidity was evaluated by the Structured Clinical Interview for DSM-IV axis I disorders (SCID I) [28]. Criteria for DSM-IV axis II disorders were initially assessed by means of the DSM-IV and ICD-10 personality interview (DIP-I) [29], and after 2006 by the structured clinical interview for DSM-IV axis II (SCID-II) [30], which is very similar to the DIP-I, and was utilized for half of the included subjects. Figures for axis II disorders are reported based on the specific criteria only. The diagnostic interview for social and communication disorders [31], and the autism diagnostic interview-revised [32] were conducted by senior clinical psychologists for evaluations of suspected autism spectrum disorders.

All subjects were subject to physical examination including basic neurologic status, as well as routine laboratory testing including screening for illegal drugs.

The treatment protocol was individualised for each patient and based on a multimodal approach containing both pharmacological and a non-pharmacological measures.

Current symptoms and treatment history were assessed on average of 77 months after baseline and performed in two steps.

First, questionnaires were sent to the included subjects with questions about current symptoms of ADHD using a self-report version of the semi-structured interview utilized at baseline. Current functioning was assessed by a self-report version of the global assessment of functioning scale (GAF) [33]. Potential improvement since baseline was measured by a self-report version of the clinical global improvement scale (CGI-I), scoring 1–7, corresponding to answers “very much improved” to “very much worse” [34]. Disability and impairment were investigated by the Sheehan disability scale (SDS) [35] covering three domains: work/school, social life and family life/home responsibilities. SDS has recently been psychometrically evaluated in adult ADHD [36]. Health-related quality of life (HRQoL) was measured by EQ-5D and EQ-VAS [37]. Alcohol and drug consumption was assessed by the alcohol use disorders identification test (AUDIT) [38] and drug use disorders identification test (DUDIT) [39]. Twenty-nine participants were given support to fill in the questionnaires, 16 obtained telephone support and 13 were supported in their homes or during a visit to the clinic.

Second, after return of the questionnaires there was a telephone interview covering demographics as well as details of their past and current medical condition. The interview mainly functioned to validate that the patients have understood the questionnaires, and to give practical support to fill in the questionnaires. Twenty-nine participants were given such support.

Subjects’ own information regarding previous medication periods was validated against data in their patient files if available. In case of contradictory data, we choose to rely on patient file data. Slightly less than half of the subjects, 57 subjects; 46%, were on current medication, while 67 subjects were not. Mono-therapy was reported by all but three participants; methylphenidate in 46 subjects and amphetamine in eight subjects. Three subjects (5%) were treated with methylphenidate and atomoxetine in combination. A vast majority (84%) reported adherence to treatment on a daily basis. Fifty-five of those medicated had discontinued their medication and 12 (10%) were never treated. The 55 who had discontinued medication had been free of drugs for 41 ± 27 months; range 1–108, and 49 out of those had been free of drugs for a year or more at follow-up. In only two subjects the reason for discontinuation was the person’s own perceived clinical improvement.

Non-pharmacological measures included psychoeducation (received by 41%), social and similar support (34%), vocational support (44%) and psychological therapy (55%), either in a group or individualised. Any non-pharmacological intervention was given to 80% of the subjects.

The primary outcome measure was “remission”, which was defined as not fulfilling any ADHD subtype and a GAF-value of ≥ 70 during the last year.

Dichotomous data were analysed using Chi-square test statistics or Fisher’s exact test when applicable. Kolmogorov–Smirnov’s test was used to test for normality. When appropriate Mann–Whitney U test was used for analysis of group differences; otherwise the t test was performed for continuous data.

The strategy was to assess potential predictors of remission in stepwise binary logistic regression analyses, where variables which were significant in simple regressions should be included in a final model. Values are given as mean ± SD, or median with range within brackets. All statistical analyses were performed using IBM SPSS Statistics, version 23.

At follow-up, there was a decrease in mean ADHD score from 36.8 ± 7.8 to 25.5 ± 11.1 and 33% of the subjects, 41 out of 123, were in remission (Table 1). There was also a decrease in the number of subjects who fulfilled each of the 18 different DSM-IV ADHD criteria, and which was similar for each of the criteria (Fig. 2). It was also noted that there was an apparent change in ADHD subtype over the observation period.

Those in remission reported similar ADHD scores at baseline as those who were not in remission. Furthermore, there was no difference in current medication between those groups; 51% vs. 43% (Table 2). Reciprocally, there was no difference in remission rate between subjects in the current medication group, 37%, and in those not currently medicated, 30% (Table 3). Those medicated reported similar ADHD scores as those without ongoing medication both at baseline and at follow-up. The change in ADHD score between the two time periods was also very similar. Finally, there were no significant differences between the current-treatment group and those not medicated with respect to age, sex, or axis I or axis II comorbidity at baseline (data not shown).

All baseline variables recorded in Table 1, plus treatment-related variables, were tested for possible inclusion in a regression model with remission as the dependent variable. None of these variables was, however, significantly related to remission.

First, this study did not evaluate on-going psychiatric comorbidity at follow-up. There was, however, no difference in the number of comorbidities at baseline between those that remitted and those that did not, or in those that continued and those who discontinued their medication. Furthermore, in a prior study those in remission did not have more remission from comorbidities at follow-up than those being non-remitters [12]. Second, ADHD baseline data were obtained by an interview and follow-up in self-report form, although using the same questionnaire. This modality was chose of practical reasons and knowing that there was evidence that self-assessment of ADHD symptoms present with an acceptable validity and reliability; see, e.g., references [53, 54]. Likewise, a subject recall-bias over, e.g., adherence to treatment may be an issue over a period as long as 6 years [55]. On the other hand has been documented that adults can provide a reliable rating both of their own childhood and current symptoms in ADHD [56]. Third, differences in non-pharmacological treatment and/or supporting interventions since baseline are potential factors that could have biased the results. There were, however, no difference in the number of such interventions between those who continued and those who discontinued their medication and between those who were on remission and those who were not (data not shown). This observation must, however, be interpreted with caution due to the very low statistical power. Fourth, this cohort study was commenced at a time when initiation of treatment with stimulants was highly centralised to specialized centres, and when the awareness about the condition “adult ADHD” was low. This reasonably led to a selection bias. Consequently, results can a priori not be said to contradict those that are obtained in studies based on different modes of patient recruitment or follow-up times [24], or with a considerably higher attrition [40]. Fifth, this is a naturalistic study, and it is not random whether subjects ended up in the medicated or in the not-mediated group at follow-up. A faulty conclusion would be to avoid considering medication again in non-remitted subjects who have previously discontinued their pharmacological treatment. Finally, there is currently lack on sound information on whether any of the many scales used to assess ADHD is better than any other scales [57]. The scale scoring system used by us was constructed at a time when there was no widespread and internationally accepted scoring method based on all 18 DSM-IV criteria. It is very similar to the widely used adult ADHD self-report scale ASRS-1 which was published in 2005 [58], as is also the SNAP-IV-18 which, however, is phrased for children [27]. Consequently, there is no reason to suppose that the use of another similar scale would have generated different results.

This paper presents one of the longest naturalistic outcome studies of clinical subjects diagnosed with ADHD in adulthood. It is characterized by a very low attrition rate and almost three-fourth of the cohort was assessed after a mean of 6 years, which is substantially more than in previous prospective studies which present with dropout rates as high as 50–66% [24, 40]. All subjects were included consecutively after being diagnosed with ADHD and assessed by one senior psychiatrist. As subjects were first diagnosed and exclusively treated as adults there are no potential persisting effects of previous treatment in childhood.