The impact of insomnia disorder on adult attention-deficit/hyperactivity disorder severity: A six-month follow-up study

Highlights

Insomnia disorder remission is associated with a significant ADHD severity improvement.

Psychiatric ADHD comorbidity contributes to greater insomnia disorder persistence.

ADHD severity, rather than ADHD presentations, would be related to insomnia disorder persistence.

Insomnia disorder treatment would contribute to improve mental and physical adult ADHD HRQoL.

Abstract

Background and objectives

The longitudinal relationship between insomnia disorder and adult attention-deficit/hyperactivity disorder (ADHD) has been scarcely investigated. This study aimed to evaluate the relationship between the remission of insomnia disorder and adult ADHD clinical severity, psychiatric and medical comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up.

Methods

Ninety-two adult patients with ADHD and insomnia disorder (52.2% males; mean age 39.5 ± 11.0 years) were comprehensively assessed at baseline, 3 months, and 6 months of a follow-up period. The evaluation included semi-structured interviews (for ADHD and comorbidity assessment), the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of ADHD and insomnia disorder was performed according to DSM-5 criteria. At baseline and follow-up, psychoeducation/sleep hygiene and, if necessary, pharmacological were prescribed for insomnia.

Results

Eighty-seven patients completed the 6-month follow-up. Insomnia disorder remission was reported in 72.4% of cases and was related to a greater improvement in ADHD symptoms and severity throughout the follow-up period. Additionally, an improvement in psychiatric comorbidities and better HRQoL were associated with insomnia disorder remission.

Conclusion

The current study highlights that the treatment of insomnia disorder in ADHD adult patients may have an important role in the outcome of ADHD therapeutic approaches by reducing their severity.

Keywords

Insomnia disorder

ADHD

Severity

Comorbidity

Treatment

Psychiatric comorbidities

1. Introduction

Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder characterized by inattention and/or hyperactivity-impulsivity (APA, 2013). ADHD affects approximately 5% of children and adolescents, and 2–3% of adults worldwide (Faraone et al., 2015). Throughout an individual's lifetime, ADHD can increase the risk of other psychiatric disorders such as anxiety disorders, mood disorders, substance use disorders, behavior disorders, and sleep disorders (Faraone et al., 2015; Fayyad et al., 2017).

Insomnia is considered a highly distressing and disabling condition that is highly prevalent in the general population. The prevalence of insomnia symptoms ranges between 10 and 48% (Chung et al., 2015) while the prevalence of insomnia disorder is estimated at between 12 and 20% in the adult general population (Buysse, 2013; Morin et al., 2011; Roth et al., 2011). Insomnia usually has a chronic course in 40–70% of subjects suffering this condition (Buysse, 2013; Morin et al., 2009), and the prevalence of chronic insomnia is estimated at between 9 and 12% (Kay-Stacey and Attarian, 2016). Furthermore, insomnia has several negative consequences for individual functioning, and several studies have shown that it is related to impairments in productivity, absenteeism problems, and increased healthcare costs (Kessler et al., 2011).

Sleep problems are common and clinically severe among adults with ADHD, (Bjorvatn et al., 2017). It is reported that about 67% of adults with ADHD have insomnia symptoms compared to 29% in the general population (Brevik et al., 2017). This relationship has bidirectional consequences on both disorders, since greater severity of ADHD is associated with an increased risk of insomnia (Instanes et al., 2018; Schredl et al., 2007), and in the opposite direction, increased severity of insomnia worsens ADHD symptoms (Gamble et al., 2013; Gau et al., 2007; Mahajan et al., 2010). Likewise, some research suggests that insomnia is related to attentional impairments, leading to the intensification of ADHD-like symptoms (Voinescu et al., 2012; Wynchank et al., 2017). Besides, there is emerging evidence that insomnia also has a bidirectional relationship with other psychiatric disorders. Specifically, it may be a risk factor for depression and anxiety disorder (Blank et al., 2015; Okajima et al., 2012; Sivertsen et al., 2014), and depression and substance use disorders have been related to an increased risk of insomnia (Schredl et al., 2007; Sivertsen et al., 2015).

Recent studies suggest that pharmacological treatments for ADHD may have a beneficial effect on insomnia symptoms by improving daytime sleepiness (Boonstra et al., 2007; Surman et al., 2009; Surman and Roth, 2011; Tsai et al., 2019), especially ADHD stimulant medications (Brevik et al., 2017). Meanwhile, previous research reported that insomnia symptoms can be induced as an adverse effect of ADHD medications (both stimulants and atomoxetine) (Adler et al., 2009; Kirov and Brand, 2014; Kooij and Bijlenga, 2013; Wilens et al., 2002), this adverse effect seeming to be mitigated after two months (Lecendreux and Cortese, 2007; Stein et al., 2012).

Hence, adult ADHD and insomnia have a complex and not always well-understood relationship, as most studies have been conducted on child and adolescent populations. Despite the increased scientific interest in the relationship between ADHD and insomnia (some reviews and meta-analysis have been published on this issue), most research has been cross-sectional (Díaz-Román et al., 2018; Hvolby, 2015; Instanes et al., 2018; Schredl et al., 2007; Surman et al., 2009; Weibel et al., 2017; Yoon et al., 2013).

Few longitudinal studies have been published on adult ADHD and insomnia, and these have reported mixed conclusions. For instance, a four-decade longitudinal study showed that ADHD diagnosis in childhood is not related to insomnia symptoms at 38 years of age (Goldman-Mellor et al., 2014). Another longitudinal study on twins described how childhood ADHD were associated to poor quality sleep in young adulthood only if ADHD persists, and interestingly, ADHD and sleep disturbances in young adults were associated due to genetic and non-shared environmental influences (Gregory et al., 2017).

As stated above, the longitudinal relationship between insomnia disorder and adult ADHD has rarely been investigated. This study aims to evaluate the relationship between the remission of insomnia disorder and adult ADHD severity, psychiatric comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up. We hypothesize that insomnia disorder remission is associated to a greater clinical improvement in ADHD severity, and has a positive impact on psychiatric comorbidities and the HRQoL in adult ADHD patients.

2. Material and methods

2.1. Participants

This is a 6-month follow-up study conducted in the Adult ADHD Program of the Hospital Universitari Vall d'Hebron (Spain). 92 adult ADHD patients were recruited consecutively between April 2019 and June 2020. This study was approved by the hospital's Clinical Research Ethics Committee. All the participants voluntarily agreed to take part in the study and did not receive any financial compensation.

The inclusion criteria were to be over 18 years old, fulfill criteria for ADHD and insomnia disorder according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (APA, 2013), have stable ADHD pharmacological treatment without changes at least in the last 3 months, and accept and sign the informed consent prior to participation. Those patients with a sleep disorder diagnosis other than insomnia disorder (e. g., circadian rhythm disorder), intellectual disability (intelligence quotient below 70), or any medical condition that might explain ADHD-like symptoms were excluded.

2.2. Assessment

The adult ADHD and insomnia disorder diagnosis was established according to DSM-5 criteria by senior psychiatrists and psychologists experienced in the diagnosis of adult ADHD and sleep disorders. These trained practitioners also performed the entire assessment process using validated instruments.

2.2.1. ADHD assessment

The Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID) (Epstein and Kollins, 2006; Ramos-Quiroga et al., 2012) and the Diagnostic Interview for ADHD in Adults (DIVA 2.0) (Ramos-Quiroga et al., 2019) were used for ADHD diagnosis. The CAADID is a semi-structured diagnostic interview that evaluates ADHD from childhood to adulthood and the DIVA 2.0 assesses diagnosis criteria. The Conners’ Adult ADHD Rating Scales – Long Version(CAARS) (Macey, 2003) was used for clinical evaluation of ADHD. The clinical severity of ADHD was evaluated using the ADHD Rating Scale (ADHD-RS) (DuPaul et al., 1998), the Clinical Global Impression- Severity Scale (CGI-S) (Guy, 1976) and the Improvement scale (CGI-I) (Guy, 1976).

2.2.2. Insomnia disorder assessment

Three validated instruments were used to evaluate insomnia, sleep, and related disorders at baseline and at 3- and 6-month follow-up. Sleep quality and its alterations in the last month were assessed using the Pittsburgh Sleep Quality Index (PSQI) (Buysse et al., 1989) a 19-item self-reported questionnaire that assesses seven components related to sleep: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. The Insomnia Severity Index (ISI) (Bastien et al., 2001) was used to evaluate insomnia severity in the last month considering the severity of sleep onset, sleep maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. The Epworth Sleepiness Scale (ESS) is a self-reported eight-item scale (Johns, 1991) that was used to measure daytime sleepiness in the last month. Additionally, insomnia improvement throughout the follow-up was evaluated by the CGI-I (Guy, 1976). Patients’ previous diagnosis or current symptoms suggesting a sleep disorder other than insomnia (e.g., obstructive sleep apnea syndrome or circadian rhythm disorder) were clinically evaluated at baseline and at 3- and 6-month follow-up.

2.2.3. Psychiatry comorbidity assessment

The Structured Clinical Interview for DSM for axis I and axis-II diagnoses (SCID-I and SCID-II) (First, 1997) were used to assess patients’ psychiatric comorbidities other than ADHD and insomnia disorder. Moreover, the Beck Depression Inventory II (BDI-II) was used for the evaluation of depressive symptomatology (Beck et al., 1996). Finally, the State-Trait Anxiety Inventory (STAI) was administered to measure trait and state anxiety (Spielberg et al., 1970).

2.2.4. Health-Related quality of life (HRQoL) assessment

The short-form questionnaire SF-36 was used for HRQoL evaluation (Ware and Sherbourne, 1992). This questionnaire assesses eight domains that can be aggregated into two summary measures: physical component summary (PCS) and mental component summary (MCS).

2.3. Procedure

The Adult ADHD Program at the Hospital Universitari Vall d'Hebron is a comprehensive multidisciplinary program that evaluates and treats patients referred from primary care centers, community mental health centers, and addiction treatment units. Once referred to the ADHD Program, a complete assessment of the patient is carried out to establish the diagnosis and treatment.

For the current study, the assessment process consisted of five visits (three for the baseline evaluation and two for the follow-up evaluations) conducted by highly trained practitioners specialized in ADHD and sleep disorders (i.e. psychiatrists and psychologists). On the first visit, a complete medical history was obtained by the psychiatrist, including a clinical approach to ADHD and insomnia disorder. In addition, a standardized evaluation with validated instruments for ADHD (i.e. CAADID-I, DIVA 2.0, CGI-S) and insomnia (i.e. ISI, ESS, and PSQI) was conducted during the first visit. On the second visit, the psychologist completed the assessment with the remaining measures (i.e. CAARS, ADHD-RS, STAI, BDI, SF-36, SCID-I, and SCID-II). Finally, on the third visit, the psychiatrist reviewed all of the information and confirmed the ADHD and insomnia disorder diagnosis according to DSM-5 criteria.

The patients were followed up at 3 and 6 months to be evaluated again by the same psychiatrist using the assessment protocol (ADHD-RS, ADHD CGI-S, ADHD CGI-I, STAI, BDI, SF-36, PSQI, ISI, ESS, and insomnia disorder CGI-I). During the baseline and follow-up visits the psychiatrist provided the patient with psychoeducation/sleep hygiene, and if necessary, pharmacological treatment for insomnia was prescribed de novo, maintained, or removed – if insomnia disorder improved - according to clinical practice guidelines (Riemann et al., 2017). The self-reported use of electronic device screens in the half hour before bedtime was also recorded. In addition, in the follow-up visits, the patients’ sleep hygiene and hypnotic treatment adherence was recorded. Note that pharmacological treatment for ADHD was not modified during the follow-up period.

2.4. Analyses

Descriptive, bivariate, and multivariate analyses were conducted using SPSS (Version 20 for Windows). First, a descriptive analysis of all variables was performed in terms of percentages, means, and standard deviations. To compare patients with and without insomnia disorder, the Chi-square test and Student's t-test were carried out for qualitative and quantitative variables, respectively. Afterward, Bonferroni correction was used to counteract the Type 1 error. Only variables that retained statistical significance after the Bonferroni procedure were included in the logistic regression analysis. To avoid collinearity, variables related to sleep were not included in the multivariate analyses. A conditional entrance method was used to select variables in the model. The dependent variable was insomnia disorder status in the 3 and 6 months of follow-up (0 = no insomnia disorder and 1 = insomnia disorder). All statistical hypotheses were two-sided and a value of p <0.05 was considered statistically significant.

3. Results

3.1. Sample features at baseline and follow-up

During the recruitment period, 92 ADHD patients fulfilled the inclusion criteria and agreed to participate in the study (52.2% males; mean age 39.5 ± 11.0 years). Regarding ADHD presentations, combined presentation was the most frequent (64.1%), followed by inattentive (31.5%) and hyperactive/impulsive (4.3%) presentation. Regarding ADHD pharmacological treatment, metylphenidate and lisdexanfetamine were the most prescribed ADHD drugs (58.4% and 33.7%), whereas atomoxetine was reported in 7.6%. Psychiatric comorbidities were present in 70% of the sample, depressive and anxiety disorders being the most common (46.7% and 27.2% respectively). Sleep onset insomnia was reported in 73.9% of cases and 88% used screen devices in the half hour before bedtime. PSQI reported poor sleep quality in 96.7% of cases and as expected higher ISI and EW scores were reported. Finally, 32.6% received hypnotic treatment at baseline assessment, benzodiazepines (19.6%), antidepressants (7.6%) and melatonin (6.5%) being the most prescribed drugs.

All patients completed the follow-up at 3 months while 5 patients withdrew at 6 months (Fig. 1). Insomnia disorder remitted in 44.6% of cases at 3 months and in 72.4% at 6 months (Tables 1, 2, 3). None of the patients in whom the insomnia disorder remitted at 3 months had insomnia disorder at 6 months.

3.2. Results in relation to insomnia disorder remission

Sociodemographic, clinical, and psychometric variables are presented in Table 1. Regarding sociodemographic differences at 3 months, insomnia disorder was more frequently displayed in women (62.7%) and older patients (43.1 ± 9.3). However, no sociodemographic differences were found at 6-month follow-up. In the bivariate analysis, psychiatric comorbidities were associated with greater insomnia disorder persistence across both 3- and 6-month follow-up (91.7% vs. 25.4% at 6 months), especially mood disorders (58.3% vs. 15.9% at 6 months). Also, higher BDI and STAI scores were related to greater persistence of insomnia disorder, as well as the mental and physical component of SF-36 (Table 1).

No differences were found regarding somatic diseases or family psychiatric history. In addition, co-occurrent substance use disorder or personality disorder were not related to a higher persistence of insomnia disorder.

Table 2 shows the analyses by ADHD variables; a statistically significant improvement for ADHD severity (CGI-S, CGI-I, and ADHD-RS) was associated with the remission of insomnia disorder. No differences between ADHD presentations, ADHD treatment or ADHD treatment stability were observed at baseline or during the follow-up period.

Regarding the analysis of insomnia assessment, it is remarkable that less use of mobile device screens in the half hour before bedtime (34.9% vs. 87.5% at 6 months) or a good implementation of sleep hygiene guidelines (92.1% vs. 20.8% at 6 months) were associated with a greater remission of insomnia disorder. Sleep-onset insomnia remained the most frequent insomnia phenotype (70.8%) and 48.3% of subjects had a hypnotic treatment prescription at 6-month follow-up. Benzodiazepines (20.7%), melatonin (17.2%) and antidepressants were the most frequent hypnotic medications. As expected, patients with persistent insomnia disorder had higher scores on the ISI, ESS, and PSQI scales (table 3).

3.3. Logistic regression models

Five logistic regression models were conducted using the variables that retained statistical significance after Bonferroni correction and considering insomnia disorder as the dependent variable (Table 4). The first model evaluated the sociodemographic features at 3 months. Sex and age were independently related to the persistence of insomnia disorder (X² = 23.997; p = <0.0001; Nagelkerke R² = 0.307; constant value 5.318). The second model assessed ADHD characteristics at 3 months, whereby greater severity of ADHD according to ADHD-RS was independently related to a higher prevalence of insomnia disorder (X² = 19.914; p = <0.0001; Nagelkerke R² = 0.296; constant value 3.257). The third model explored variables related to psychological features, and medical and psychiatric comorbidities at 3 months. According to this model, only low scores for PCS and MCS were independently related to persistence of insomnia disorder at 3 months (X² = 68.114; p = <0.0001; Nagelkerke R² = 0.700; constant value 19.058). The fourth logistic regression model analyzed ADHD characteristics at 6 months. It was found that the absence of ADHD improvement according to the CGI-I was related to a greater presence of insomnia disorder (X² = 69.841; p = <0.0001; Nagelkerke R² = 0.675; constant value 2.708). Finally, the relationship between psychological features, medical and psychiatric and insomnia disorder at 6 months were explored using the variables that were statistically significant in the bivariate analysis. Current mood disorder and low scores for MCS were independently associated with greater insomnia disorder prevalence (X² = 65.499; p = <0.0001; Nagelkerke R² = 0.833; constant value 10.011).

4. Discussion

The current study provides new data on insomnia disorder in the adult ADHD population from a longitudinal perspective, especially as regards the relationship between insomnia disorder and the clinical and symptomatic severity of ADHD. The main finding was that insomnia disorder remission was independently associated with a major improvement in the clinical severity of ADHD at 6 months. This is in line with the results published by other authors who argue that the presence of insomnia symptoms worsens the clinical severity of ADHD (Schredl et al., 2007; Wynchank et al., 2018). These results highlight the impact that insomnia disorder has on the clinical severity of adult ADHD, and therefore, the value of systematically exploring and treating insomnia disorder, as it could be considered a predictor of adult ADHD severity.

Regarding ADHD presentations, some studies found no difference between these and insomnia; others noted that the hyperactive/impulsive presentation is correlated with a higher prevalence of insomnia (Yoon et al., 2013). There are no significant differences in our results to suggest any association between the different ADHD presentations and greater remission or persistence of insomnia disorder. This suggests that insomnia disorder persistence could be related to ADHD severity and not to the different ADHD presentations (Corkum et al., 2011). Likewise, no significant differences were identified regarding ADHD pharmacological treatment, both with stimulant and non-stimulant drugs, and ADHD treatment stability.

Concerning somatic diseases, no significant differences were found. However, psychiatric comorbidity was related to greater insomnia disorder persistence. As previous studies highlight, mood disorder (which includes depressive and adjustment disorders) was independently related to a higher prevalence of insomnia disorder at 6 month follow-up, as well as anxiety disorders in the bivariate analysis (Geoffroy et al., 2018; Schredl et al., 2007). Consistent with this, our study shows that patients had worse scores for the BDI and STAI. Furthermore, substance use disorder and personality disorder did not imply a greater risk of insomnia disorder persistence at six months. However, these results must be analyzed with caution since insomnia disorder is associated with a greater prevalence of mood and anxiety disorders (Riemann et al., 2017), and in turn, these disorders are also frequently linked to a greater prevalence of insomnia disorder (Geoffroy et al., 2018; Li et al., 2016)

Furthermore, adult ADHD patients who achieved remission of the insomnia disorder also presented a significant improvement in the perceived mental and physical components of the HRQoL (especially the mental component as it was independently related). Not only insomnia disorder remission, but also a decrease in ADHD severity, would be related to this improvement. These findings are in line with previous research that reported that greater HRQoL was linked to both insomnia disorder and ADHD improvement (Franke et al., 2018; IsHak et al., 2012).

When analyzing insomnia variables, a greater insomnia disorder remission was observed in subjects that implement sleep hygiene rules and behavioral strategies. These measures suggest a set of recommended behaviors to promote good sleep and constitute the initial step in the challenge of dealing with insomnia disorder (Riemann et al., 2017). There are many sleep hygiene rules and behavioral strategies, including: substance abstinence, relaxation, regular exercise, regular sleep/wake times, avoiding clockwatching as well as sleep restriction and stimulus control, and avoiding the use of electronic device screens in the half hour before bedtime (Fossum et al., 2014; Murawski et al., 2018). Our results reveal a significant relationship between less use of electronic device screens before bedtime and improvement of insomnia disorder in the bivariate analysis. However, the association with sleep hygiene rules must be analyzed with caution because the ADHD symptoms themselves could interfere with compliance with these measures. Adult ADHD patients usually show resistance to going to sleep and delayed settling to sleep (Yektaş et al., 2020).

Regarding the prescription of hypnotic pharmacological treatment and insomnia disorder remission, no significant differences were observed in the bivariate analysis of the grouped variables. However, when subcategorizing, significant associations were identified for benzodiazepines, antipsychotics, and anticonvulsants at 6-month evaluation. These results may not be due to the prescription of a certain hypnotic drug but to patients’ adherence to the prescribed hypnotic treatment (DiMatteo, 2004).

Finally, when analyzing sociodemographic features, female and older age were independently associated with persistence of insomnia disorder at 3 months. However, this difference was not observed at 6 months. These findings are consistent with studies conducted in the general population (Reyner et al., 1995; Suh et al., 2018).

Despite the new findings, this study presents some limitations that should be noted. First, it did not use objective or electrophysiological measures of sleep, such as polysomnography or actigraphy. The use of these instruments would make the results stronger. Second, although all patients received psychoeducation on sleep hygiene rules and behavioral strategies in the different visits, a structured cognitive behavioral therapy for insomnia disorder was not performed. Finally, the complex, heterogeneous and bidirectional interaction between adult ADHD and insomnia disorder must be considered when interpreting these results. However, this research also has important strengths. As far as we know, this is the first study to longitudinally evaluate the relationship between adult ADHD and insomnia disorder according to DSM-5 diagnostic criteria. In addition, an optimal set of validated instruments was used in a representative sample of adults with ADHD. Furthermore, the rigorous exclusion and inclusion criteria avoided certain confounding factors such as the exclusion of patients that display or are suspected of other sleep disorders that could be confused with insomnia (e.g., obstructive sleep apnea or circadian rhythm disorder).

In short, while more work has to be done, this study highlights the impact of insomnia disorder remission on the clinical severity of adult ADHD and on the associated psychiatric comorbidities. These results may contribute to a better clinical approach to both disorders and to a better understanding of their complex interactions.

Declaration of competing interests

CF has received fees to give talks for Shire/Takeda and Rubió. CD has no conflict of interest. LG has received fees to give talks for Janssen-Cilag, Lundbeck, Servier, Otsuka and Pfizer. VR received travel awards (train tickets + hotel) for taking part in psychiatric meetings from Shire in the last 3 years. RFPA has received fees to give talks for Exeltis, and Takeda. MC has no conflict of interest. BS has no conflict of interest. MB has received fees to give talks for Janssen-Cilag and Angelini. JARQ was on the speakers’ bureau and/or acted as consultant for Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Medice and Rubió, Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen- Cilag, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió.

Fundings

The research leading to these results has received funding from the Instituto de Salud Carlos III (PI18/01788) and supported by the EU's Horizon 2020 Program (grant nº 667302, CoCA and Grant Nº 728018 Eat2beNICE).