Addressing treatment hurdles in adults with late-onset attention-deficit/hyperactivity disorder: a detailed case report

Attention-deficit/hyperactivity disorder (ADHD) is recognized as the most prevalent psychiatric disorder in children and is categorized as a neurodevelopmental alteration that can persist into adulthood [1]. The symptoms include inattention, hyperactivity, and impulsivity [2]. ADHD often coexists with mood instability and anxiety, which may not only be attributed to ADHD itself, but also indicate mixed mood symptoms along the bipolar spectrum. Mixed states involve features of both mania and depression but may not fully meet the criteria for bipolar disorder Type I or II [3]. Mood disorders are often classified this way, but emerging research emphasizes that mood dysregulation is not limited to these categories suggesting a broader spectrum where inattention, anxiety, and mood dysregulation intersect, complicating diagnosis and treatment [4]. Recognizing the unique clinical signs and symptoms in comorbidity between ADHD and mixed symptoms along bipolar spectrum is crucial, underscoring the importance of early diagnosis to improve the patient prognosis [5]. Early diagnosis is associated with a reduction in adverse life outcomes and decreased clinical and economic burden, due to significantly higher annual healthcare costs and the complex management needs of this patient population [6, 7].

Despite its prevalence, ADHD in adults is often underestimated, primarily due to the diagnostic challenges presented in adulthood [8]. These challenges arise from the different symptom presentation observed in adults compared to children. For instance, while, children often exhibit overt hyperactivity, adults tend to experience internal restlessness [9]. Moreover, adults typically exhibit attention deficits as their primary symptom, which hinders their ability to perform tasks requiring sustained focus and functionality [10]. Additionally, they tend to exhibit less emotional control compared to children [9, 11] and dysfunction of inhibitory control may differ, which is important to differential diagnosis [12].

Diagnosing ADHD poses challenges due to the existence of comorbid disorders, which complicates the diagnostic assessment as some symptoms can be common to both conditions [13]. Additionally, most ADHD diagnostic tools rely on self-reports, that can lead to subjective bias and are influenced by a patient's ability to self-assess accurately, including the Adult ADHD Self-Report Scale (ASRS), Conners' Rating Scales, and the ADHD Rating Scale (ADHD-RS). The diagnostic criteria for adult ADHD also require evidence of impairment across multiple domains of functioning [14]. Efforts have been made to develop more direct diagnostic tools for ADHD. Genome-wide association studies (GWASs) have identified common genetic markers associated with the condition, which may be useful in predicting ADHD in combination with other screening tools, making the diagnosis of ADHD more precise [15].

ADHD has a strong genetic influence and follows a polygenic inheritance pattern [16, 17]. Certain risk alleles can affect brain structural and functional alterations in brain regions [18]. For example, the genotypic variability in DRD4 may affect brain structure and/or activity, indicating a particular developmental trajectory in cortical brain structure related to adult outcomes of ADHD [17]. Other studies have shown whole-brain morphometry reductions in gray matter volume, and functional magnetic resonance imaging studies have shown decreased activation in the left superior frontal gyrus and the corpus callosum [19].

Recent research has delved into the neural mechanisms underlying the remission and persistence of ADHD. Activity in the inferior frontal cortex plays a crucial role in ADHD remission, with partial normalization observed in the cerebellar and parietal regions [20, 21]. Subcortical anomalies in the right caudate are associated with a childhood history of ADHD and are present even in those who have remitted as adults [22].

Cortico-cerebellar processes are linked to adult ADHD outcomes, and anomalies in the inferior frontal cortex related to inhibition are tied to persistent hyperactivity and impulsivity symptoms [23]. Prefrontal anomalies during inhibition tasks have been identified, along with late activations in the cerebellar and precuneal/inferior parietal regions related to adult outcomes [24]. Neuronal activity during inhibitory processes has been studied to understand ADHD outcomes in adulthood, providing insights for targeted interventions. Persistent subcortical abnormalities, particularly in the caudate, contribute to the onset of ADHD and remain unchanged through development and recovery, impacting cognitive processes [22, 25]. Understanding these biomarkers is essential for identifying individuals likely to display ADHD symptoms in adulthood and for developing personalized treatments tailored to the diverse clinical presentations of ADHD [26, 27].

Pharmacological treatments for ADHD include stimulant and non-stimulant medications, aiming to balance neurotransmitters in the brain, thus improving attention and reducing hyperactive and impulsive behaviors [28]. Stimulant medications, such as methylphenidate and amphetamines, increase dopamine and norepinephrine levels [29]. Non-stimulant medications, such as atomoxetine and guanfacine, primarily affect norepinephrine levels [30]. Non-stimulants offer a viable alternative for those who do not respond well to stimulants or experience adverse effects, with longer-lasting impacts beneficial for managing comorbid disorders like anxiety [30]. Methylphenidate and atomoxetine similarly improve executive functions in people with ADHD [31]. Additionally, research shows that cognitive-behavioral therapy (CBT) significantly reduces ADHD symptoms, improves emotional regulation, and enhances overall functioning, particularly for adults managing ADHD long-term [32].

This case report underscores the significance of ADHD diagnosis as a valuable tool for understanding and clinically managing this neurobehavioral disorder. It provides a comprehensive account of the history, assessment, treatment, and outcomes of a specific individual diagnosed with ADHD in adulthood. The report adheres to the CARE criteria [33], offering valuable insights for fellow health professionals, enhancing their understanding of the diverse clinical presentations and the intricacies of diagnosis. Written informed consent was obtained from the patient for publication of this case report and any accompanying data in accordance with the Declaration of Helsinki. Additionally, this study complies with the specific requirements set by the Institutional Review Board of the Ethics Committee of the Federal University of Ceará (UFC) on the 8th of March, 2023.

A 49-year-old married male patient, with three children and a high school education, who owns a residence, was referred by his spouse due to recurrent anxiety episodes and persistent depressive moods. Despite an initial diagnosis of major depressive disorder, his mood symptoms fluctuated between depressive lows and periods of heightened irritability and impulsivity, suggesting mixed features along the bipolar spectrum. The patient’s inattention, impulsivity, and mood dysregulation persisted despite trials of venlafaxine-XR, escitalopram plus aripiprazole, and escitalopram plus lithium, raising concerns about whether his mood symptoms were purely depressive or part of a broader bipolar mood instability. Treatment with divalproate (1000 mg daily) was initiated for mood stabilization, along with escitalopram (20 mg daily) and bupropion (300 mg daily). This presentation aligns with recent studies suggesting that many patients with ADHD may also have mood instability characteristic of a bipolar spectrum condition, where mood shifts are frequent but do not necessarily reach full manic or hypomanic episodes [7, 34]. During his physical examination, the patient was alert and oriented, well-groomed, and cooperative. There were no signs of acute distress. His pupils were equal, round, and reactive to light, with intact extraocular movements and no visual abnormalities noted. Hearing was normal to whispered voice. No abnormalities were noted in the cardiovascular and respiratory systems. The abdomen showed no tenderness or masses. Reflexes were intact, and sensory and motor functions were normal.

During clinical interview, the patient exhibited diagnostic criteria specified in the DSM-5 for the combined type of ADHD (Table 1) and the Adult ADHD Self-Report Scale (ASRS-18) was employed to evaluate the ADHD symptoms [35]. These symptoms were evident from childhood, characterized by a gradual development of personal responsibility, markedly subpar academic performance, impaired peer relationships, familial stress, and conflicts. In adolescence and adulthood, these symptoms persisted, manifesting as inadequate job performance, challenges in anger and frustration management within relationships, financial mismanagement, issues in romantic or marital relationships (failure to honor commitments), sleep disturbances, frequent awakenings, resulting in diurnal fatigue, and an unhealthy lifestyle (sedentary behavior, poor nutrition, excessive engagement with TV, video games, and the internet).

The patient underwent several assessments, including the Battery for Attention Assessment (BPA-2), Functional Impairment Scale (EPF-TDAH), ADHD Scale (ETDAH—AD), Rey Complex Figure Test, Nonverbal Intelligence Test (G-36), and Concentrated Attention Test (D2-R). The results revealed that the patient scores in the superior average range for nonverbal intelligence but below average in memory, perception, and executive functions. This indicates significant impairments in visual perception, task management, and processing speed. General attention scores were within the average range. The patient exhibits inattention, showing difficulty with task completion, planning, and organization. He also has deficits in self-regulation of attention, motivation, and action, struggling with goal setting and problem-solving. Impulsivity issues were noted, with low impulse inhibition and social difficulties. Hyperactivity was indicated by unstable behavior and poor work quality. Emotionally, the patient experiences a depressed mood, social isolation, and severe impairments in academic and professional functioning.

He was started on lisdexamfetamine with the dosage titrated up to 70 mg daily and cognitive-behavioral therapy (CBT) was employed to cultivate skills for symptom management across multiple domains, targeting effective coping strategies and proficient problem-solving, aligning with the core objectives of this therapeutic approach. The initial protocol addressed latent demands expressed by the patient concerning disorganization (“I tend to leave items scattered throughout the house”), planning difficulties (“I struggle to manage my day effectively”), emotional regulation challenges (“I find it challenging to derive satisfaction from work”), procrastination tendencies (“I tend to delay tasks until the last moment to avoid confrontations”), and inhibitory control deficits (“I become excessively irate and employ profanity when subjected to honking”). Post-intervention, the patient acknowledged the difficulties concerning academic and occupational performance, relationships, and long-term life objectives. Central to the patient's belief system are pervasive sentiments of inadequacy and worthlessness, coupled with a simplistic interpretation of emotions, portraying a perpetually racing mind. The Palographic test resulted in 8.4 mm, indicating increased impulsivity.

After treatment, the patient exhibited significant improvements in managing anger and impulsivity, better time management, and effective problem-solving strategies. However, challenges remain, particularly in information processing speed and attention, with specific difficulties in learning and mathematical calculations. Cognitive stimulation exercises have notably enhanced working memory, while metacognition has increased self-awareness of dysfunctional thoughts, allowing for more adaptative thinking.

The patient has also made considerable progress in reflecting on actions before executing them, which has improved inhibitory control. Nonetheless, certain negative triggers lead to impulsive decisions, thoughtless comments, inappropriate behaviors, disrupted activities, and recurrent self-control lapses. Executive function issues persist, impacting time perception, task forgetfulness, difficulties in establishing and adhering to routines. He experiences irritable outbursts when thwarted, resulting in shouting and physical expressions of frustration. Personal disorganization and suboptimal hygiene standards remain concerns, with his vehicle and possessions often in disarray. Additionally, he faces challenges in goal planning and attainment.

ADHD is a neurodevelopmental disorder characterized by symptoms that primarily manifest during childhood, often leading to diagnoses before adulthood [36]. This case report involves a 49-year-old referred due to persistent anxiety and depressive mood, subsequently diagnosed with ADHD. Upon further evaluation, his diagnosis was revised to ADHD with comorbid bipolar spectrum disorder.

The presence of mixed mood symptoms, such as irritability, anxiety, and rapid mood fluctuations, complicates the clinical picture of ADHD. While initially diagnosed with depression and anxiety, the patient’s symptom profile—including restlessness, mood shifts, and irritability—suggested a broader mood dysregulation disorder, possibly linked to bipolar spectrum features [37]. This aligns with emerging research, which suggests that bipolar disorder is not limited to Types I and II but can include subthreshold symptoms that overlap with ADHD, leading to treatment resistance if misdiagnosed [4, 38, 39].

A stepwise approach to treatment, where mood stabilization is achieved before addressing ADHD symptoms, is critical for minimizing the risks associated with treating these comorbid conditions. This approach allows for better management of both mood and attention symptoms [40]. Additionally, combining pharmacological treatments with CBT alleviates core symptoms and enhances CBT's effectiveness. This approach also boosts executive function, sleep, emotional regulation and quality of life [41, 42]. Despite the benefits of medication, adults with ADHD often report ongoing impairments, highlighting the importance of integrating non-pharmacological interventions for better treatment adherence and long-term outcomes [43].

The socio-economic burden of ADHD underscores significant global challenges, impacting nearly every aspect of life, especially for undiagnosed or untreated adults. Effective treatments can alleviate these burdens and improve outcomes [36]. Studies highlight the common issue of late ADHD diagnoses despite childhood symptoms, such as poor school performance and social difficulties [44‐46]. This patient exhibited childhood signs, including delayed personal responsibility, below-average school performance, poor peer relationships, stress, and family conflicts. Research indicates that adolescents with ADHD often persist with symptoms into adulthood [47]. Untreated adolescents with ADHD show more impulsive behavior then peers without ADHD or in remission, as this patient [48, 49].

Despite advancements in improving mood and enhancing concentration, deficits in working memory, executive function, and emotional regulation persist. Lack treatment results in significant work and interpersonal impairments, linked to the severity ADHD symptoms and comorbid conditions. Even with medication, residual symptoms cause notable difficulties [50, 51]. Disorganization and distractibility are among the most frequent and clinically significant residual symptoms in adults with ADHD, affecting life satisfaction for this population [52].

Timely diagnosis is a crucial for improving prognosis and reducing risks associated with ADHD [5‐7]. This patient’s delayed diagnosis, despite early symptoms, resulted in long-term cognitive and emotional regulation deficits. ADHD is often underreported, due to inadequate early care, family support, and non-specific diagnostic elements. Symptoms like inattention, impulsivity, and hyperactivity can be confused with depression, anxiety, or bipolar disorder [46, 53]. Diagnostic criteria developed for children may underestimate adult ADHD incidence [53‐56].

Late diagnosis of adult ADHD leads to prolonged unmanaged symptoms and significant life impairments. Advancements in diagnostic tools, understanding genetic and neurobiological factors, and using technology for symptom monitoring and management are crucial for effective treatment strategies. Further research is needed to achieve these goals.

The study, while limited by its single-case design and reliance on self-reported measures, offers valuable insights into diagnosing and treating adult ADHD. As evidenced by the case, treatments for ADHD must be personalized, recognizing the underlying bipolar spectrum features that may coexist with attention deficits. It emphasizes the need for integrated treatment approaches and suggests that combining CBT with pharmacological treatments is effective. Despite the potential for bias and the need for larger, more diverse samples in future research, the findings can help clinicians develop comprehensive treatment plans that address core symptoms and comorbid conditions, ultimately improving patient outcomes and quality of life.

This case underscores the importance of recognizing mood instability and mixed states within the bipolar spectrum in patients with ADHD. Traditional treatment approaches focusing solely on ADHD symptoms or depression may miss critical aspects of mood dysregulation, leading to treatment resistance. A comprehensive, personalized approach, integrating both mood stabilizers and stimulants, as well as CBT tailored to manage both ADHD and mood symptoms, is essential for improving patient outcomes. Future research directions include exploring genetic and neurobiological markers to enhance diagnostic precision and developing personalized treatment plans that cater to the diverse clinical presentations of ADHD in adults. Moreover, future research should focus on advancements in diagnostic tools and methodologies to better understand the progression and impact of early diagnosis on long-term outcomes. This comprehensive approach aims to mitigate the socio-economic burden of ADHD and optimize therapeutic outcomes for affected individuals throughout their lifespan.