Differential diagnosis

It is important to consider that many who report distractibility, poor concentration or problems at school do not have ADHD (Reference CarlatCarlat 2007). It is also unlikely that an adult who reports no problems with schoolwork or attention as a child has ADHD (Reference CarlatCarlat 2007). Alternative diagnoses such as depression, a mixed episode, anxiety disorders, substance misuse and personality disorder need to be considered. Inattention or poor concentration commonly occur in depression and mixed states, together with the usual features of these syndromes. It can also be helpful to ask whether the patient usually has trouble with concentration when they are well, and if this has been continuous since childhood. Most people who report that their concentration normalises with their emotional state do not have ADHD (Reference CarlatCarlat 2007). Medical and psychiatric differential diagnoses for ADHD are shown in Box 3.

Adults with ADHD present with slightly different characteristics than children. Hyperactive symptoms tend to decrease with age and adults manifest fewer externalising symptoms (Reference Klassen, Katzman and ChokkaKlassen 2010). Symptoms may take the form of:

1. • hyperactivity, which may be reported as ‘nervousness’; symptoms can also be verbal, such as excessive talking;

2. • impulsivity, which may present as a tendency to interrupt others in social interactions, aggressive driving, impulsive spending, or the commencement of multiple projects, none of which are finished;

3. • poor attention, manifesting as careless mistakes, impaired planning, poor attention to detail or failure to listen when spoken to; this may also be reported as trouble concentrating (e.g. watching television, reading books);

4. • mood can be very reactive, and fluctuations can last from hours to a few days.

These symptoms are associated with psychosocial and occupational problems. Adults with ADHD are twice as likely to be arrested, have a twofold increased risk of divorce, a 78% greater risk of being unemployed, and accumulate more speeding tickets than the general population (Reference Janakiraman and BenningJanakiramann 2010; Reference Klassen, Katzman and ChokkaKlassen 2010).

Diagnostic complexities can arise given that there are a number of shared symptoms between ADHD and hypomania/mania (Table 1). Differentiating ADHD from bipolar II disorder, bipolar-spectrum disorders and episodes with mixed symptomatology can be difficult, as irritability, excessive activity, talkativeness, distractability, increased activity, physical restlessness, impulsive behaviour and poor judgement can be caused by ADHD (Reference Klassen, Katzman and ChokkaKlassen 2010). Nonetheless, many of the core symptoms of classical mania and hypomania (delusions of grandeur, euphoria, decreased need for sleep, racing thoughts, hypersexuality and psychotic symptoms) are not present in ADHD alone (Reference SchefferScheffer 2007).

TABLE 1 Attention-deficit hyperactivity disorder (ADHD) v. mania/hypomania

There are a few key characteristics that assist in determining whether ADHD is present in someone with bipolar disorder. The most obvious contrasting features of ADHD and bipolar disorder lie in their time of onset and longitudinal course. Attention-deficit hyperactivity disorder has an early onset, usually occurring before the age of 7, whereas a childhood onset of bipolar disorder is rare (Reference ParkerParker 2010). Attention-deficit hyperactivity disorder is pervasive such that patients usually report continuous symptoms, whereas bipolar disorder tends to be episodic (Reference ParkerParker 2010). Regarding age at onset, a history of ADHD can be established when school records, collateral history and the history taken from the patient support this diagnosis in childhood and before the onset of symptoms of mania or hypomania. One would also expect to see continuing symptoms of ADHD in someone with both ADHD and bipolar disorder in the absence of episodes of hypomania, mania or depression. This can be somewhat more complicated than it might initially seem, as recent studies have challenged the traditional view that bipolar disorder is purely episodic. In longitudinal studies over a period of years, people with bipolar disorder experienced symptoms for about half of follow-up weeks, but these were predominantly depressive rather than manic, and were mostly subsyndromal (Reference Judd, Akiskal and SchettlerJudd 2002, Reference Judd, Akiskal and Schettler2003). Additionally, attention deficits can occur in bipolar disorder even during euthymia, as discussed above (Reference Clark and GoodwinClark 2004). These factors being taken into consideration, subsyndromal affective symptoms and bipolar disorder-related attention deficits are unlikely to be present continuously from childhood in the pattern typical of ADHD.

With respect to the differential diagnosis for a depressive presentation, it is helpful to consider that ADHD can be associated with a degree of dysphoria as a consequence of frustration with failures in life. Dysphoria arising from dismay over the psychosocial impact of ADHD symptoms is more likely to respond to ADHD treatment than to antidepressants, and can be distinguished from depression based on the absence of psychomotor changes, fatigue, sleep changes, anhedonia and suicidality, which are common in depression but not ADHD (Reference SchefferScheffer 2007).

Rating scales

There are a number of rating scales for ADHD in adults, including the Conners’ Adult ADHD Rating Scale, the Brown Attention-Deficit Disorder Scale for Adults, the Wender Utah Rating Scale, the ADHD Rating Scales, the Current Symptoms Scale, and the Adult ADHD Self-Report Scale (Reference Murphy and AdlerMurphy 2004). These can be helpful as an adjunct to a thorough clinical assessment and in monitoring response to treatment, but have significant limitations. Self-report scales have questionable reliability, and no rating scale alone provides sufficient evidence to make a diagnosis of ADHD, as false positives may occur (Reference Murphy and AdlerMurphy 2004). No current scales have been extensively evaluated in people with comorbid ADHD and bipolar disorder. Neuropsychological testing may be of use, both in assessing impairments associated with ADHD and in those who may have neuropsychological deficits from other causes.

General principles

There is currently a lack of empirical data to guide the treatment of ADHD in association with bipolar disorder, so patients should be treated on a case-by-case basis. We suggest a cautious approach. Clear-cut outcomes for treatment should be determined and monitored rather than trialling medication without targeting specific symptoms. When diagnoses are unequivocal and there is clear functional impairment, pharmacotherapy is justified. If a diagnosis is less clear-cut and functional impairment is less severe, a trial of psychosocial treatment with close monitoring may be a more reasonable approach.

Generally speaking, there are two broad approaches to managing independent comorbid conditions: sequential and hierarchical. The sequential approach involves identifying and managing the first temporal condition, and then managing any conditions that remain. The hierarchical approach involves determining the most clinically important factor, managing it, and then considering whether the less important condition has been corrected, or remains and requires management (Reference ParkerParker 2010).

The risks of untreated bipolar disorder are generally more severe than those of untreated ADHD, so we recommend adopting a hierarchical approach and treating bipolar disorder first (Box 4). In some cases, symptoms that appear to be due to ADHD may respond to bipolar disorder treatment, making additional treatment for ADHD unnecessary. Bipolar disorder treatment should encompass medication, education, psychological and social interventions, with the aim of full control of symptoms where possible (Reference ParkerParker 2010).

Once bipolar disorder has been treated, a hierarchical approach can then be taken with the treatment of remaining comorbidities, including ADHD, treating the most destabilising illness first and then continuing in a step-wise fashion to manage the remaining conditions (Reference SchefferScheffer 2007). Where possible, it is best to introduce new medications one at a time in order to better assess the effect of each one. Comorbid anxiety disorders should probably be treated before ADHD, as stimulants could potentially worsen these conditions. In individuals who misuse substances, it may be beneficial to commence treatment for this at the same time as treatment for ADHD and bipolar disorder. Treatment of substance misuse may improve ADHD and bipolar disorder symptoms, and ADHD treatment may reduce the severity of comorbid substance misuse (Reference Klassen, Katzman and ChokkaKlassen 2010).

Pharmacotherapy

One of the most significant challenges in managing comorbid ADHD and bipolar disorder is that it is not entirely clear what effect stimulants have on bipolar disorder. There are a number of case reports of stimulant-induced mania, yet other studies, albeit small and uncontrolled, suggest that stimulants do not usually worsen mania and may even have some antimanic effects (Reference Hegerl, Himmerich and EngmannHegerl 2010; Reference Hensch, Himmerich and HegerlHensch 2010). For example, one retrospective review of 16 patients with bipolar disorder (only 5 of whom also had ADHD) showed that methylphenidate improved concentration without causing mania over a mean treatment duration of 14 months (Reference Lydon and El-MallakhLydon 2006). One factor in these conflicting findings is that a manic switch can occur after many months of stability (Reference SchefferScheffer 2007), so trials with long follow-up periods are needed to elucidate the risk of stimulant-induced mania in those with ADHD and bipolar disorder. There is some evidence that bupropion reduces symptoms of ADHD and depression without causing mania (Reference Wilens, Prince and SpencerWilens 2003).

Given the paucity and conflicting findings of the research available, it is probably best to use stimulants only in carefully selected patients to reduce comorbid ADHD symptoms, and to avoid using stimulants without a mood stabiliser or in those who are not strictly adherent to drug regimes. One should also be circumspect about stimulant use in people with comorbid anxiety disorders, as anxiety symptoms may be exacerbated by stimulants. The patient and their carers should be warned of the possibility of mania as a result of stimulant use, and made aware of early warning symptoms (Reference MorrissMorriss 2004). If symptoms of mania occur, a break from the stimulant and reassessment of the mood stabiliser regimen should be undertaken (Reference SchefferScheffer 2007). Clearly, other agents that make the symptoms worse (e.g. antidepressants triggering mania) should also be ceased (Reference SchefferScheffer 2007). In situations where stimulants have a significant positive effect on ADHD symptoms but are causing breakthrough manic symptoms, possible strategies include increasing the mood stabiliser dose or prescribing short breaks from the stimulant on weekends (Reference SchefferScheffer 2007).

One should enquire about a personal or family history of cardiac disease before beginning a stimulant. Stimulants may induce or exacerbate cardiac arrhythmias and hypertension. An electrocardiogram should be considered prior to treatment, especially in those over 40 years (Reference NewcornNewcorn 2007). Medication history should include over-the-counter stimulants and caffeine, as methylphenidate, amphetamines and atomoxetine can accentuate their effects (Reference NewcornNewcorn 2007).

Psychosocial treatments

Psychosocial treatments should be used for every patient with comorbid ADHD and bipolar disorder. Psychotherapeutic approaches to bipolar disorder that have shown benefits include psychoeducation, cognitive–behavioural therapy, interpersonal and social rhythm therapy, and family therapy (Reference Lauder, Berk and CastleLauder 2010). There is emerging evidence for cognitive–behavioural therapy and meta-cognitive therapy for adults with ADHD (Reference Knight, Rooney and Chronis-TuscanoKnight 2008; Reference Solanto, Marks and WassersteinSolanto 2010). Meta-cognitive therapy incorporates cognitive–behavioural principles and aims to change styles of thinking in order to promote the development of executive self-management skills. Although no studies on psychological treatments for combined ADHD and bipolar disorder have been published to our knowledge, it makes sense to utilise the psychological treatments that have been established for non-comorbid ADHD and bipolar disorder as appropriate to the patient’s clinical state, needs and preferences. Psychological techniques may need to be adjusted for people with ADHD, using, for example, shorter and more frequent sessions. Neuropsychological testing can enable psychological work to be adjusted according to an individual’s deficits.

A psychodynamic understanding may also be helpful. In an age with effective biological treatments and diagnostic criteria that focus on behavioural phenomena rather than on a person’s mental experience, it has become easy to forget that symptoms frequently have meaning and occur as part of the person’s life. People with ADHD often have an impaired ability to soothe themselves because their attention impairment has affected their ability to internalise and maintain comforting parental introjects (Reference GabbardGabbard 2005). Failure to meet parental and societal expectations can lead to feelings of inadequacy and incompetence, resulting in the development of a defensive grandiosity, which could be confused with mania (Reference GabbardGabbard 2005). Adults with ADHD may fail to recognise interpersonal cues, and can develop stereotypical ways of relating to others as a defence against anxiety in interpersonal interactions (Reference GabbardGabbard 2005). Exploring the mental experience of the patient, meaning and context can be helpful diagnostically and in tailoring a treatment plan to an individual; this can also have a therapeutic effect in itself.