Ciro Marangoni, MD

ADHD is defined by early onset (before age 12) of persistent (six months or longer) symptoms of inattention and/or hyperactivity and impulsivity that are not consistent with development, causing impairment of normal functioning in at least two settings (home, school). It is the most common psychiatric disorder in children, mostly in school-age boys.

Generally, the diagnosis of ADHD is based on the presentation of impairing levels of attention, hyperactivity, and impulsivity. However, ADHD can present with different symptoms such as irritability, emotional dysregulation, mood lability, low frustration tolerance, low self-esteem, and sleep problems, making the diagnosis difficult because of overlap with mood disorders and personality disorders (

 ADHD onset is generally before age 12 years, with a prevalence of 1.7% to 16%.

 ADHD follows a chronic and unremitting course, persisting into adulthood in half of the cases.

 The hyperactive-impulsive type is associated with trajectories of improvement while the inattentive type is often associated with negative outcomes. ADHD hyperactive type is more prevalent in males, while ADHD inattentive type is more common in girls. The persistence and severity of ADHD during development are associated with adult antisocial and criminal behaviors.

 Hyperactivity in ADHD is characterized by restlessness, fidgeting, talkativeness due to lack of inhibition (but may be sometimes redirected), engaging in risky behaviors (without being aware of the consequences); hyperactivity is present all day and can worsen when prolonged attention or on-task behavior is expected, especially in structured activities.

In children with ADHD, difficulties with attention, resistance to completing homework and poor concentration often interfere with academic achievement. School and social relationships can be impaired by inappropriate behaviors that are accidental, related to inattention, impulsivity, and poor motor coordination. Mood fluctuations are common in children and adolescents with ADHD, with self-esteem worsening over time, but generally do not have dysphoric mood as predominant symptom; mood shifts are usually related to demands of learning and irritability is often worsened by withdrawal from stimulants.

ADHD patients are generally good sleepers, tend to rise quickly, and are alert in minutes; circadian rhythms are normal and there isn’t a decreased need for sleep. Parents can report bedtime resistance but without sleep problems such as middle and late insomnia or nightmares. Psychotic symptoms and hyper-sexual behavior are not part of the ADHD clinical presentation.

 Bipolar disorder has a lifetime prevalence of 2.1% in adults and 1.8% in children

; at least two-thirds of the patients with bipolar disorder report onset before age 18.

 Younger onset is associated with positive family history of mood disorders, comorbidity with anxiety and substance abuse disorders, rapid cycling course, treatment resistance, more hospitalizations, and suicidal behavior.

The episodic course is only one of many courses of illness. Some patients may experience chronic, unremitting symptoms, while other patients may experience weeks or months with attenuated symptoms, or symptom-free intervals. In fact, the requirement of periodicity (recurring episodes of mania and depression) to diagnose BD has often resulted in the misdiagnosis of those with a chronic, non-episodic course of illness.

 The classic manic episode is characterized by the discrete appearance of euphoric/elated mood, talkativeness, decreased need for sleep, impulsivity, hyperactivity, and greater productivity, with rapid transitions to new and more stimulating projects. However, bipolar disorder in youth can also present with dysphoric (or mixed) mania characterized by marked irritability, negative/morbid thoughts, increased impulsivity, risk-taking and aggressive behaviors, and psychomotor agitation as well as a chronic course and ultra-rapid cycling episodes.

Circadian rhythms are altered, resulting in greater fluctuations of energy and activity. Evening hours are preferred with improved mood and energy in the later part of the day, early/middle/late insomnia, and sleep resistance.

Psychosis, including delusions, hallucinations, catatonic features, and bizarre behavior occurs frequently. Suicidality, including morbid ideation, suicidal ideation, and suicide attempts are common in children and adolescents with bipolar disorder as are various forms of aggression (eg, verbal aggression, anger dyscontrol, violent behavior leading to destruction of property or physical aggression).

An increased and precocious interest in sexual content as well as increased sexual behaviors have been described in children and adolescents with bipolar disorder. In such cases of inappropriately precocious sexualized behavior, it is extremely important to rule out any kind of inappropriate exposure to adult material, or sexual abuse.

 According to DSM-5 criteria, a diagnosis of borderline personality disorder should not be made before the age of 18 years; however, diagnosis can be made earlier when symptoms are clear and persistent. The peak frequency of symptoms appears to be at 14 years of age.

Symptom remission (a reduction in the number of symptoms below the diagnostic threshold) is common, especially when diagnosis is made during adolescence.

 However, in spite of the high remission rate, the presence of borderline personality disorder in adolescence is far from harmless.

Borderline personality disorder is highly comorbid with depression, anxiety, substance abuse, and eating disorders, with a high risk for suicide. Suicide risk is higher in the event of co-occurrence with a mood disorder or substance abuse and with increasing number of suicide attempts.

The patient’s functioning is significantly impaired, with school withdrawal, frequent job losses, unstable relationships. Functioning in borderline personality disorder is more highly impaired than in other personality disorders.

 Borderline personality disorder is a mental illness with a chronic and pervasive pattern of instability in interpersonal relationships, self-esteem, and mood, with marked impulsivity. Associated features are increased risk for self-harm, suicide, and transient stress-induced psychotic symptoms. There appear to be two clusters of symptoms, one (characterized by anger and feelings of abandonment) tends to be stable while the other (characterized by self-harm and suicide attempts) is less persistent.

Several features of borderline personality disorder overlap with those of ADHD such as a chronic course, emotional instability, impulsivity and risk taking behaviors, and disturbed interpersonal relationships. Patients with borderline personality disorder may experience a special form of inattention as part of dissociative states when they feel emotionally stressed, particularly in response to feelings of rejection, failure, and loneliness. Inattentive symptoms in ADHD are particularly prominent in situations that lack external stimulation (eg, during boring, routine, or familiar tasks).

Patients with borderline personality disorder have a tendency to resort to self-injurious behavior in order to alleviate tension; ADHD patients are more likely to regulate emotional symptoms through extreme sports, novelty seeking, sexual activity, and aggression.

Stimulants are the cornerstone of pharmacotherapy of ADHD and are helpful in reducing the impact of cognitive deficits on academic performance and social interaction, improving classroom behavior, and increasing time on task. Large-population studies have documented reduced criminal behavior in ADHD adults and decreased car accidents in males with ADHD.

Despite the widespread use of stimulants in pediatric and adult population, the effects of acute exposure during development and chronic exposure in youths and adults are poorly understood. More research is required to assess safety, especially because of the extent of abuse, although several studies suggest relative safety.

Therapeutic approaches are often quite different depending on the primary diagnosis; for instance, mood stabilizing agents and atypical antipsychotics may be beneficial for children with early onset bipolar disorder but are unlikely to enhance attention in children with ADHD and are associated with serious adverse effects.

 On the other hand, stimulants have been shown to be ineffective in the treatment of bipolar disorder. They can cause disruption of sleep and circadian rhythms, and negatively affect persons with bipolar disorder.

 Although some findings indicate that stimulants added to mood stabilizers did not result in manic exacerbation.

In case of comorbidity between ADHD and bipolar disorder, treatment should be directed first to the most severe condition (almost always bipolar disorder). Treatment of ADHD should be considered when ADHD symptoms persist following mood stabilization and have a moderate to severe impact on functioning and quality of life.

Treatment may be needed in stages, for example mood stabilizers for bipolar disorder, followed by stimulants/atomoxetine for ADHD. If a clear diagnosis of ADHD is made, and bipolar disorder is only suspected, then ADHD should be treated first while monitoring potential worsening of bipolar symptoms-stimulants or atomoxetine might exacerbate subthreshold mania. If bipolar symptoms emerge during treatment of ADHD, stop the ADHD treatment until bipolar symptoms have been stabilized and then review the diagnosis of ADHD before considering further treatment.

Psychotherapy is the primary treatment for borderline personality disorder. No fully evidence-based pharmacotherapy exits for core borderline symptoms, although some medications (eg SSRIs, atypical antipsychotics) may be effective for individual symptom domains, such as impulsivity (shared by ADHD and BPD).

Treatment of ADHD should always be considered when treating comorbid personality disorders. If the core syndrome of ADHD improves then patients with comorbid personality disorders are likely to be less distressed, function better in their daily lives, and have more control over their behavior. Moreover, they are more likely to engage and benefit from psychological treatment programs.

Because ADHD, bipolar disorder, and borderline personality disorder share overlapping symptoms, these disorders can be difficult to differentiate and accurately diagnose. Therefore, it is important to take into account other information such as family history, developmental stages and delays, age and type of onset, course of illness, previous and current treatments, type of comorbidity.

ADHD comorbid with bipolar disorder or borderline personality disorder further complicates identification of these conditions and possibly causes patient functioning to be worse than in the presence of only one of these disorders. It is important to accurately diagnose and treat each disorder, comorbid or not, to achieve higher levels of patient functioning.

Dr Marangoni is Attending Psychiatrist, Department of Mental Health, Mater Salutis Hospital, Azienda ULSS 9, Legnago, Italy. 

Dr Marangoni reports no conflicts of interest concerning the subject matter of this article.

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ADHD can present with symptoms such as irritability, mood lability, low frustration tolerance and low self-esteem, making it easily confused with mood disorders and personality disorders.

ADHD, Bipolar Disorder, or Borderline Personality Disorder

Bipolar disorder often presents initially with one or more episodes of major depression, and an episode of mania or hypomania may first occur during treatment with an antidepressant, stimulant, or other agent with mood-elevating effects. Such “switching” of mood into mania, a mixed-state, or psychosis can be dangerous. This switching is particularly prevalent among juveniles and young adults exposed to treatment with an antidepressant or stimulant for a depressive, anxiety, or attention disorder.

 Such pathological shifts of mood and behavior may represent adverse drug actions or a manifestation of undiagnosed bipolar disorder.

DSM-5 now considers that mood elevation with antidepressants justifies the diagnosis of bipolar disorder, whereas earlier editions considered it a drug-induced reaction. Before the development of modern psychopharmacology, distinctions between recurrent unipolar depression and bipolar disorder within a broad “manic-depressive” concept may not have been critical. Currently, however, the diagnostic distinction has considerable clinical significance for prognosis and clinical treatment, including, notably, when and how long to use antidepressants and mood-stabilizing agents.

Recently, we systematically reviewed available research pertaining to antidepressant-associated mood switches and changes of diagnosis from unipolar depression to bipolar disorder, supported by spontaneous mood elevations not associated with treatment.

 Previously, we evaluated rates of spontaneous and antidepressant-associated mood switching among patients with bipolar disorder or unipolar depression.

 Computerized literature searching identified 51 relevant reports involving nearly 100,000 patients with MDD without a history of mania or hypomania who were treated with an antidepressant.

 Mood switching occurred in 8.2% within an average of 2.4 years of treatment, or 3.4% per year. Cumulative risk of mood switching increased up to 24 months of antidepressant treatment. Switching rates were 4.3 times greater among juveniles than adults. Risks tended to be similar the years observed (1968 - 2012), although other findings indicate higher risks with older TCAs than with most newer antidepressants.

We considered 12 studies of patients initially thought to have unipolar MDD who required a new diagnosis of bipolar disorder, usually with verification by occurrence of spontaneous mania or hypomania. Such diagnostic changes occurred in 3.3% within 5.4 years, or 5.6 times less than the rate of mood switching with antidepressants. If the relatively low rates of new bipolar diagnoses are not due to under-reporting, their marked difference from rates of antidepressant-associated mood switching leaves open the possibility that direct pharmacological, mood-elevating actions of antidepressants may be involved in mood switching, in addition to hypothesized “uncovering” or perhaps even “causing” of bipolar disorder. Of particular concern is that these ambiguous possibilities leave specifically uncertain the potential value of long-term treatment with antimanic or putative mood-stabilizing agents.

In general, our findings indicate that mood switching is not uncommon; it occurs in approximately 6% to 8% of patients with unipolar MDD who receive treatment with an antidepressant.

 Switching was much more prevalent in depressed juveniles than in depressed adults, probably because adults with bipolar disorder are more likely to have been recognized and excluded. A particularly intriguing finding was the large apparent excess of antidepressant-associated switching over reported spontaneous diagnostic changes to bipolar disorder. This raises questions about the diagnostic, prognostic, and therapeutic implications of antidepressant-associated reactions.

Depressed patients who become manic during antidepressant treatment appear likely to have other characteristics of bipolar disorder, and prudence requires that they be monitored closely if future trials of antidepressants are considered. Even a single occurrence of mood switching with antidepressant treatment can support a DSM-5 diagnosis of bipolar disorder but may not be sufficient to support indefinitely continued treatment aimed at mood stabilization.

 Indeed, it is not even proved that drugs considered to be mood-stabilizing are highly protective against antidepressant-associated mood switching, although such protection is widely assumed.

 Moreover, there is very limited evidence that prolonged antidepressant treatment provides substantial protection against recurrences of bipolar depression and that it might contribute to emotional instability or rapid cycling.

Our findings also underscore the need for caution in starting antidepressant treatment in a new patient with depression. Several clinical factors may suggest increased risk of either drug-induced switching or spontaneous mania-like responses in depressed patients. They include a family history of bipolar disorder or psychosis, onset before age 25, multiple recurrences of depression within several years, particular temperamental traits (cyclothymic, hyperthymic, or irritable), previous postpartum disorder, psychomotor-retarded depression with hypersomnia and increased appetite, previous excessive activation with a mood-elevating drug, current agitated-dysphoric features, a possible comorbid substance use disorder, and treatment with a TCA or venlafaxine.

An additional clinical implication of switching from depression to mania in patients with bipolar disorder is that following a depression before mania course pattern (versus mania before depression) is associated with less favorable responses to mood-stabilizing agents. This predicts an excess of future depression episodes, with associated risks of substance abuse, disability, and excess mortality from suicide or, later, an intercurrent medical illness.

From the International Consortium for Bipolar Disorder Research, based at McLean Hospital and Harvard Medical School, Boston.

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Mood switching is not uncommon and it is much more prevalent in depressed juveniles than in depressed adults, and there is a large apparent excess of antidepressant-associated switching over reported spontaneous diagnostic changes to bipolar disorder. Details here.

Author | Ciro Marangoni, MD

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