ADHD is the most common behavioral disorder of childhood. Uncomplicated ADHD is a fairly straightforward disorder to diagnose and treat, but significant numbers of children and adolescents with ADHD have comorbid disorders. In these situations, the differential diagnosis is much more difficult and treatment can be quite complex. Over the last several decades, considerable research has been done to determine the prevalence of various comorbid diagnoses in children with ADHD. The most common comorbid diagnosis is that of oppositional defiant disorder, which can affect up to 60% of both boys and girls with ADHD. A smaller percentage of around 20% children with ADHD may develop conduct disorder. The prevalence rates for mood and anxiety disorders are somewhat more variable and less well defined, but at least a third of children with ADHD may develop an anxiety disorder. The rate of major depressive disorder (MDD) among children with ADHD has been estimated to range from 10 to 30%. Figures for the prevalence of mania on children with ADHD are somewhat more difficult to come by. Biederman and his colleagues found that up to 16% of their sample of ADHD children met criteria for mania.  In contrast, U.S. National Institute of Mental Health Multimodal Treatment Study of Children with  ADHD (MTA) did not find it necessary to exclude any children. Nonetheless, the MTA study did find a subgroup of ADHD children who showed very high levels of mood lability, aggression and hyperactivity. There is often disagreement among clinicians as to how many of these types of children truly have bipolar disorder.

Oppositional defiant disorder (ODD) is a pattern of negativistic, hostile and defiant behavior.  Children with ODD lose their tempers easily, argue with and frequently defy adults, and show irritating behavior toward peers. They tend to remain angry and resentful for long periods of time and are often spiteful or vindictive. ODD varies greatly in its severity. It is important to note that both ODD and conduct disorder are descriptive diagnosis that do not imply any particular etiology. This is in contrast to the diagnosis of ADHD which is a primarily neuro-biological condition. ODD may be secondary to ADHD —a child with ADHD may be so impulsive that he reacts with anger and poor judgment to any adult request or to any stressor. Therefore it is important that when the child meets criteria for both ADHD and ODD, the clinician should consider the ADHD to be primary. A number of studies have now shown that oppositional behaviors improved with treatment of the ADHD. This is true for all of effective treatments for ADHD, including both stimulants and atomoxetine.

Conduct disorder is a much more severe disorder, because it involves aggression and antisocial behavior. Children with ADHD and conduct disorder can be differentiated from those with ADHD alone by a number of factors. ADHD children with comorbid ODD/CD are also more likely to have learning disorders, particularly in the area of language. They are more likely to have a family history of antisocial behavior and are at greater risk for developing delinquent behavior during adolescence. Children with ADHD alone have a higher risk of developing substance-abuse disorders as adults, but children with ADHD and comorbid ODD/CD often began experimentation with illegal substances during early adolescence.

It is important to bear in mind that children with ADHD and comorbid ODD/CD respond as well to stimulants as children with ADHD alone. There is no evidence that stimulants or other medications used to treat ADHD increase aggression at appropriate doses except in very rare circumstances. There has also been considerable research on whether treatment with stimulants itself is a risk factor for substance abuse. Timothy Wilens and his colleagues reviewed a number of studies examining the rate of substance-abuse disorders in children with ADHD as a function of their stimulant treatment history. In fact, children with ADHD who never received treatment with medication had a higher rate of substance abuse than those who received treatment. This suggests that effective treatment of the ADHD may actually prevent the development of later substance-abuse disorders.

If oppositional and aggressive behaviors persist after the ADHD has been adequately treated, then several approaches should be considered. The clinician should consider adding a behavior management program. This usually consists of identifying key oppositional behaviors that need to be targeted —for instance a child needs to improve on behaviors such as not hitting a sibling, doing things first-time asked and doing his homework promptly. Each day he receives points from the parent based on how well he has performed these tasks. His weekly allowance is then based on how many points he earns during the week. If he earns a particularly high level of points, then some special privilege is awarded. In contrast, if the number of points earned is extremely low, then some restriction from weekend activities is called for. Alpha agonists such as clonidine or guanfacine have been combined with stimulant medication to treat temper outbursts and aggression. Adverse events such as dizziness and low blood pressure may occur however, and parents should be warned about these risks. In severe situations, where the aggressive behavior is dangerous to the patient or to others, then mood stabilizing or atypical antipsychotic medication may be appropriate. I will return to this topic after our discussion of ADHD and bipolar disorder.

Studies examining the prevalence of depressive disorders in children and adolescents with ADHD have yielded variable results. Roughly 11% of the patient's in the MTA of ADHD study met criteria for major depressive disorder. In most studies of children with depression the rate of ADHD is approximately 30%. When a child presents with both ADHD and MDD the clinician faces the dilemma as to which condition to treat the first. The Texas Children's Medication Algorithm Project (CMAP) recommends that the clinician assess each disorder and determine which is the most severe; this disorder should be the focus of initial psychopharmacologic management.   After the ADHD has been successfully treated, the clinician should assess whether the depressive symptoms remain problematic. If so, the clinician should begin treatment of the depression, usually with a serotonin reuptake inhibitor or institute a psychosocial intervention. In contrast, if the major depressive episode is quite severe (with a high level of the neurovegetative signs and/or suicidal ideation), then an antidepressant treatment should be the initial intervention. If the ADHD symptoms persist after the depression has remitted, then a stimulant may be added to the antidepressant regimen.

Up to one third of children with ADHD may also have a comorbid anxiety disorder. Quite often, these anxiety symptoms are mild in severity, and are related to the high level of stress that the child feels due to the dysfunction in his life. If the child's worries are confined to the consequences of his ADHD behaviors, then the clinician can be reasonably optimistic that these anxiety symptoms will remit once the ADHD is under control. In other cases, however, the child will suffer from intense anxiety including phobias, obsessive-compulsive symptoms, or high levels of generalized anxiety associated with physiological symptoms such as racing heart, muscle tension or trouble sleeping. The Texas Children's Algorithm Project (CMAP) recommended two different approaches for dealing with this situation. Atomoxetine has been shown to be effective for the treatment of both anxiety and ADHD, so it may be considered an initial treatment in this situation. Alternatively, the child may be treated with a stimulant, but if the anxiety symptoms do not remit after treatment of the ADHD, then a serotonin reuptake inhibitor can be added to the stimulant in the treatment of both anxiety and depressive disorders. One should not lose track of the fact that psychotherapy, particularly cognitive behavioral psychotherapy, is a very effective treatment for these disorders. Thus it is equally acceptable to combine pharmacologic treatment of the ADHD with a psychosocial intervention for the anxiety.

The treatment of the comorbidity of ADHD and bipolar disorder is perhaps one of the most difficult problems in child and adolescent psychiatry. For the purposes of this paper, we will include in the bipolar spectrum those patients with severe mood lability and aggression who may not have all of the classic DSM-IV symptoms of bipolar disorder. If a patient with ADHD is floridly manic, then mood stabilization is the priority and treatment of the ADHD should be deferred until this has occurred. In childhood and adolescence, lithium and valproate have been studied in controlled trials. Considerable open trial data suggests the efficacy of atypical antipsychotics.  Atypical antipsychotics have the advantage that they have a rapid onset of action and very flexible dosing. They generally require less laboratory monitoring than lithium or valproate.  Nonetheless they are associated with weight gain, a risk of diabetes, metabolic syndrome and elevated cholesterol. Children on atypical antipsychotics require monitoring of weight, and serum lipids at least twice a year.  When mood stabilization has been achieved then treatment of the ADHD can progress. In situations in which the diagnosis of the mania is less clear or in doubt, then the initial treatment should address the ADHD. If the putative mania symptoms resolve with successful treatment of the ADHD then it is unlikely that the child was in fact suffering from a bipolar disorder. In contrast, if the child's inattentive impulsive and mood symptoms do not resolve with treatment of the ADHD or if the child worsens, then the clinician may move to treatment with anti-manic agents.

The final issue to address is the comorbidity of tics and ADHD. At one time, it was believed that tics were an absolute contraindication to stimulant treatment. Recent evidence has shown, however, that there is no statistically significant difference between placebo and stimulants in terms of their propensity to cause tics in children with comorbid ADHD and tic disorders.  However, most clinicians will encounter patients with comorbid ADHD and tics who have an increase in tics when they are started on a stimulant medication. In this situation, the clinician should try an alternative medication for the ADHD in an effort to control the ADHD symptoms without exacerbating the tics. In some situations however, the patient only responds to a stimulant in terms of the ADHD, but the stimulant worsens the number or severity of the tics.  If this occurs the clinician should consider adding an alpha-agonist to the stimulant medication.  Only in the most severe situations, should the clinician consider adding an atypical antipsychotic.

In summary ADHD can be comorbid with a wide range of disorders. Fortunately there is an equally diverse array of treatment approaches that the clinician can apply to these situations. As a result, we can substantially help these difficult patients.

* Steven R. Pliszka M.D.,Professor and Vice Chair; Chief, Division of Child & Adolescent Psychiatry, Dept. of Psychiatry, University of Texas Health Science Center at San Antonio , San Antonio, Texas, USA.
Dr. Armando Filomeno, who met Dr. Pliszka at CHADD's 17th Annual International Conference in Dallas, USA, October 2005, thanks the distinguished professional for this excellent article which he translated into Spanish for APDA's electronic newsletter nº 12, issued on June 28, 2006.