Depression with conduct disorder

The largest juvenile, controlled trial of a TCA reported favorable results with DMI in 62 clinically referred children with ADHD (Biederman et al., 1989). Many of these children had previously failed to respond to psychostimulant treatment. Sixty-eight percent of DMI-treated patients were considered very much or much improved, compared with only 10% of placebo patients (p < 0.001), at an average daily dose of 5 mg/kg. In a further analysis, neither comorbidity with conduct disorder, depression, or anxiety, nor a family history of ADHD yielded differential responses to DMI treatment (Biederman et al., 1993b). In addition, DMI-treated ADHD patients showed a substantial reduction in depressive symptoms compared with placebo-treated patients. 

Children of opiate addicts have been shown to have poorer social, educational and health status and to be at higher risk of abuse than their peers (Keen et al., 2000). However, given the high rates of psychiatric comorbidity (in particular, depression) in opiate-dependent patients (Brooner et al., 1997 Khantzian and Treece, 1985), it may be that some of the increased risk in children stems from this greater parental depression. Nunes et al. (1998) reported higher incidence of conduct disorder and global and social impairment for children of addicts with major depression compared to addicts without depression and controls, but not compared with children of depressed patients without substance use disorders. 

Serotonin-Boosting Antidepressants. Antidepressants that enhance serotonin activity in the brain have also been studied in ADHD. In particular, fluoxetine (Prozac) and the serotonin-selective TCA clomipramine (Anafranil) have been the most extensively evaluated, with mixed success. They provide some benefit for aggression and impulsivity but don t significantly improve the poor attention of ADHD. As a result, the SSRls and other serotonin-boosting antidepressants do not appear to be effective first-line treatments for ADHD. Conversely, depressed patients without ADHD often show improvements in symptoms of concentration and attention when treated with a SSRI. Although SSRls are not widely used in the treatment of ADHD, they may be worthy of consideration in ADHD patients whose impulsivity is not controlled by stimulants alone. Those with comorbid conduct disorder or ODD who are prone to agitation and at times violent outbursts may be helped by the addition of a SSRI. 

Approximately three-quarters of children with OCD have comorbid diagnoses. These include tic disorders (24%-30%) and mood disorders, especially major depression (26%-29%). Riddle and colleagues (1990) found that 38% of children with OCD have other anxiety disorders, while Swedo (1989) more specifically identified increased rates of simple phobias (17%), overanxious disorder (16%), and separation anxiety disorder (7%). Other reported comorbidities include specific developmental disabilities, adjustment disorder with depressed mood, oppositional defiant disorder, attention-deficit hyperactivity disorder (ADHD), conduct disorder, and enuresis/encopresis (Swedo et ah, 1989b Riddle et ah, 1990). 

Children with internalizing disorders such as depression and anxiety are often the best informants about their affective states. However, if children experience depressed or anxious mood as their normal state, no baseline frame of reference is available for comparison. Children and adolescents with externalizing disorders such as ADHD and conduct disorder are often poor informants and may be minimally cooperative with the interview. Since they often deny the existence of a problem and blame others, reports from other informants (parent, school) are essential. 

As may be expected, studies of antidepressants in treatment of ADHD have not shown a differential effect in ADHD children with or without conduct disorder, depression, or anxiety (Biederman et ah, 1993b). While DMI-treated ADHD children showed a substantial reduction in depressive symptoms compared with placebo-treated patients (Biederman et ah, 1989), DMI appears not to be as powerful an antidepressant in children as the SSRls. (Bostic et ah, 1999). The safety and efficacy of combined SSRl and stimulant pharmacotherapy has been addressed in two open studies and is currently being evaluated in a prospective study conducted by the Resarch Units in Pediatric Psychopharmacology (RUPP) Network (B. Vitiello, personal communication). 

Multiple studies have noted the comorbidity between PTSD and depressive disorders (Goenjian et ah, 1995), as well as between PTSD and externalizing disorders (Cuffe et ah, 1994 Glod and Teicher, 1996). Younger children with PTSD may present with classical features of attention-deficit hyperactivity disorder (ADHD), including hyperactivity, impulsivity, restlessness, irritability, and distractibility (Cuffe et ah, 1994 De Beilis and Putnam, 1994 McLeer et ah, 1994 Loof et al., 1995 De Beilis et ah, 1999). More serious externalizing disorders, such as conduct disorder (CD) and oppositional defiant disorder (ODD), are also commonly comorbid with PTSD (Arroyo and Eth, 1985 Steiner et al., 1997). Similarly, the relationship between PTSD and substance use disorders in children has been noted in several studies (Arroyo and Eth, 1985 Brent et al., 1995 Loof et al., 1995). 

PTSD is linked with the increased likelihood of other psychiatric disorders occurring at the same time. Some 88% of men and 79% of women with PTSD meet the criteria for another psychiatric disorder. The most common disorders that men have at the same time as PTSD are alcohol abuse or dependence (51.9%), major depressive episodes (47.9%), conduct disorders (43.3%), and drug abuse and dependence (34.5%). The psychiatric disorders that most frequently cooccur with PTSD in women are major depressive disorders (48.5%), simple phobias (29%), social phobias (28.4%), and alcohol abuse/dependence (27.9%). These statistics may indicate that people with PTSD are more susceptible to psychiatric disturbances in general. 

Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 1991 148 564-577. 

Investigators from the Department of Pediatrics in Johns Hopkins Hospital, after seeing a neonate who had marked leukocytosis temporally related to alprostadil, conducted a retrospective study of neonatal leukocytosis induced by alprostadil in 45 neonates (5). They concluded that alprostadil infusion is a predictable cause of leukocytosis in neonates with congenital heart disease. Alprostadil-induced leukocytosis was especially prominent in three patients with splenic disorders associated with the hetero-taxy syndrome. Many of the other adverse effects of alprostadil, including respiratory depression, hypotension, fever, and lethargy, were also associated with sepsis. The authors considered that it is reasonable to look for sepsis in infants receiving alprostadil, but that it is equally reasonable to withdraw empirical therapy once infection has been ruled out. Leukocytosis associated with alprostadil infusion has not been previously reported and is not listed in the alprostadil package insert. 

Gorman et al. (1987) conducted an open trial of fluoxetine involving 16 patients with panic disorder. They reported, Two of the nonresponders became depressed and had suicidal ideation while taking fluoxetine. Only one of the two had a history of depression (p. 331). Still in the era before recognition of SSRI-induced suicidality, the authors did not comment on this finding. 

It is critical to clarify the diagnosis of ADHD in individuals with these symptoms. Inattention and distractibility can be symptoms of an anxiety disorder, depression, or bipolar disorder. - In other cases, these anxiety or mood disorders can coexist with ADHD, just as learning deficiencies and conduct or oppositional disorders are common comorbid conditions. The presence of multiple comorbid conditions, particularly conduct or oppositional disorder, may increase the likelihood of ADHD chronicity. ... 

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