Depression with ADHD

Although ADHD generally is considered a childhood disorder, symptoms can persist into adolescence and adulthood. The prevalence of adulthood ADHD is estimated to be 4%, with 60% of adults having manifested symptoms of ADHD from childhood.8,9 Further, problems associated with ADHD (e.g., social, marital, academic, career, anxiety, depression, smoking, and substance-abuse problems) increase with the transition of patients into adulthood. 

ADHD is rarely encountered without comorbid conditions and often is underdiagnosed. Between 40% and 75% of patients with ADHD will have one or more comorbidities (e.g., learning disabilities, oppositional defiant conduct, anxiety, or depressive disorders).10 It is important to identify other coexisting conditions in patients with ADHD to assist in initial and ongoing selection of treatment. 

Depression. Depressed children and adolescents are often irritable and argumentative. They may also be inattentive and easily distracted. A depressed child therefore potentially looks and behaves much like a child with ADHD. In such cases, one should not immediately make both diagnoses. First, treat the child for depression. If the symptoms of ADHD remain after the depression has resolved, then and only then does it make sense to diagnose and treat ADHD as well. 

The most common side effect of clonidine is drowsiness. This can begin with the very hrst dose and usually goes away after a few weeks. Clonidine s sedating effects can actually be useful when it s taken at bedtime. Insomnia is a common problem for patients with ADHD either as a side effect of stimulants or as a consequence of rebound hyperactivity at night when the daytime dose of stimulant has worn off. Clonidine can help the ADHD patient with insomnia to go to sleep. Other side effects of clonidine include low blood pressure, dizziness, depression, dry mouth, nausea, and slowed heart rate. One important point to remember is that not only does clonidine not cause tics, it can, in fact, relieve tics when they appear in patients with ADHD. 

For example, stimnlants can cause irritability. However, irritability can also resnlt from depression. So it is always important to rule out comorbid depression in the patient with ADHD before discontinuing the stimulant medication. If the irritability does resnlt from depression, then the obvious solution is to add an antidepressant to the stimnlant. Conversely, irritability can also be a symptom of emerging hypomania or mania. 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

Studies at the National Institutes of Health (NIH) have detailed the clinical characteristics of patients in the PANDAS subgroup (Swedo et al., 1998). The rate of neuropsychiatric comorbidity in this population is quite striking. Twenty of the 50 children (40%) met DSM-IV criteria for ADHD and/or oppositional defiant disorder (ODD), 18 (36%) for major depressive disorder, 14 (28%) for overanxious disorder, and 10 (20%) for separation anxiety disorder. Six children (12%) were enuretic, often episodically and closely correlated with periods of OCD and tic exacerbations. Depressive symptoms, ADHD, and separation anxiety disorder also waxed and waned in concert with the OCD/ tic symptoms. In addition, exacerbations of OCD and tics were accompanied frequently by the acute onset of choreiform movements (clinically distinct from chorea), emotional lability and irritability, tactile/sensory defensiveness, motoric hyperactivity, messy handwriting, and symptoms of separation anxiety (Perlmutter et al., 1998 Becker et al., 2000). 

Although tricyclics continue to be used today to treat childhood depression (Zito et ah, 2000), the use in children with ADHD has decreased, most likely because of its association with the sudden deaths of five children (Biederman, 1991). Furthermore, the Physician s Desk Reference (PDR) warns that MPH may inhibit the metabolism of tricyclics, but no such warning exists for DEX or (AMP). Due to the concern that children on this combination of medications are prone to develop more side effects, it is not a recommended form of treatment. Instead, MPH combined with a selective serotonin reuptake inhibitor is preferable for treating a child with ADHD and comorbid depression. 

Venlafaxine is not FDA approved for use in children below the age of 18 however, it has been used in this population as an antidepressant as well as treatment for ADHD. In 1997, a placebo-controlled trial for children and adolescents (n = 32) diagnosed with major depression failed to show a difference between the control and venlafaxine groups (Mandoki, et al., 1997), possibly because of subtherapeutic doses of venlafaxine. A 5-week open trial of venlafaxine (n = 14) in children and adolescents (ages 8-14) with ADHD yielded significant improvements in parent ratings of hyperactivity and impulsivity on the Conners Parent rating scales (Olvera et ah, 1996). 

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. 

The safety and efficacy of combined SSRI and stimulant pharmacotherapy have been addressed in two open studies. Gammon and Brown (1993) reported on the successful addition of fluoxetine to stimulants in the treatment of 32 patients with ADHD with comorbid depressive and anxiety disorders (Gammon and Brown 1993). These children with comorbid conditions had failed to respond to methylphenidate alone. Another report detailed the addition of methylphenidate to SSRI treatment (Findling, 1996). Depressed children and adults with comorbid ADHD were treated with either fluoxetine or sertraline. While depressive symptoms remitted, ADHD symptoms persisted. Methylphenidate was added and successfully treated the ADHD symptoms. In both investigations, the combined treatment was well tolerated. 

Offspring of parents with bipolar disorder have an almost three fold increased risk for developing a mental disorder, and a fourfold risk for an affective disorder, as compared to the offspring of parents with no mental disorder (LaPalme et ah, 1997). Families of patients with early-onset bipolar disorder have higher than expected rates of substance abuse, unipolar depression, antisocial personality, and comorbid bipolar disorder with ADHD. Biederman et al. (2000) have concluded that this comorbid bipolar plus ADHD condition is familial, as evidenced by the fact that the two conditions... 

Daviss, WB. (1999) Efficacy and tolerability of burproprion in boys with ADHD and major depression or dysthymic disorder. Child Adolesc Psychopharmacol Update 1(5) 1,6. 

These authors also found that 65% (New York) and 67% (Ohio) of the sampled medicated patients who received an antipsychotic prescription were not diagnosed with a psychotic disorder. Similarly, 0% and 20% of the sampled medicated patients who received a stimulant medication were not diagnosed with ADHD, and 27% and 42% of the sampled medicated patients who received antidepressants were not diagnosed with major depression, dysthymia, bipolar disorder, or related conditions. In discussing the appropriateness of the medication treatments in the survey, the authors concluded that approximately 10% of the treatments in each sample were deemed inappropriate. 

Meanwhile, as noted earlier in the book, there is the beginning of a backlash, with a recent survey finding that 85% of those interviewed believe that doctors overmedicate children with depression and ADHD and that drugs are harmful to a child s development (Pescosolido et al., 2007). More than half believe that psychiatric medications turn children into zombies. One developmental pediatrician complained about the public s growing skepticism, instead proposing, We need to view... 

Methylphenidate shares the pharmacological properties and the abuse potential of the amphetamines. When given intravenously, it activates psychotic symptoms in schizophrenic patients if administered during the active phase of their illness, but not after remission. It failed to produce a psychotic reaction in most manic or depressed patients or in healthy subjects (27). Adults with childhood-onset ADHD had an earlier onset of psychoactive substance use disorders, independent of any psychiatric co-morbidity (33). However, bipolar disorders conferred a significantly increased risk for early onset psychoactive substance use disorders independent of ADHD. The question arises as to the contribution of stimulant treatment to psychoactive substance use disorders. There were no differences in medicated versus unmedicated adolescents with ADHD in a review of eight outcome studies comprising 580 adolescents briefly treated with stimulants for six months to five years (34). 

A modified-release, once-daily formulation has been evaluated in 282 children with ADHD in a double-blind, placebo-controUed trial for 28 days (37). For core ADHD symptoms, both once-daily modified-release and thrice-daily immediate-release methylphenidate were superior to placebo and not different from each other. A similar percentage of patients reported at least one adverse event with both formulations. The most commonly reported adverse events were headache and upper respiratory infections, followed by abdominal pain, cough, pharyngitis, vomiting, and otitis media. Of these, only headache and abdominal pain were considered to be related to the study medication. One patient withdrew because of depression with modified-release methylphenidate and one because of tics with placebo. Headache occurred in 14%, 5.8%, and 10% of patients taking modified-release methylphenidate, immediate-release methylphenidate, or placebo respectively, and abdominal pain in 6.7%, 5.8%, and 1.0%. Other adverse events included appetite suppression (modified-release methylphenidate) and insomnia (aU three). The results of this study suggest that once-daily modified-release methylphenidate provides efficacy superior to placebo and is not significantly different from thrice-daily immediate-release methylphenidate. 

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. ... 

Cl = 0.05, 10) in patients aged 15-21 years. Although the medications may have contributed to the increased risk of suicide, other factors that can also predispose to suicide, such as depression and antisocial behavior, frequently co-exist with ADHD [56 57 ]. 

There has been a previous report of treatment-related hallucinations with the combination of methylphenidate and fluoxetine in a 14-year-old girl with ADHD depressive disorder [78" ]. The mechanism whereby methylphenidate -I- fluoxetine might cause hallucinations is unclear. 

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