Treating the Hidden Complexities of ADHD

A staggering three-quarters of adults with ADHD have at least one coexisting condition like depression, anxiety, bipolar disorder, obsessive compulsive disorder (OCD), substance use disorder, or an eating disorder.¹ Similarly, up to 80% of children with ADHD also have a co-occurring disorder², which complicates symptom management.

A complex condition requires a thoughtful treatment approach, and multiple diagnoses often require treatment with more than one medication. Unraveling the answers takes time, plus trial and error. Thanks to years of research, however, clinicians are now equipped with highly effective options for addressing tough-to-treat cases of ADHD plus comorbidities.

Use this evidence-based information to begin a conversation with your doctor about treating complex ADHD with combination therapy.

Is Combination Therapy Safe?

The stimulants used to treat ADHD generally have no major drug-to-drug interactions, so they don’t increase the levels of other medications you may be taking, and vice versa. They are safe to use in combination with other medications, including non-stimulants, antidepressants, and antipsychotics. However, some of the non-stimulants, such as atomoxetine (brand name Strattera) or viloxazine (brand name Qelbree), may affect the blood levels of other medications.

Which Condition Do I Treat First?

We generally recommend treating the more sever condition first. If untreated, the symptoms of severe conditions like bipolar or panic disorder can undermine or hijack ADHD treatment. If a patient has mild anxiety, for example, it makes sense to address the ADHD first and then assess any remaining anxiety. Sometimes, anxiety improves when the ADHD is addressed.

Even the most optimized treatment regimen may need to be adjusted over time. After feeling quite stable, a person with ADHD and depression, for example, may feel as though their ADHD is suddenly worse. Worsening depression may worsen the ADHD response. Treating the depression may enhanced the effectiveness of ADHD treatment. Clinicians must take time to sort out such issues when dealing with multiple diagnoses.

[Free Course: The Adult’s Guide to ADHD Treatment]

Anxiety and ADHD

Generally, stimulants don’t worsen anxiety, but they may for some patients. If ADHD symptoms are causing anxiety, stimulants may lessen the anxiety. If the anxiety is unrelated to ADHD, if won’t be improved by stimulants and may, in fact, be exacerbated. A meta-analysis of studies concluded that, in the aggregate, treatment with stimulants significantly reduced the risk of anxiety compared to a placebo.³ The first-line treatment for anxiety is a selective serotonin reuptake inhibitor (SSRI), such as Lexapro, Prozac, or Zoloft.

Atomoxetine is a selective norepinephrine reuptake inhibitor (SNRI) that can effectively treat both anxiety and ADHD with a single medication. There is a caveat: For reasons we don’t yet understand, atomoxetine is not as effective in patients who have already tried a stimulant. If you’re a new patient, talk with your doctor about trying atomoxetine first to treat both the ADHD and the anxiety.

Autism and ADHD

Addressing ADHD in autistic patients may improve functioning dramatically. However, studies show that ADHD medications may cause more side effects and be less effective for autistic people, particularly those with lower intellectual functioning.⁴ Research has found that autistic patients taking ADHD medication experienced a 50% response rate for symptoms including hyperactivity and emotional regulation, which is lower than the 70 to 80% response rate found in children with ADHD who do not have autism.⁵

Begin slowly and monitor closely when increasing the dosage of ADHD medications in autistic patients. It is not uncommon to see an autistic child or adult have a good response to a particular dose of medication, whereas a slightly higher dose may cause many side effects and lessens response. Rather than seeking the “best” ADHD treatment, doctors may aim for good treatment with manageable side effects.

[Read: Interventions for Adult Autism and ADHD]

When severe irritability, aggression, and acute outbursts occur, it may be necessary to stabilize these episodes before addressing ADHD symptoms. Second-generation antipsychotics, such as risperidone or aripiprazole, can work very well to create a calm and controlled context before introducing stimulants or non-stimulants.

OCD and ADHD

Untreated OCD can significantly impede treatment of ADHD, so most practitioners initially prescribe medication and/or psychotherapies like exposure response prevention for OCD, and then tackle the ADHD with stimulant or non-stimulant medication. Both SSRIs and SNRIs are indicated for the treatment of OCD, though SSRIs appear to be more effective. Most medications for ADHD can be used safely in combination with SSRIs/SNRIs.

Depression and ADHD

For children with depression and ADHD, treatment options are limited to an SSRI plus a stimulant or non-stimulant. Adults may benefit from bupropion (brand name Wellbutrin), an antidepressant that is used off-label for ADHD. While depression in adults is commonly treated with SSRIs/SNRIs, some patients report that tricyclic antidepressants help with symptoms of depression and are also quite effective for ADHD.

Eating Disorders and ADHD

Clinicians sometimes hesitate to prescribe ADHD medications to patients with eating disorders due to the common side effect of appetite suppression. These patients’ weight and eating patterns should be monitored closely during treatment, but fear of the side effects should not preclude ADHD treatment, which is shown to improve overall health outcomes.

Though non-stimulants like atomoxetine or viloxazine may be tried first, stimulants need not be ruled out. In fact, the stimulant lisdexamfetamine (brand name Vyvanse) is FDA-approved for the treatment of binge eating disorder as well as ADHD.

Executive Dysfunction and ADHD

The executive function deficits that come with ADHD – difficulties with organization, time management, and sequential thinking – are often burdensome and impairing. For these patients, non-stimulants such as atomoxetine or viloxazine may be used in combination with a stimulant for treating both ADHD and executive function deficits.

Adding an extended-release form of an alpha agonist, like guanfacine or clonidine, to a stimulant is another option that can be useful for executive dysfunction. These medication combinations (e.g., clonidine or guanfacine plus a stimulant) are FDA-approved for treating ADHD in children under 17. They are sometimes used off-label in adults with ADHD.

Research suggests that the Alzheimer’s medication memantine added to the stimulant methylphenidate may improve executive functioning and social cognition, or the capacity to read verbal cues.⁶ This can be especially helpful for autistic children with ADHD.

Comorbid Conditions with ADHD: Next Steps

• Free Tool: The ADDitude Symptom Checker
• Read: What Is Complex ADHD?
• Read: Stimulant, Non-Stimulant, or Both? Combination Therapy for ADHD

Timothy E. Wilens, M.D., is a professor of psychiatry at Harvard Medical School.

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