Treatment for Depression and ADHD: Treating Comorbid Mood Disorders Safely

Patients with comorbid depression and ADHD may experience more severe symptoms of each, and require specialized treatment plans that factor in potential side effects, contraindications, and lifestyle considerations. Here is a comprehensive overview of all treatment options, including new therapies like ECT, TMS, and ketamine still being actively studied for treatment of depression and ADHD.

By Roberto Olivardia, Ph.D. Verified Updated on May 9, 2023

A patient in therapy with a doctor, one available treatment for depression.

Comorbid depression and attention deficit hyperactivity disorder (ADHD) present a unique set of risks and challenges. When co-occurring, the conditions’ symptoms manifest more severely than they would in isolation. Sometimes, depression may manifest as a result of ADHD symptoms; this is called secondary depression. Other times, depression manifests independent of ADHD, but its symptoms can still be impacted by it.

For people with mood disorders, having comorbid ADHD is associated with an earlier onset of depression, more frequent hospitalizations due to depression, more recurrent episodes, and higher risk of suicide, among other markers.

Proper management and treatment of both ADHD and depression is, therefore, crucial. Options for patients today include an array of psychological and psychopharmacological treatments, along with newer, cutting-edge approaches. Psychologists, therapists, and psychiatrists should consider the following therapies and medications for treating patients with comorbid ADHD and depression.

Psychological Therapies for ADHD and Depression

As with any treatment, the best approach to treating depression and ADHD depends on the patient’s individual needs. Psychologists and therapists can often treat depression using these four behavioral therapies, or a combination of them.

Cognitive Behavioral Therapy (CBT)

Strong empirical studies show that this therapy is effective for treating patients with depression. In my practice, CBT usually is the first line of approach for psychological therapies.

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CBT targets cognitive distortions by helping patients be mindful of their negative thoughts, and by challenging them to find evidence for them. The behavioral component, in turn, addresses self-destructive, avoidant, and otherwise unproductive behaviors. Patients may be given tools, like anxiety management skills, to help them execute positive behaviors.

CBT, however, is difficult to implement when a patient is experiencing severe depression, which makes it difficult to think clearly and inhibits the therapy from taking proper effect. Psychologists and/or therapists can always return to CBT once the patient’s depression has lifted to the point where they can better process thoughts.

Acceptance and Commitment Therapy (ACT)

ACT teaches some CBT principles, but rather than try to restructure negative thinking as CBT does, ACT directs patients toward passive acknowledgement instead. If a patient has a negative thought, ACT tells them they need not accept it as truth — or put energy into changing it.

ACT also focuses on values. Particularly with depression, patients can feel worthless — like they don’t contribute much or have a place in the world. Many patients with whom I work feel they must be perfect in order to be acceptable, for example. ACT targets this way of thinking by asking patients to recognize and articulate their value systems — and to execute their values through relationships, not accomplishments.

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Interpersonal Therapy (IPT)

Similar in some ways to ACT, IPT falls under traditional psychotherapy or talk therapy, and focuses heavily on the roles that relationships and interpersonal connections play.

Patients undergoing IPT will consider the notion that good relationships can help with depression. They may be led to review their relationships and explore whether certain disrupted relationships may be a cause of depression.

As can be the case with cognitive therapy, IPT may not be effective in patients with severe depression or treatment-resistant depression (TRD). Patients with these conditions, who may literally feel like they are unable to live another day, can be reluctant to process their relationships in this way.

Dialectical Behavior Therapy (DBT)

Originally conceptualized for people with borderline personality disorder, DBT has since been used to address a plethora of brain conditions and disorders, including depression.

DBT is a concrete strategy and skills-based treatment. It centers on four modules — mindfulness, distress tolerance, emotional regulation, and interpersonal effectiveness and assertiveness skills. Mindfulness can be especially helpful for people with ADHD. Patients with ADHD can benefit from being mindful of their potential distractions and of where their thoughts wander, for example.

Like CBT, DBT is another first-line approach for me. I’ve found in my own practice that depressed patients with ADHD take well to DBT because the therapy focuses so heavily on specific skills and strategies that can be put into action instantly. If I have a patient who is in acute distress, I find DBT is the best therapy to use right away, alongside medication. Generally, behaviorally focused therapies, like DBT, tend to be better for addressing acute distress.

Psychopharmacological Treatments for ADHD and Depression

Various medications may be used to treat patients with ADHD and depression. Prior to prescribing, psychiatrists should consider possible interactions with stimulant and/or nonstimulant medications, and the presence of treatment-resistant depression, or TRD. A patient with TRD may not have responded well to one, two, or more antidepressants or other treatments, but may be an ideal candidate for less traditional medications and practices.

Psychiatrists and psychologists should communicate and coordinate with one another on a patient’s treatments. It should not fall on the patient to establish communication between his or her medical providers.

Selective Serotonin Reuptake Inhibitors (SSRIs)

These medications, which allow for more serotonin in the brain, are the most commonly prescribed for patients with depression. SSRIs include:

Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Setraline (Zoloft)

Prozac, or fluoxetine, is more of the classic antidepressant, whereas some of the newer ones, like Luvox or Zoloft, are antidepressants that have anti-anxiety qualities to them.

Patients with obsessive-compulsive disorder (OCD), which is an anxiety disorder, are often prescribed Luvox or Zoloft, for example. The two medications are antidepressants, but they also target that ruminative obsessive nature that can lead to depression.

In adults, the most commonly reported side effects to SSRIs are sexual side effects, ranging from erectile dysfunction or not being able to achieve orgasm. For adolescents, nausea and/or slight weight gain may be reported.

A number of studies have shown that stimulants and nonstimulants do not have an interaction effect with SSRIs, so patients with ADHD and depression can generally take these medications simultaneously without any contraindication.

Tricyclic Antidepressants

Tricyclics target more serotonin and norepinephrine, so depending on the patient, this older class of antidepressants may work best. Tricyclics include:

Amitriptyline
Amoxapine
Desipramine (Norpramin)
Doxepin
Imipramine (Tofranil)

Generally, patients with TRD benefit the most from tricyclics. Most patients, however, are not started on tricyclics because of the many associated side effects, including nausea, dizziness, and anxiety. Still, the experience of living with chronic depression can be so burdensome that patients might be willing to tolerate some negative side effects of tricyclics.

A consideration for people with ADHD: Some tricyclics are known to have an interaction effect with stimulant medications.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are another class of antidepressants that can target one or more neurotransmitters, including serotonin, dopamine, and norepinephrine. Commonly prescribed MAOIs include phenelzine (Nardil) and tranylcypromine (parnate). Some MAOIs may have an interaction effect with ADHD stimulant medications.

Certain foods can cause serious reactions; some patients can’t eat certain cheeses or consume alcohol while taking MAOIs.

I have patients, however, who are more than willing to never eat cheese again if one of the MAOIs work for them when nothing else has.

Atypical Antidepressants and Antipsychotic Medication

Atypical antidepressants include:

Bupropion (Wellbutrin, Forfivo XL, Aplenzin)
Mirtazapine (Remeron)
Trazodone (also for insomnia)
Vortioxetine (Trintellix)

These medications target things that are very different than all of those other classes of depression medication, and are the result of our ever-growing understanding that depression is nuanced and not the same for every patient.

Antipsychotics can help patients with depression by helping to loosen up the sort of concrete, rigid thinking that is common in patients with psychosis, and also with depression. Sometimes, a patient’s thoughts are so fixed that it’s very difficult to get out of that depressed way of thinking.

Antipsychotic medications can also be very useful for patients with particularly severe depression or TRD in augmentation therapy. Aripiprazole (Abilify), Brexipipzole (Rexulti), and Quetiapine (Seroquel XR) are all antipsychotics that are FDA approved as add-on therapies for TRD.

While not FDA-approved, off-label lithium is used by some psychiatrists to augment depression treatment as well.

Cutting Edge Treatments for ADHD and Depression

Electroconvulsive Therapy (ECT)

The public holds a less than favorable perception of ECT, but this treatment can be especially effective for certain patients.

The therapy, which involves placing patients under anesthesia and running electrical currents through the brain via electropads, is particularly useful for people with catatonic depression and/or TRD.

ECT has also been used in treating geriatric depression, and it’s an effective treatment for patients at high risk for suicide, like Caucasian men over the age of 62 — one of the highest suicide groups of all demographics.

As for TRD patients, research indicates that ECT can be a safe, helpful intervention in high-risk situations. A pregnant patient of mine, for example, was struggling with bipolar illness and was at high risk for suicide, but she could not take medication without it interfering with her pregnancy. She underwent electroconvulsive therapy instead, and it was amazingly helpful for her.

ECT sessions take about 10 minutes at most. Patients generally need to undergo two to three ECT sessions a week for about one month, or about six to twelve treatments. Improvement can be seen after about six treatments.

While safer than practices used decades ago, ECT side effects include confusion, retrograde amnesia, nausea, headaches, and muscle pain.

Transcranial Magnetic Stimulation (TMS)

Also called repetitive transcranial magnetic stimulation, this non-invasive treatment stimulates nerve cells in the brain with magnetic fields, targeting parts like the prefrontal cortex that may display abnormally low activity in depressed patients. The mechanism of action is not completely understood, but treatment is done with a wand-like magnetic coil that is placed against the scalp. Patients are awake during the procedure and feel a tapping sensation that corresponds to the pulses from the coil. The FDA permitted marketing of TMS as a treatment for major depression in 2008.

Patients who undergo TMS can proceed with normal activities right after sessions. Some side effects, however, may include scalp discomfort, lightheadedness, slight twitching, and, rarely, seizures. There are no cognitive functioning side effects, like memory loss or confusion, associated with the procedure. This treatment is not indicated for patients with any metal in the body, or for people with psychosis.

TMS is very effective for TRD, studies show. One 2012 study involving 307 patients across 42 different practices found that almost 60% had significantly fewer depressive symptoms after TMS. Another study in 2014 of more than 250 adults found a 30% reduction of depressive symptoms after TMS even after a year follow-up, which is quite significant. Results can last six months, a year, or longer.

Some of my own patients with TRD have had success with TMS. The downside to the treatment, however, is that it’s a significant investment in terms of time and money. Each session is about 20 to 40 minutes, and it can take about 25 to 30 daily sessions before a patient sees results. The total price of treatment is about $10,000. Typically, insurance companies cover a portion of the cost for patients if at least four different antidepressant trials have failed.

Ketamine Infusions

Ketamine is a hallucinogenic drug with properties that can be very useful in treating depression. The drug affects glutamate and GABA — excitatory and inhibitory neurotransmitters of the brain.

Ketamine promotes synaptic connections within the brain for learning and memory, but it can also block other receptors, leading to rapid antidepressant action. Studies have shown that the drug reduces or eliminates very acute or distressing symptoms of depression, including suicidal thoughts. Other studies show that 60 percent or more of patients find relief from depressive symptoms with these infusions.

The drug, still considered experimental, is used for severe cases of treatment-resistant depression. When other antidepressant medications have failed, and/or if there’s acute suicidality, ketamine infusions may be appropriate.

Ketamine is administered via IV for about 40 minutes, with doses determined by the patient’s weight. Patients are conscious during infusions. Some may report odd perceptions or dissociative experiences during the procedure that generally go away afterward. The first session is the most intense, but patients are able to return to normal activities about 30 to 45 minutes post infusion. Some known side effects include nausea, drowsiness, and a feeling of strangeness. Relief typically takes one to three weeks, which is shorter than what is seen with most antidepressants.

Like TMS, ketamine infusions are an investment. Typical treatment spans six infusions over two to four weeks. Infusions are not always covered by insurance, and can cost $300 to $800 per treatment.

The FDA has only approved ketamine as an anesthetic so far, and has not approved it as an antidepressant or for depression treatment. Still, the drug is being used in clinics with a lot of good results and very promising research. Long-term studies, however, are needed. Risk of overuse and dependency, for example, is unknown, though preliminary studies show that this is not common, likely because doses are highly monitored and administered by a doctor.

In 2019, the FDA approved Esketamine, under the brand name Spravato — a nasal spray that contains properties of ketamine in conjunction with an oral antidepressant. This drug is reserved for individuals with TRD only, and was approved after initial trials found the drug to be extremely effective in reducing TRD symptoms. Side effects of this treatment include sedation, some dissociative experiences, nausea, anxiety, vertigo, and vomiting. Health care providers monitor patients for at least two hours after the dose is administered. The medication is also only available under a Risk Evaluation and Mitigation Strategy program, so patients cannot drive or operate heavy machinery for the rest of the day on which they received the drug, among other restrictions.

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