Treatments for Depression and ADHD: New and Forthcoming Approaches

Expert answers to your questions about depression treatments, alternative non-pharmacological approaches, rates of MDD and ADHD, treatment concerns regarding youth, and more.

clinician and patient, doctor talking to patient, medication

November 13, 2023

Rising rates of depression — a condition that often accompanies ADHD and other health concerns — have earned well-deserved concern and attention. Here, Nelson M. Handal, M.D., DFAPA, reviews what we know about major depressive disorder and ADHD, explains the latest treatment options for depression, and touches on alternative treatments and therapies that may hold promise for future use.

Q: What do we know about rates of ADHD and comorbid depression and mood disorders?

There is significant comorbidity between ADHD, major depressive disorder (MDD), and other mood disorders across all age groups. About 15% of children and adolescents with ADHD also have MDD, and anywhere from 7% to 17% of youth with ADHD also have bipolar disorder, according to our group’s review of available literature.1 2 In adults with ADHD, roughly 20% have MDD, and anywhere from 7% to 18% have bipolar disorder.3 About 25% of individuals with bipolar disorder that started in adulthood have ADHD, and the ADHD overlap is much higher — from 80% to 97% — when bipolar disorder begins in childhood.4

Females with ADHD are at greater risk — by 2.5 times — for MDD compared to females without ADHD.5 In older adults, ADHD is associated with increased risk for depression.6

Q: What explains the relationship between ADHD, depression, and mood disorders?

Many factors are at play. One of them may be the inherent challenges that come with living with ADHD — especially when ADHD is undiagnosed, untreated, or poorly treated. Another factor could be adverse life events, which adults with ADHD and depression appear to experience at significant rates. Twenty percent to 70% of individuals with ADHD have experienced adverse life events, and anywhere from 35% to 50% of adults with ADHD report experiencing depressive symptoms, recurrent brief depression, or fully developed depressive episodes.7

Q: What are the newest treatments for depression, and what’s in store for the future?

[Read: How Undiagnosed ADHD Triggers Depression and Anxiety]

The field of depression treatment is making huge advances. In addition to SSRIs, SNRIs, MAOIs, therapy, and other treatments that have long been in use, the latest treatments for depression include the following:

  • Spravato (esketamine, made from ketamine) is a nasal spray treatment approved in 2019 to treat adults with treatment-resistant depression (TRD) and depressive symptoms in adults with MDD with suicidal thoughts or actions.
  • Vraylar (cariprazine) was already an approved medication for bipolar disorder, and it was approved as an adjunctive treatment with antidepressant therapy for the treatment of MDD in 2022. Vraylar is a partial agonist, and modulates dopamine, serotonin, and other neurotransmitters.
  • Auvelity (dextromethorphan-bupropion) received approval to treat MDD in adults in 2022.
  • Zurzuvae (zuranolone) is a rapid-acting oral treatment that was approved to treat postpartum depression (PPD) in August 2023. Though it was approved for the treatment of PPD, zuranolone was rejected by the FDA for the treatment of MDD.

The pipeline is also bursting with antidepressants. A 2022 review of phase II and III clinical trial data identified nine antidepressant compounds — including psychedelics like psilocybin8 — that show positive results for the treatment of MDD or treatment-resistant depression.

Q: What options exist today for patients who do not respond to pharmacological treatment?

Trans-cranial magnetic stimulation (TMS) is a good option for individuals with depression who have not responded to one or two medicines. With TMS, an electromagnetic coil is applied to the head that sends electromagnetic impulses to a specific area of the brain.

[Read: Go “Low and Slow” to Avert and Avoid SSRI Side Effects]

If a patient cannot tolerate TMS or if their insurance doesn’t cover the treatment, we will occasionally refer patients to electroconvulsive therapy (ECT). While an option, it isn’t as effective as other available treatments.

Some individuals may see better results from being on multiple antidepressant interventions at a time. Some of my patients have done well on TMS, Spravato, and other antidepressants simultaneously.

Q: What should parents make of black box warnings associated with SSRIs as they consider treatment for their children and teens with depression?

Is it true that SSRIs can cause emergent suicide thoughts? In adolescents, absolutely. In children, it can happen. Side effects of these medications are always important to consider when deciding treatment.

As practitioners, we have to look at every detail of a patient before prescribing antidepressants. In order to prescribe an SSRI to a patient experiencing depression, for instance, I have to know if they have a family history of bipolar disorder, which may complicate treatment.

I communicate to the parents of my young patients that there are two goals with any treatment. One is efficacy, and the other is tolerance. To that end, we start on a low dose and go up slowly because of tolerance and possible side effects, including suicidal thoughts. Low and slow prevents these issues, and we see patients after about three weeks to assess.

Q: Is there any reason that someone with ADHD and comorbid depression would favor taking a non-stimulant over a stimulant to treat ADHD in this context?

If a patient were “activated” while on stimulants, that could be one reason they might favor a non-stimulant. Having a comorbid mood disorder or cardiovascular problems (like high blood pressure or cardiomyopathy) may also limit patients to non-stimulants to treat ADHD.

Overall, a complete evaluation and understanding of a patient’s ADHD and comorbid conditions is crucial to formulate a successful treatment plan. That includes asking the patient about family history with conditions, prior responses and side effects experienced on ADHD medications if previously taken (we do pharmacogenetic testing when needed), and even if they have any stigma related to medication use. While stimulants have been around for decades and are one the most studied medications in pharmacology, there is still much stigma surrounding their use that could interfere with a patient’s short- and long-term success.

Treatments for Depression: Next Steps

The content for this article was derived from the ADDitude webinar titled, “New Insights Into and Treatments for Comorbid Depression” [Video Replay & Podcast #456] with Nelson M. Handal, M.D., DFAPA, which was broadcast on May 24, 2023.

Since 1998, ADDitude has worked to provide ADHD education and guidance through webinars, newsletters, community engagement, and its groundbreaking magazine. To support ADDitude’s mission, please consider subscribing. Your readership and support help make our content and outreach possible. Thank you.

View Article Sources

1 Larson, K., Russ, S. A., Kahn, R. S., & Halfon, N. (2011). Patterns of comorbidity, functioning, and service use for US children with ADHD, 2007. Pediatrics, 127(3), 462–470.

2 Klein, R. G., Mannuzza, S., Olazagasti, M. A., Roizen, E., Hutchison, J. A., Lashua, E. C., & Castellanos, F. X. (2012). Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Archives of general psychiatry, 69(12), 1295–1303.

3 Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C. K., Demler, O., Faraone, S. V., Greenhill, L. L., Howes, M. J., Secnik, K., Spencer, T., Ustun, T. B., Walters, E. E., & Zaslavsky, A. M. (2006). The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. The American journal of psychiatry, 163(4), 716–723.

4 Skirrow, C., Hosang, G. M., Farmer, A. E., & Asherson, P. (2012). An update on the debated association between ADHD and bipolar disorder across the lifespan. Journal of affective disorders, 141(2-3), 143–159.

5 Biederman, J., Ball, S. W., Monuteaux, M. C., Mick, E., Spencer, T. J., McCREARY, M., Cote, M., & Faraone, S. V. (2008). New insights into the comorbidity between ADHD and major depression in adolescent and young adult females. Journal of the American Academy of Child and Adolescent Psychiatry, 47(4), 426–434.

6 Michielsen, M., Comijs, H. C., Semeijn, E. J., Beekman, A. T., Deeg, D. J., & Sandra Kooij, J. J. (2013). The comorbidity of anxiety and depressive symptoms in older adults with attention-deficit/hyperactivity disorder: a longitudinal study. Journal of affective disorders, 148(2-3), 220–227.

7 Semeijn, E. J., Comijs, H. C., Kooij, J. J., Michielsen, M., Beekman, A. T., & Deeg, D. J. (2015). The role of adverse life events on depression in older adults with ADHD. Journal of affective disorders, 174, 574–579.

8 Sakurai, H., Yonezawa, K., Tani, H., Mimura, M., Bauer, M., & Uchida, H. (2022). Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry. Pharmacopsychiatry, 55(4), 193–202.