The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study
Abstract
To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the ADHD symptoms effectively in order to achieve better resolution of anxiety symptoms.
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Many studies have reported improvements in comorbid psychiatric symptoms when ADHD is effectively treated.
“Many studies have reported improvements in comorbid psychiatric symptoms when ADHD is effectively treated.”
From Adult ADHD and comorbid disorders: clinical implications of a dimensional approach (2017) · cites this paper as [114]
Co-administration of SSRIs or SNRIs with stimulants improves functional outcomes in ADHD with comorbid anxiety or depressive symptoms.
“Other studies have demonstrated the efficacy of co-administration of SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) with stimulants on functional outcomes in ADHD with comorbid anxiety or depressive symptoms [113,114].”
From Adult ADHD and comorbid disorders: clinical implications of a dimensional approach (2017) · cites this paper as [114]
Effective treatment of ADHD has been shown to improve comorbid disorders including SUD, bipolar disorder, depression, and anxiety disorders.
“Effective treatment of ADHD has been shown to improve comorbid disorders including SUD [69,95,132], bipolar disorder [17], depression [69], and anxiety disorders [114,133].”
From Adult ADHD and comorbid disorders: clinical implications of a dimensional approach (2017) · cites this paper as [114]
In individuals with anxiety, mixed amphetamine salts are well tolerated as an adjunctive treatment to SSRIs, SNRIs, or other antidepressants.
“In individuals with anxiety, mixed amphetamine salts were found to be well tolerated as an adjunctive treatment to SSRIs, SNRIs, or other antidepressants [114].”
From Adult ADHD and comorbid disorders: clinical implications of a dimensional approach (2017) · cites this paper as [114]
Cites
Ruscio, A. M., Chiu, W. T., Roy-Byrne, P., Stang, P. E., Stein, D. J., Wittchen, H.-U., & Kessler, R. C. (2007) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2006.10.004 · Cited by 145 · see citing works
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Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., Van Ameringen, M., & the Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University (2014) · BMC Psychiatry · doi:10.1186/1471-244x-14-s1-s1 · Cited by 1,090 · see citing works
“In separate open trials, adjunctive atomoxetine [1428] and adjunctive extended release mixed amphetamine salts [1429] significantly improved anxiety symptoms in patients with ADHD and GAD refractory to antidepressants alone.”
BackgroundAdult ADHD and comorbid disorders: clinical implications of a dimensional approach
Katzman, M. A., Bilkey, T. S., Chokka, P. R., Fallu, A., & Klassen, L. J. (2017) · BMC Psychiatry · doi:10.1186/s12888-017-1463-3 · Cited by 732 · see citing works
Aligning the many definitions of treatment resistance in anxiety disorders: A systematic review
Bokma, W. A., Wetzer, G. A. A. M., Gehrels, J. B., Penninx, B. W. J. H., Batelaan, N. M., & Balkom, A. L. J. M. (2019) · Depression and Anxiety · doi:10.1002/da.22895 · Cited by 58 · see citing works
“…& Stahl, 2005; Deligiannidis & Rothschild, 2010; Van Ameringen, Mancini, Patterson, & Stein, 2009), 21 open‐label trials (Gabriel & Violato, 2011; Gabriel, 2010; George et al., 2008; Glue et al., 2017, 2018; Heldt et al., 2003; Heldt et al., 2006; Hoge et al., 2008; Hollifield, Thompson, Ruiz,…”
Adult ADHD and comorbid anxiety and depressive disorders: a review of etiology and treatment
Fu, X., Wu, W., Wu, Y., Liu, X., Liang, W., Wu, R., & Li, Y. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1597559 · Cited by 54 · see citing works
Gabriel, A., & Violato, C. (2011) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-011-0063-1 · Cited by 30 · see citing works
Self-citation
- Authors
- Gabriel, A.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Gabriel, Adel
- Venue
- ADHD Attention Deficit and Hyperactivity Disorders
- Published
- 2010-05-04
- Volume
- 2
- Issue
- 2
- Pages
- 87-92
- ISSN
- 1866-6116 (ISSN-L)
- 1866-6647
- OpenAlex
- W2018293736
- Cited by
- 17
- References
- 1
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 3 · 2017: 2 · 2014: 2 · 2013: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- ADHD Attention Deficit and Hyperactivity Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alberta Health Services
- University of Calgary
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- Adderall XR, adult ADHD, generalized anxiety disorder, anxiety comorbidity, adjunctive therapy, serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, treatment-resistant anxiety, disability, weight loss
- MeSH terms
- Adult, Amphetamines, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Blood Pressure, Body Weight, Delayed-Action Preparations, Drug Resistance, Drug Therapy, Combination, Female, Heart Rate, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors
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