Evidence Review: Stimulant Treatment and Anxiety in Adults With ADHD

Reviewed by Dr. Margarita Krasnova, MD 0009-0004-7926-4312 · Last reviewed 2026-10-05

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Stimulant Treatment and Anxiety in Adults With ADHD

A narrative review of clinical evidence

Abstract

Background: Adults with ADHD and anxiety often face a practical question: will stimulant treatment help their anxiety, leave it unchanged, or make it worse? Changes in anxiety scores and reports of anxiety as a side effect offer different answers.

Objective: To review anxiety symptoms and anxiety-related adverse events during prescribed methylphenidate or amphetamine treatment in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: This narrative review drew on an existing reference collection, supplemented by targeted searches of Europe PMC, original publications, and references in relevant reviews. The final search was conducted on 3 October 2026. Controlled studies, adverse-event reports, and observations in patients with diagnosed anxiety disorders were considered separately. No new meta-analysis or formal certainty assessment was performed.

Findings: Controlled studies reported improvement, worsening, or little difference from placebo in anxiety scores. Many enrolled patients with low anxiety at baseline. Evidence in patients with diagnosed anxiety disorders was limited and included uncontrolled studies and a conference abstract. Anxiety was also reported as an adverse event with both methylphenidate and amphetamine formulations. A published review found an increased risk of anxiety adverse events with extended-release methylphenidate compared with placebo.

Conclusions: Stimulants are not established treatments for anxiety disorders, but anxiety does not invariably worsen during ADHD treatment. The expected benefit for ADHD and the possible effects on anxiety should be assessed separately, with attention to both symptom improvement and adverse effects.

Keywords: adult ADHD; methylphenidate; amphetamine; anxiety; adverse events; narrative review

Introduction

When an adult has both ADHD and anxiety, choosing treatment can be difficult. Better attention and day-to-day functioning may ease some sources of distress, while an anxiety disorder may still need treatment in its own right. Some patients may also develop anxiety or feel more tense after starting a stimulant.

The research is easier to interpret when these possibilities are kept separate. A change in an anxiety rating scale is not the same as an adverse-event report. Nor does improvement in ADHD symptoms necessarily mean that anxiety has improved. Studies also differ in whom they enroll: patients with little anxiety at the outset, patients whose anxiety is already treated, and patients with an active anxiety disorder are not interchangeable populations.

The National Institute for Health and Care Excellence (NICE) recommends the same ADHD medication choices for people with coexisting anxiety disorders as for other people with ADHD. It also recommends slower dose titration and more frequent monitoring when mental health conditions are present. This guidance supports careful treatment of ADHD; it does not establish stimulants as treatments for anxiety disorders. 1

This review examines anxiety ratings in controlled trials, anxiety-related adverse events, and the smaller body of evidence in adults with diagnosed anxiety disorders.

Methods

Literature selection

This narrative review began with an existing reference collection. On 3 October 2026, the supplementary evidence package was checked against the earlier Europe PMC search, which combined terms for adult ADHD, stimulant treatment, and anxiety. Medication terms included methylphenidate, amphetamine, lisdexamfetamine, and dextroamphetamine; anxiety terms included anxiety, anxious, and nervousness. All 236 records returned by that search were retained for review. Targeted searches by author, title, and publication identifier, together with reference checking in relevant reviews, helped identify additional sources.

Sources were selected for their relevance to anxiety outcomes during prescribed stimulant treatment in adults with ADHD. This was a selective literature review, not an exhaustive systematic or scoping review. The search did not cover every database, and screening was not performed independently by two reviewers. Requiring anxiety terms in titles or abstracts can miss studies that report anxiety only as a secondary outcome.

Assessment of the evidence

Placebo-controlled studies were used to examine comparative anxiety outcomes. Studies using another active medication as the comparator, laboratory studies, and uncontrolled observations provided context. Pediatric-only studies, healthy-volunteer studies, and studies of nonmedical stimulant use were not used to infer treatment effects in adults with ADHD. Nonstimulant medications and historical pemoline studies were outside the review's medication scope.

Original articles were consulted when accessible. Otherwise, the review used indexed abstracts or clearly attributed findings from published reviews. The source consulted is identified in Table 1. Findings that could not be verified were not treated as evidence of either benefit or no effect. Mixed-age samples without a confirmed adult-only analysis were considered separately.

Reports from the same trial and repeated measurements were linked where possible. Estimates from published reviews were not counted as additional independent evidence alongside the trials they summarized. No combined participant total was calculated.

The interpretation considered baseline anxiety, treatment setting, comparator, follow-up, missing outcomes, and reporting limitations. No new statistical pooling or formal risk-of-bias or GRADE assessment was undertaken. Any certainty rating quoted belongs to the original review.

Findings

Anxiety symptoms in controlled trials

The controlled studies do not show a consistent effect on anxiety. Some of the apparent differences are understandable when baseline symptoms and treatment settings are considered.

In Biederman and colleagues' six-week trial of osmotic-release oral system methylphenidate (OROS-MPH), 223 of 227 randomized participants were analyzed. Anxiety scores were low at baseline, and the change over time did not differ significantly between treatment groups. Selected patients with stably treated mood or anxiety disorders could participate, so the findings have limited relevance to severe or uncontrolled anxiety. 2

Covey and colleagues studied 255 smokers with ADHD who received nicotine patches and counseling in both groups. The methylphenidate–placebo difference in anxiety was near zero one week after the target quit day and favored methylphenidate at week six. That association became weaker after an additional adjustment for improvement in ADHD symptoms. This does not prove that ADHD improvement caused the anxiety benefit: the adjustment used a change occurring after treatment began and addressed a different statistical question. The smoking-cessation setting also matters when applying the finding elsewhere. 3

In Rösler and colleagues' 24-week trial, methylphenidate improved emotional dysregulation but did not improve anxiety. The result illustrates why emotional lability and anxiety should not be treated as the same outcome. 4 Kaiser and colleagues' ePOD-MPH report likewise found no medication-related benefit on anxiety in its separately analyzed adult subgroup. 5

Weiss and Hechtman's 20-week trial compared dextroamphetamine, paroxetine, their combination, and placebo, alongside psychotherapy. Anxiety scores were low at the start, and the original abstract reported no treatment difference on the Hamilton Anxiety Rating Scale (HAM-A) at the endpoint. 6

Published reviews provide further evidence. Cândido and colleagues reported an imprecise HAM-A estimate from Kuperman's trial and higher anxiety scores during methylphenidate treatment in Kooij's crossover trial. 7 8 9 Castells and colleagues pooled anxiety outcomes from Weiss's trial and a separate lisdexamfetamine driving study. The standardized mean difference was 0.13 (95% CI −0.24 to 0.51; two trials, 110 participants), which did not establish benefit or harm. 10 11 These findings are drawn from the reviews rather than a new analysis of the original data.

Table 1. Selected controlled studies reporting anxiety outcomes

HAM-A: Hamilton Anxiety Rating Scale; BAI: Beck Anxiety Inventory; MPH: methylphenidate; MD: mean difference; SE: standard error; CI: confidence interval. This table summarizes selected evidence rather than every relevant trial. Sample sizes describe different recruitment or analysis stages and should not be added together. A nonsignificant difference does not prove that treatments have equivalent effects.

Adults with diagnosed anxiety disorders

Evidence that directly addresses established anxiety disorders is more limited.

A 2025 conference abstract by Ravindran and colleagues described a placebo-controlled crossover study of PRC-063, an extended-release methylphenidate formulation, in 61 adults. Approximately half had an anxiety disorder. The authors reported no observed anxiety worsening, but did not provide an anxiety-specific treatment estimate or confidence interval. The finding is encouraging but preliminary; it cannot establish equivalent anxiety outcomes across treatment or comorbidity groups. 12

Gabriel's open-label study added mixed amphetamine salts to ongoing antidepressant treatment in 32 adults with ADHD and partially responsive generalized anxiety. Anxiety improved during follow-up. Without a concurrent control group, however, the improvement cannot be attributed confidently to the stimulant. 13

Koyuncu and colleagues retrospectively examined 20 adults with ADHD and social anxiety disorder treated with extended-release methylphenidate. Improvement was reported in 17 patients. Two stopped treatment early because of adverse effects; one experienced anxiety along with other activation symptoms. The lack of a control group limits conclusions about efficacy. 14

These reports are relevant to patients seen in practice, but they do not establish stimulant monotherapy as a treatment for generalized or social anxiety disorder.

Anxiety reported as a side effect

A group can show little change in its average anxiety score while a minority of participants experience new or worsening anxiety. Adverse-event reports help capture that experience, although studies vary in how they collect and label symptoms.

In the four-week SHP465 mixed amphetamine salts trial, anxiety was reported in 6 of 92 participants receiving 12.5 mg/day, 4 of 90 receiving 37.5 mg/day, and 1 of 89 receiving placebo. These denominators refer to the safety population. The counts do not show a steadily increasing risk with dose. 15 In Jain's methylphenidate crossover trial, nervousness was reported in 20% during active treatment and 4% during placebo. Nervousness is relevant to tolerability, but it is not interchangeable with a validated anxiety-scale outcome. 16

Boesen and colleagues' Cochrane review found a higher risk of anxiety adverse events with extended-release methylphenidate than with placebo: risk ratio 2.23 (95% CI 1.40–3.57) across 13 trials and 3,829 participants. The review identified substantial methodological and applicability limitations and rated the evidence very low certainty. Its pooled estimate is a safety signal, not a precise prediction of risk for an individual patient. 17

Table 2. What different anxiety outcomes can tell us

Broad psychiatric adverse-event categories also need care. Biederman's report grouped several symptoms together; that composite cannot be interpreted as an anxiety-only event rate. 2 Similarly, a report of generally good tolerability or no serious adverse events does not establish that anxiety was unaffected.

Findings that need additional context

The COMPAS analysis included 371 adults with ADHD in the available anxiety analysis and combined methylphenidate or placebo with either group psychotherapy or individual clinical management. The report did not provide a numerical methylphenidate-versus-placebo estimate for the SCL-90-R anxiety outcome and reported no significant difference between those medication groups. Because psychotherapy and clinical management were part of the trial design, and the analysis was exploratory with substantial attrition, the result does not isolate the stimulant's contribution with high precision. Observation through week 130 also should not be interpreted as continuous randomized medication exposure. 18

Bloch and colleagues observed changes in anxiety during a cognitive task after methylphenidate. The exploratory design and small additional comparison groups limit what can be inferred about sustained treatment of an anxiety disorder. 19

Bouffard's crossover study reported anxiety improvement, but the available study documentation gives an age range of 17–51 years. Without confirmation of an adult-only analysis, its applicability to a strictly adult population remains uncertain. 7 20 Spencer's 2005 trial assessed anxiety, but the accessible original abstract did not report the anxiety comparison. That result was not used to support the conclusions here. 21

Discussion

What this means in practice

The evidence does not support a simple yes-or-no answer to whether stimulants worsen anxiety. ADHD can improve while anxiety changes little. Anxiety may improve in some settings, but higher anxiety scores and anxiety adverse events have also been reported. The patient's starting symptoms, concurrent treatment, and the outcome being measured all affect interpretation.

Low baseline anxiety is a recurring limitation. A trial enrolling patients with few anxiety symptoms has little room to demonstrate improvement and may tell us relatively little about treating an active anxiety disorder. Nonsignificant comparisons also leave uncertainty: they do not establish equivalence unless the study was designed and sufficiently precise to answer that question.

In practice, it is useful to follow ADHD symptoms, anxiety severity, and new activation symptoms separately. Timing can help: did the change follow treatment initiation or a dose increase, occur alongside sleep disruption, or coincide with a change in another medication? This review cannot establish an optimal management algorithm, but NICE's recommendation for slower titration and more frequent monitoring in patients with anxiety comorbidity provides a practical basis for follow-up. 1

Limitations

The studies differ in medication formulation, baseline anxiety, treatment setting, outcome measures, and follow-up. Anxiety was often a secondary outcome. Selective recruitment, incomplete reporting, attrition, and possible unblinding complicate interpretation. Short trials provide limited information about the longer-term course of an anxiety disorder, while later follow-up does not necessarily preserve the original randomized comparison. The updated evidence search identified additional reports, including a naturalistic longitudinal follow-up, but these did not provide a verified new placebo-controlled anxiety estimate for the main synthesis.

This review also has limits. It used an existing reference collection and targeted searches rather than a comprehensive search of multiple databases and trial registries. Relevant studies may have been missed. Some original full texts were unavailable, so the source level is stated where findings rely on abstracts or published reviews. Independent duplicate extraction and a formal risk-of-bias assessment were not performed. The evidence therefore does not support a definitive ranking of stimulant formulations for their effects on anxiety.

Questions for future research

Trials should recruit adults with clearly characterized anxiety disorders and measure anxiety alongside ADHD symptoms. Reports should include average symptom changes, clinically important worsening, anxiety-related discontinuation, and clear adverse-event definitions. Concomitant medication and psychotherapy should be described, and randomized treatment distinguished from later follow-up. Longer studies with sufficiently precise estimates are needed to determine which patients are more likely to improve, remain unchanged, or experience worsening anxiety.

Conclusion

For adults with ADHD, stimulant treatment may improve, leave unchanged, or worsen anxiety. The controlled evidence does not establish a consistent anxiety benefit, and adverse-event findings show that worsening can occur. Evidence in established anxiety disorders remains limited. Treatment decisions should distinguish the expected benefit for ADHD from the less predictable effects on anxiety, with follow-up that attends to both improvement and harm.

References

1. National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder diagnosis and management. NICE guideline NG87. Recommendations 1.7.18 and 1.7.28. Accessed 5 October 2026. Source

2. Biederman J, Mick E, Spencer T, Surman C, Faraone SV. Is response to OROS-methylphenidate treatment moderated by treatment with antidepressants or psychiatric comorbidity? A secondary analysis from a large randomized double blind study of adults with ADHD. CNS Neurosci Ther. 2012;18(2):126-132. Source

3. Covey LS, Hu MC, Winhusen T, Lima J, Berlin I, Nunes E. Anxiety and Depressed Mood Decline Following Smoking Abstinence in Adult Smokers with Attention Deficit Hyperactivity Disorder. J Subst Abuse Treat. 2015;59:104-108. Source

4. Rösler M, Retz W, Fischer R, et al. Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD. World J Biol Psychiatry. 2010;11(5):709-718. Source

5. Kaiser A, Bottelier MA, de Ruiter MB, et al. Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD. Psychoradiology. 2021;1(3):152-163. Source

6. Weiss M, Hechtman L, Adult ADHD Research Group. A randomized double-blind trial of paroxetine and/or dextroamphetamine and problem-focused therapy for attention-deficit/hyperactivity disorder in adults. J Clin Psychiatry. 2006;67(4):611-619. Source

7. Cândido RCF, Menezes de Padua CA, Golder S, Junqueira DR. Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2021;1:CD013011. Source

8. Kuperman S, Perry PJ, Gaffney GR, et al. Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry. 2001;13(3):129-134. Source

9. Kooij JJ, Burger H, Boonstra AM, Van der Linden PD, Kalma LE, Buitelaar JK. Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial. Psychol Med. 2004;34(6):973-982. Source

10. Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2018;8:CD007813. Source

11. Biederman J, Fried R, Hammerness P, et al. The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: a randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm. J Psychiatr Res. 2012;46(4):484-491. Source

12. Ravindran N, Van Ameringen M, Patterson B, et al. A 14 week randomized placebo controlled cross over study of multilayer release methylphenidate capsules PRC 063 in adult ADHD with and without anxiety disorder comorbidity. Int J Neuropsychopharmacol. 2025;28(Suppl 1):i116. Conference abstract. Source

13. Gabriel A. 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. Atten Defic Hyperact Disord. 2010;2(2):87-92. Source

14. Koyuncu A, Çelebi F, Ertekin E, Kök BE, Tükel R. Extended-release methylphenidate monotherapy in patients with comorbid social anxiety disorder and adult attention-deficit/hyperactivity disorder: retrospective case series. Ther Adv Psychopharmacol. 2017;7(11):241-247. Source

15. Weisler RH, Greenbaum M, Arnold V, et al. Efficacy and Safety of SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled, Forced-Dose Clinical Study. CNS Drugs. 2017;31(8):685-697. Source

16. Jain U, Hechtman L, Weiss M, et al. Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2007;68(2):268-277. Source

17. Boesen K, Paludan-Müller AS, Gøtzsche PC, Jørgensen KJ. Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev. 2022;2:CD012857. Source

18. López-Pinar C, Selaskowski B, Braun N, et al. Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial. Psychiatry Res. 2023;330:115610. Source

19. Bloch Y, Aviram S, Segev A, et al. Methylphenidate Reduces State Anxiety During a Continuous Performance Test That Distinguishes Adult ADHD Patients From Controls. J Atten Disord. 2017;21(1):46-51. Source

20. Bouffard R, Hechtman L, Minde K, Iaboni-Kassab F. The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder. Can J Psychiatry. 2003;48(8):546-554. Source

21. Spencer T, Biederman J, Wilens T, et al. A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57(5):456-463. Source

Suggested citation

Krasnova M. Evidence Review: Stimulant Treatment and Anxiety in Adults With ADHD margaritakrasnovamd.com. Last reviewed 2026-10-05. Available at: https://margaritakrasnovamd.com/evidence-review/adhd-stimulants-anxiety-adults.html