Attention-Deficit/Hyperactivity Disorder (ADHD)

Caffeine has stimulant-like properties that may improve attention and executive functioning in individuals with ADHD. A study in rodent models showed that caffeine improved memory and attention through enhanced dopaminergic signaling in the prefrontal cortex, paralleling the effects of prescription stimulants (Pandolfo et al., 2013). Human trials are limited, but a double-blind study in children with ADHD found that caffeine modestly improved behavior and attention, although not as effectively as methylphenidate (Lara et al., 2010). Nevertheless, caffeine may disrupt sleep—a significant concern for individuals with ADHD, as sleep impairment exacerbates core symptoms.

Depression

Caffeine’s psychostimulant properties and dopaminergic activation suggest potential antidepressant effects. A large prospective cohort study found that women who consumed ≥4 cups of caffeinated coffee daily had a 20% reduced risk of depression compared to those consuming little or none (Lucas et al., 2011). This protective effect is attributed to caffeine’s anti-inflammatory properties and its modulation of brain-derived neurotrophic factor (BDNF) (Kaster et al., 2015). However, excessive use may mask depressive symptoms or contribute to mood instability, especially when withdrawal effects are misinterpreted as depressive episodes.

Anxiety Disorders

Caffeine is a known anxiogenic agent, particularly in susceptible individuals. At high doses (e.g., >400 mg/day), caffeine can induce symptoms consistent with generalized anxiety or panic disorder, including restlessness, insomnia, palpitations, and irritability (Boulenger et al., 1984). A randomized trial demonstrated that patients with panic disorder were significantly more sensitive to caffeine’s stimulatory effects, exhibiting heightened cardiovascular and subjective anxiety responses (Charney et al., 1985). Clinical guidelines generally recommend limiting or avoiding caffeine in individuals with anxiety disorders.

Bipolar Disorder

Caffeine’s effects on mood stability in bipolar disorder are complex. While it may transiently alleviate depressive symptoms, its stimulant properties can disrupt sleep and potentially trigger manic or hypomanic episodes. Disrupted circadian rhythms are central to bipolar pathophysiology, and caffeine—especially when consumed late in the day—can exacerbate this vulnerability (Wehr et al., 1987). A study by Leibenluft and colleagues found that individuals with bipolar disorder frequently use caffeine during depressive phases but reported increased agitation during manic episodes (Leibenluft et al., 1996). Clinical prudence suggests moderating caffeine intake, especially during manic or mixed states.

Psychosis and Schizophrenia

Individuals with schizophrenia often consume caffeine at rates exceeding those of the general population. This may reflect attempts to counteract sedation from antipsychotic medications or cognitive dulling (Gurpegui et al., 2004). However, caffeine’s dopaminergic effects pose theoretical risks of exacerbating psychotic symptoms. Lucas et al. (1990) found that high caffeine intake was associated with increased positive symptoms, particularly in patients taking clozapine. Furthermore, caffeine is metabolized by cytochrome P450 1A2, the same enzyme responsible for metabolizing several antipsychotics, including olanzapine and clozapine, potentially leading to drug interactions (Carrillo et al., 2000).

Substance Use Disorders

Caffeine interacts with reward pathways implicated in substance use. While moderate caffeine use may not pose harm, energy drink consumption (often containing high caffeine doses) has been associated with increased risk of alcohol and stimulant misuse among adolescents and young adults (Arria et al., 2011). Caffeine also carries its own dependence potential, with recognized withdrawal symptoms such as headache, fatigue, and irritability (Juliano & Griffiths, 2004). Screening for problematic use patterns is warranted, particularly in individuals with comorbid SUDs.

Conclusion

Caffeine is a psychoactive substance with condition-specific effects on mental health. While it may offer mild symptomatic relief in ADHD and depression, it can also exacerbate symptoms in anxiety, bipolar disorder, and psychosis, or complicate treatment in substance use disorders. Mental health and primary care providers should assess individual caffeine consumption patterns, explore patient motivations for use, and provide tailored guidance based on psychiatric diagnosis, comorbidities, and medication interactions.

References

1. Vázquez JC, et al. Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies. Nutrients. 2022;14(4):739. https://doi.org/10.3390/nu14040739News-Medical
2. Grosso G, et al. Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies. Mol Nutr Food Res. 2016;60(1):223-234. https://doi.org/10.1002/mnfr.201500620
3. Lara DR. Caffeine, mental health, and psychiatric disorders. J Alzheimers Dis. 2010;20 Suppl 1:S239-48. doi: 10.3233/JAD-2010-1378. PMID: 20164571. https://journals.sagepub.com/doi/abs/10.3233/JAD-2010-1378
4. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004;176(1):1-29. https://doi.org/10.1007/s00213-004-2000-x
5. Charney DS, Heninger GR, Jatlow PI. Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry. 1985 Mar;42(3):233-43. doi: 10.1001/archpsyc.1985.01790260027003. PMID: 2983630. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/493529
6. Lucas PB, Pickar D, Kelsoe J, Rapaport M, Pato C, Hommer D. Effects of the acute administration of caffeine in patients with schizophrenia. Biol Psychiatry. 1990 Jul 1;28(1):35-40. doi: 10.1016/0006-3223(90)90429-6. PMID: 2375945. https://linkinghub.elsevier.com/retrieve/pii/0006322390904296
7. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet. 2000 Aug;39(2):127-53. doi: 10.2165/00003088-200039020-00004. PMID: 10976659. Gurpegui M, et al. Caffeine consumption in schizophrenia: associations with clinical and sociodemographic features. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(5):945-951. https://link.springer.com/article/10.2165/00003088-200039020-00004
8. Meredith SE, et al. Caffeine Use Disorder: A Comprehensive Review and Research Agenda. J Caffeine Res. 2013;3(3):114-130. https://doi.org/10.1089/jcr.2013.0016
9. Fredholm BB, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83-133. https://pubmed.ncbi.nlm.nih.gov/10049999/

AUTHOR:

Shawn Singh Sidhu, MD, DFAPA, DFAACAP

Co-Medical Director, Vista Hill Foundation

Vista Hill Native American SmartCare Program

Stimulants work by increasing the levels of norepinephrine and dopamine in the frontal cortex. They also stimulate adrenergic receptors in the heart and blood vessels, leading to small increases in resting heart rate and blood pressure—on average, an increase of <10 beats per minute for heart rate and <5 mm Hg for both systolic and diastolic blood pressure. A minority (5-15%) of patients experience larger increases. The existing evidence on long-term cardiovascular risks of stimulants is mixed. Some studies have shown no increased risk, while others have cited an increased risk for arrhythmias, cerebrovascular disease, hypertension, ischemic heart disease, heart failure, pulmonary hypertension, and/or sudden cardiac death. Overall, existing studies are of limited quality and relatively short duration.

A 2024 case-control study by Zhang et al. examined the long-term (up to 14 years) cardiovascular effects of stimulants in 278, 027 individuals aged 6–64 years in Sweden. The results suggested that long-term use of ADHD medications was associated with an increased risk of hypertension and arterial disease. Each additional year of medication use was associated with an average of 4% increased risk of cardiovascular disease. The increase in risk was highest during the first three years of treatment and thereafter stabilized. Reassuringly, the study did not observe any statistically significant increases in the risk for arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

When determining whether a stimulant is the right course of action for a particular patient with ADHD, providers must balance the potential benefits against these risks. Proper treatment of ADHD can improve educational, occupational, and social outcomes. Additionally, stimulants are associated with a decrease in unintentional physical injuries and deaths, substance use disorders, and criminal acts. These medications are highly effective, with response rates of 65-75% and an effect size of 1.0. Therefore, in a generally healthy child or adolescent without cardiac risk factors, stimulant medication should still be considered the first-line treatment for ADHD, and no routine cardiac evaluation is necessary. Consultation with cardiology may be warranted prior to stimulant initiation in cases of complex congenital heart disease or symptoms suggesting significant cardiovascular issues, such as severe palpitations, fainting, exercise intolerance (not accounted for by obesity), or a strong family history of sudden death.

To improve the cardiovascular safety of stimulant use, providers should have an extensive discussion with patients and parents about the risks, including cardiovascular risks, benefits, and alternatives of the medication. Screening each child for factors that increase cardiovascular risk, including personal and family cardiovascular history, is essential. Additionally, monitoring pulse and blood pressure at baseline and regularly throughout treatment is recommended. Psychopharmacology should be just one part of a comprehensive treatment plan, which may also include psychoeducation, behavioral therapy, lifestyle modifications including diet and exercise, linkage with community supports, and school resources. If stimulants are not an option, providers can explore alternative treatment options, such as nonstimulant medications (though selective norepinephrine receptor inhibitors and alpha 2 agonists also have cardiovascular risks to consider) or behavioral therapy without medications. Omega-3 fatty acids, video game treatment (e.g., Endeavor Rx), trigeminal nerve stimulation, or biofeedback also have some evidence for the treatment of ADHD.

References

Cortese S, Fava C. Long-term cardiovascular effects of medications for attention-deficit/hyperactivity disorder-Balancing benefits and risks of treatment. JAMA Psychiatry. 2024;81(2):123–24. https://doi.org/10.1001/jamapsychiatry.2023.4126

Dopheide JA, Stutzman DL. Five steps to improve cardiac safety of attention deficit hyperactivity disorder treatment. The Journal of Pediatric Pharmacology and Therapeutics. 2024;29.6:670-673.

Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 2007;46(7):894-921.

Torres-Acosta N, O’Keefe J, O’Keefe C. et al. Cardiovascular effects of ADHD therapies: JACC review topic of the week. JACC. 2020;76(7): 858–866. https://doi.org/10.1016/j.jacc.2020.05.081

Wolraich, Mark L., et al. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019;144(4).

Zhang L, Li L, Andell P, et al. Attention-deficit/hyperactivity disorder medications and long-term risk of cardiovascular diseases. JAMA Psychiatry. 2024;81(2):178–187. doi:10.1001/jamapsychiatry.2023.4294

AUTHOR:

Dr. Kristen Kim, MD

Child, Adolescent and Adult Psychiatrist

Vista Hill Foundation

 Decreased appetite:

If your patient’s appetite decreases because of stimulant medicine, advise the parent to give the morning dose after breakfast so that their child will eat better in the morning. Also advise them to serve a large dinner in the evening when the medication is beginning to wear off. Have them keep healthy, high-calorie, protein snacks on hand for whenever a child asks for food, even if it is before bedtime. Some children do better with two doses (morning and right after lunch) of an immediate-release preparation rather than a long-acting preparation to allow for some food intake at lunch time before the afternoon dose. Discuss with parents that it is more important to monitor the child’s weight rather than his day-to-day appetite. Advise them to let you know if the child’s poor appetite lasts for a long period of time, and consider reducing the dose or stopping the medication on weekends or summer breaks to allow appetite to return to normal.

Stomach pain or upset:

Advise parents not to give the medication on an empty stomach. Taking the medication with or immediately after food can be helpful for this side effect.

Sleep problems:

Parents should set up a regular bedtime routine that includes calming activities, such as bathing or reading.  Make sure that a long-acting stimulant is only given in the mornings, typically no later than 10am, and an afternoon dose of a short-acting stimulant should not be given later than 3pm, sooner if there is sleep disturbance. If the sleep disturbance persists, consider switching from a long-acting to a shorter-acting form or reducing the dose or stopping an afternoon dose. If the child is struggling with hyperactivity at bedtime and having a hard time settling down to sleep because of his ADHD, a non-stimulant medication for ADHD, such as an alpha-agonist) can sometimes be helpful as an adjunctive measure.

Rebounding effects:

When an ADHD medication wears off in the afternoon or evening, some children have more ADHD symptoms or irritability and moodiness.  This is more common with the stimulant medications than the non-stimulant medications. To prevent this “rebounding” consider using a long-acting formulation or prescribing a small dose of short-acting stimulant later in the day. Rebound effects sometimes are a sign that the overall dose of medication is too high. In these cases, it is also important to assess for co-occurring mental health concerns like anxiety and mood issues.

 Mood Changes:

Make sure the parents are keeping an eye out for changes in the child’s mood and anxiety.  Stimulant medications can negatively affect mood symptoms and anxiety in some children. This often improves as the child adjusts to the medication. If that does not occur, consider using a non-stimulant medication as an adjunctive or as a substitute to address the ADHD symptoms.

It is our hope that this article on addressing the common side effects for stimulant medications is helpful to address problems that may arise in the primary care office. Feel free to reach out to us at the SmartCare BHCS Provider Line to discuss specific cases that you might be stuck on.

AUTHOR: Charmi Patel Rao MD, DFAACAP

Co-Medical Director, Vista Hill Foundation

Health Science Clinical Professor, UCSD Department of Psychiatry

President, San Diego Academy of Child and Adolescent Psychiatry

There has been a recent shift in the approach to patients with ID, with greater focus on adaptive functioning across domains, including cognitive, social and practical capacities, rather than based purely on an IQ score. Since ID can be caused by a variety of factors, including genetic, perinatal, environmental and other issues, it is thus important to assess the underlying etiology of the ID, because it can inform the assessment of problems symptoms and guide treatment efforts.

For a patient with Intellectual Disability exhibiting behavioral and emotional symptoms, it is important to conduct a focused medical review of systems as sometimes a patient “acts out” as a way to communicate physical discomfort (for example: from an infection or headache or abdominal issue). Other precipitants may include a behavioral profile to avoid non-preferred activities or as a protest to a change in routine—this particularly with persons who are non-verbal or verbally limited. Individuals with ID are at greater risk of trauma exposure and abuse, so assessment of these potential concerns should also be part of the evaluation protocol.

External considerations aside, co-occurring psychiatric conditions are not uncommon in the population and the most common psychiatric disorders that co-occur are Autism Spectrum Disorders (ASD), Mood Disorders (Anxiety and Depression) and Attention Deficit Hyperactivity Disorder (ADHD). Less frequently, ID patients may also present with co-occurring disorders including psychotic disorders and bipolar conditions which need therapeutic interventions comparable to that given to non-ID individuals.

It is important to ask the patient (if possible) and caregivers about current behavioral and emotional concerns, with attention to how appropriate the symptoms are given the patient’s developmental and functional capacities, and also, how the presenting symptoms are different from their baseline presentation. In this process, it is important to avoid misattributing symptoms to the patient’s ID when they may be a result of a co-morbid psychiatric condition. It can be helpful to use screening tools and use diagnostic criteria adapted for patients with ID conditions.

With respect to patients with co-occurring ID and ADHD, symptoms of hyperactivity tend to occur earlier in the patient’s life and symptoms of inattention tend to last longer into adolescence and young adulthood.   It is of note that stimulant medications, which are the mainstay of treatment for ADHD in youth, are generally less effective in children with co-morbid ID and ADHD. This said, a stimulant trial in patients with co-morbid ADHD symptoms would generally be appropriate along with careful monitoring of side effects and efficacy. Non-stimulants such as the alpha agonists and atypical antipsychotics may be helpful for the young patients with ID and co-morbid disruptive behavioral disorders (including ADHD).

With respect to anxiety and depressive disorders in the ID patient, these individuals may struggle in identifying their feelings, and it can be challenging to assess whether a non-verbal or speech-limited individual’s behaviors is related to underlying anxiety or depression. Input from caregivers across multiple settings can help with this determination. The SSRIs can be useful in patients with ID and clinical depression and/or anxiety, again with close monitoring for side effects.

In summary, when seeing patients with Intellectual Disability, it is important to assess for co-morbid behavioral and emotional concerns and possible psychiatric disorders with full attention to their overall medical and their psychosocial status.

Case Presentation:

10 yo boy with history of motor tic disorder (eye blinking, shoulder shrugging) who was then diagnosed with ADHD combined type. He was started on Concerta and titrated to 36 mg qAM, which has been helpful for his ADHD symptoms but has led to an increase in his motor tics. The question is what to do next?

Discussion:

ADHD is a common issue that presents in the primary care setting. Some children who present with ADHD have co-morbid mental health concerns, including tic disorders, anxiety disorder and depression, which can impact the treatment plan. There are some medications that are used to treat ADHD that can worsen other mental health symptoms, namely tics, anxiety, agitation, and sleep disturbance. Generally, in these situations, the options are to reduce the dose of the medication to see if that helps vs. change to a different medication that does not worsen the other symptoms vs continue the original medication at the current dose and add a second medication to treat the other worsening symptoms.

In the case of co-morbid ADHD and tic disorder, it can be a little bit complicated. There are certainly cases where stimulant medications can worsen tics, but there are also cases where families report an improvement in the tics when the child is started on a stimulant medication or, at the very least, not a worsening of the tics. So if a child has ADHD and one is considering medication treatment, the presence of the tic disorder is not a contraindication to using a stimulant medication, but if one starts with a stimulant medication, it is important to make sure to be monitoring closely for worsening tics. It is helpful to use the lowest possible dose of the stimulant to target the ADHD symptoms effectively, to minimize the risk of worsening the tics. If a medication trial from one class of stimulants causes a worsening in the tics, but a robust response for the ADHD, consider trying a medication from the other class of stimulants next. Alternatively, one could try a non-stimulant medication. The alpha-agonists (guanfacine (Tenex), guanfacine XR (Intuniv), clonidine (Catapres), and clonidine XR (Kapvay)) are good options because they can treat both the ADHD symptoms as well as the tics. Atomoxetine (Strattera) and bupropion (Wellbutrin) are alternative options for ADHD and certainly should not worsen tics, but also would most likely not reduce the tics either. Another option is to use a stimulant as the primary treatment for the ADHD and adjunctive guanfacine or clonidine for the tic disorder.

Case Conclusion:

For this particular case, first, consider reducing the dose of Concerta to see if a lower dose reduces the negative effect on the tics, making sure that the positive effect on his ADHD symptoms continues. If that does not work, consider either changing to a different stimulant (consider Adderall or Vyvanse which are from a different class) or a non-stimulant (consider Tenex or Intuniv which could help with the tic disorder). If the family wants to continue with Concerta because of the positive effect on his ADHD, consider adding adjunctive Tenex to target the tics. Also, the child can also be referred for habit reversal, which is evidence-based cognitive behavioral therapy specifically aimed to reduce tics.

It is our hope that this detailed discussion about a clinical case is helpful for similar situations that might come up in your primary care practices.

Decreased appetite:
If your patient’s appetite decreases after taking ADHD medicine, advise the parent to give the morning dose after breakfast so that the youth will eat better in the morning. Also advise them to serve a large dinner in the evening when the medication is beginning to wear off. Have them keep healthy, high-calorie, protein snacks on hand for whenever a child asks for food, even if it is before bedtime. Discuss with parents that it is more important to monitor the child’s weight than his day-to-day appetite. Advise them to let you know if the child’s poor appetite lasts for a long period, and consider reducing the dose or stopping the drug on weekends or summer breaks to allow appetite and food intake to return to normal.

Stomach pain or upset:
Advise parents not to give the medication on an empty stomach. Taking the medication with or immediately after food can be helpful for this side effect.

Sleep problems:
Parents should set up a regular bedtime routine that includes calming activities, such as bathing or reading.  Makes sure that a long-acting stimulant is only given in the mornings, typically no later than 10am, and an afternoon dose of a short-acting stimulant should typically not be given later than 3pm. If the sleep disturbance persists, the provider could consider switching from a long-acting to a shorter-acting form or reducing the dose or stopping an afternoon dose.

Daytime drowsiness:
If a child is taking atomoxetine (Strattera) or guanfacine (Tenex/Intuniv) or clonidine (Catapres/Kapvay) and experiences daytime sleepiness, consider giving the medication at bedtime instead of in the morning.  The provider could also consider lowering the dose or dividing the dose and giving it twice a day. 

Rebounding effects:
When an ADHD medication wears off in the afternoon or evening, some children have a period of more ADHD symptoms or irritability and moodiness.  This is more common with the stimulant medications than the non-stimulant medications. To prevent this “rebounding” consider using a longer-lasting medication or prescribing a small dose of fast-acting stimulant later in the day.

Mood Changes:
Make sure the parents are keeping an eye out for changes in the child’s mood and anxiety.  Stimulant medications can negatively affect mood symptoms and anxiety. If that does occur, consider using a non-stimulant medication instead to address the ADHD symptoms.

Finally, it is often advisable to schedule medication initiation or dosage changes to occur on weekends when parents can better monitor for side effect emergence

It is our hope that this practical primer on addressing the common side effects for ADHD medications is helpful to address problems that may arise in the primary care office. And remember providers can contact is at SmartCare for real-time consultation on particular cases.

7 year old boy with chief complaint of “frequent meltdowns”. Additional history: daily meltdowns (crying, hitting) with loud sounds or when asked to wear certain clothing; wants to make friends but poor boundaries and accidentally hurts peers at school when he is playing with them; hard time sitting during seat work at school and prefers to move around when doing his work. There is no known language delay or cognitive delay.

It is thought that the prevalence of Sensory Processing Disorder (SPD) is from 5-15% of school-aged children. SPD is commonly misunderstood and either under-diagnosed or misdiagnosed as Autism or Attention Deficit Hyperactivity Disorder (ADHD). While children with Autism commonly have sensory processing difficulties, it is different than for children with SPD.

Sensory processing is how the nervous system manages incoming sensory information and generates responses. Sensory integration is how the body’s eight senses work together to create the body’s responses. The eight senses include:

A child is diagnosed with a SPD when there is difficulty taking in and interpreting sensory information so that an appropriate response can be generated. Here are some indicators that there might be a concern for SPD.

1. Hyper-acute hearing
2. Hypersensitive hearing
3. Touch aversion
4. Poor motor coordination
5. Poor sense of boundaries
6. High pain tolerance
7. Aggression
8. Distractibility
9. Delayed language development
10. Difficulty learning new things

It is not hard to see how these children can be misdiagnosed with Autism or ADHD. Children with Autism also have impairments in communication, social interactions and present with repetitive behaviors and restricted interests, symptoms that are not seen in SPD alone. Children with ADHD present with hyperactivity, impulsivity and inattention without other sensory processing difficulties.

The behavioral symptoms that are seen with SPD (namely aggression, distractibility, difficulty learning new things) occur as a result of the sensory processing difficulties. Sensory input is organized in a manner that enables an individual to establish a sense of where the body is in time and space, to feel safe in one’s own body and to accurately perceive the body’s relationship to the environment. When this doesn’t happen, it can lead to poor arousal regulation. One significant problem is that SPD is not identified as a diagnosis in the DSM, making it difficult to diagnose. Another barrier is that psychiatrists and medical professionals in general are not well trained in diagnosing SPD.

The goal of this e-Weekly article is not to make all of us experts in SPD and other sensory challenges, but to help us to be better aware when the concern might be there and refer for an appropriate evaluation, most likely with an occupational therapist, who are trained to diagnosis SPD and other sensory challenges and make recommendations for the appropriate treatment.