Anxiety in cancer patients: reactive or organic?

A woman undergoing breast cancer treatment arrives at the outpatient clinic saying she can no longer sleep. She feels her heart racing, her hands tremble, and some days she wakes up with the feeling that something terrible is going to happen. Her family says she is "very nervous about the illness," and the explanation seems obvious. She received a difficult diagnosis, is in the middle of chemotherapy, and is afraid of the future.

The explanation may be right. But before accepting that anxiety is just a reaction to cancer, the clinician must ask a question that changes management: is there any organic or medication cause producing these symptoms? In oncology, this question has many possible answers. Corticosteroids, hormonal, metabolic and neurological disorders, effects of other medications, and poorly controlled physical symptoms can present as anxiety.

This text organizes that reasoning. It discusses what is expected after the diagnosis, how to screen without labeling, which organic causes mimic anxiety, which medications cause it, and how to separate anxiety from symptoms such as shortness of breath and pain.

Key points

• Between 12 and 25 out of every 100 people with cancer have anxiety symptoms on questionnaires (Grassi, 2023).
• Corticosteroids can cause insomnia, anxiety and irritability, usually in the first weeks (Seymour, 2025).
• Immunotherapy-induced thyroiditis, hypoglycemia, hypercalcemia and secretory tumors can mimic anxiety.
• Antiemetic-induced akathisia is often mistaken for anxious agitation (Vanegas-Arroyave, 2024).
• Short instruments such as GAD-2 and GAD-7 help screen but do not diagnose the cause.
• Labeling as reactive before investigating can delay a treatable diagnosis.

Summary

• Why this is a reasoning scenario
• Expected anxiety, disorder and screening
• Organic causes that mimic anxiety
• Medications that produce anxiety
• Physical symptoms that are confused with anxiety
• Building the reasoning step by step
• How NEXO helps train this reasoning
• Frequently asked questions
• Take-home messages

Why this is a reasoning scenario

Anxiety is one of the most common symptoms in oncology and one of the easiest to explain. Almost everyone understands why someone with cancer would be anxious, and this understanding, which is human and necessary, creates a risk for clinical reasoning. When the psychological explanation seems sufficient, the investigation stops.

This early closure is one of the best-known errors in diagnosis. The clinician finds a plausible explanation, feels they have understood the problem, and stops looking for alternatives. In a person with cancer, the alternatives are many, and some are serious: metabolic disorders, medication effects, inflammation of the nervous system, and hormonal changes caused by the treatment itself.

A case report of pheochromocytoma shows how far this error can go. The patient spent 13 years in psychiatric treatment for anxiety before the catecholamine-secreting tumor was identified (Alguire, 2018). The story is rare, but it teaches a general rule: a symptom that seems psychological can have a physical cause, and the physical cause only appears when it is sought.

Reactive and organic anxiety can also coexist. The same person may be afraid of the diagnosis and, at the same time, have thyroiditis or hypoglycemia. Therefore, the goal is not to choose between one explanation and another, but to ensure that no treatable cause is left out.

The reasoning can be organized into three questions. The first is what is expected after the diagnosis, and what already constitutes a disorder. The second is whether there is an organic or medication cause that explains the symptoms. The third is whether another physical symptom, such as shortness of breath or pain, is being described as anxiety. The following sections go through these questions in the order they usually appear in the office.

The order matters because each question changes what comes next. Those who answer only the first tend to treat the fear and reassess weeks later. Those who go through all three, even quickly, can order in the same visit the few tests that separate the expected from the treatable.

Expected anxiety, disorder and screening

Feeling afraid after a cancer diagnosis is expected. The European guideline on anxiety and depression in adults with cancer describes that between 12 and 25 out of every 100 patients have anxiety symptoms on screening questionnaires (Grassi, 2023). Anxiety disorders defined by interview are less frequent, close to 10 out of every 100 in a meta-analysis of 10 071 patients (Grassi, 2023).

The difference between the two numbers matters. Many patients have symptoms that fluctuate, appear near scans or results appointments and improve with information, support and time. A smaller group develops a persistent picture that interferes with sleep, work, relationships and the ability to continue treatment.

The guideline recommends screening for anxiety and depression at key points in care, such as diagnosis, treatment, end of treatment and recurrence (Grassi, 2023). The same guideline notes that screening is only the first step, and that those who score positive should receive a more formal assessment (Grassi, 2023). This assessment includes looking for organic causes.

Short instruments

The GAD-7 is one of the most used questionnaires. A study evaluated the instrument in 718 people aged 70 or older with advanced cancer and found good psychometric properties in this population (Saracino, 2024). The two-item version, the GAD-2, had an area under the curve between 0.93 and 0.96 relative to the full GAD-7 (Saracino, 2024).

Two-step screening uses a short symptom scale first and the full questionnaire only for those who score positive. A study of 172 oncology patients tested this strategy with real-world data, using the GAD-7 as the second step for anxiety (Gascon, 2024). In this sample, 39 of the 172 patients were diagnosed with an anxiety disorder at interview (Gascon, 2024).

The instruments measure symptom intensity, but they do not say where the symptoms come from. A high GAD-7 in a person with immunotherapy-induced thyroiditis stays high, and the right treatment is the one for the thyroid. The questionnaire opens the conversation; the history, the examination and a few laboratory tests complete the reasoning.

When anxiety calls for another explanation

Some signs suggest that a reactive explanation may not be enough:

• sudden onset, with no clear relation to an event of the disease;
• intense physical symptoms, such as tachycardia, tremor and sweating, out of proportion to the fear reported;
• onset soon after a new medication or a change in treatment;
• confusion, drowsiness, change in memory or behavior;
• episodes while fasting or that improve after eating;
• no previous history of anxiety and little response to the usual measures.

Each of these signs, on its own, is far from proving an organic cause, but it raises the chance that one exists. When they appear, the next step is to review the medication list and order targeted tests.

Organic causes that mimic anxiety

Several conditions common in oncology produce symptoms that the patient describes as nervousness, chest tightness or fear without reason. They vary according to the tumor and the treatment, but some deserve to be remembered in almost every case.

Immunotherapy-induced thyroiditis

Immune checkpoint inhibitors can inflame the thyroid. The review on thyroid adverse events describes that thyroiditis usually appears in the first 3 months of treatment, often with an initial phase of thyrotoxicosis (Muir, 2022). In this phase, palpitations, tremor, insomnia and a feeling of restlessness are frequent and can be read as anxiety.

The phase of excess hormone is usually transient, and more than 40 out of every 100 patients with thyroiditis progress to hypothyroidism (Muir, 2022). The review notes that most cases are asymptomatic and found by monitoring thyroid function, recommended at the start and repeated every 6 weeks after treatment begins (Muir, 2022). When there are symptoms, however, measuring TSH and free T4 is a simple test that deserves to be ordered in the face of new anxiety in someone receiving immunotherapy. The text on what to watch for during immunotherapy discusses other immune-mediated events.

Hypoglycemia

Hypoglycemia produces adrenergic symptoms that closely resemble an anxiety attack: sweating, tremor, palpitations and hunger. In oncology, it can be caused by tumors that produce insulin-like factors, a situation described in the review on paraneoplastic hypoglycemia (Karamanolis, 2024). The review recalls Whipple's triad: compatible symptoms, a low glucose measured at the time and improvement with correction (Karamanolis, 2024).

The review describes tumors of epithelial, vascular and mesenchymal origin associated with this picture, with mesotheliomas and fibrosarcomas among the most cited mesenchymal ones (Karamanolis, 2024). In someone with a large tumor and unexplained episodes of malaise, blood glucose deserves to be remembered.

Episodes that appear on fasting, at dawn or after exercise are a clue. Measuring blood glucose during the episode is the most direct way to confirm or rule out the hypothesis. The text on how hypoglycemia presents describes the symptoms in detail.

Hypercalcemia

Hypercalcemia is one of the most common metabolic complications of cancer. The review on malignant hypercalcemia includes anxiety among the neurological manifestations, alongside depression, fatigue, lethargy, weakness and confusion, more marked at moderate and severe levels (Feldenzer, 2018). When anxiety comes together with thirst, nausea and constipation, calcium becomes a mandatory test.

Calcium measurement, corrected by albumin or ionized, is quick and changes management. People with bone metastases, myeloma or tumors that produce parathyroid hormone-like substances are among those at highest risk (Feldenzer, 2018).

Secretory tumors

Pheochromocytoma and paraganglioma produce catecholamines and can cause episodes of palpitation, sweating, headache and a feeling of panic. The report of 13 years of anxiety treated as a psychiatric disorder shows how this picture can go unnoticed (Alguire, 2018). The investigation starts with metanephrines, as discussed in the text on what an adrenal nodule can produce.

Limbic encephalitis and brain tumors

Limbic encephalitis, which can be paraneoplastic, manifests with anxiety, mood changes, seizures and loss of recent memory. The review on neuropsychiatric disorders from limbic encephalitis describes the Graus criteria for diagnosis, which combine the clinical picture with MRI, electroencephalogram and cerebrospinal fluid (Kao, 2020).

The same review describes that the picture usually begins acutely or subacutely, with memory deficit and confusion at its core, and that psychiatric symptoms such as anxiety, depression or psychosis can appear together with changes in behavior and sleep (Kao, 2020). New anxiety with recent forgetfulness, a seizure or a change in behavior is reason to consider this hypothesis.

Brain tumors also change mood directly. In the review on depression and anxiety in people with glioma, anxiety appears in 24 to 48 out of every 100 patients, according to the study (van der Meer, 2023). In these cases, tumor location, edema and epileptic seizures enter the explanation, alongside the reaction to the diagnosis.

Medications that produce anxiety

Reviewing the list of medications is one of the most productive steps when facing new anxiety in a cancer patient. Several routinely used medications can cause or worsen the symptoms, and the timing is usually the main clue.

Corticosteroids

Corticosteroids are among the most used medications in oncology, as antiemetics, for brain edema, pain and appetite. A 10-year series identified 297 patients with mental disorders induced by corticosteroids, equivalent to 11 out of every 100 of 2626 referrals to the oncology psychiatry service (Seymour, 2025). Dexamethasone was the most involved corticosteroid, and symptom onset had a median of 14 days (Seymour, 2025).

Insomnia, anxiety and irritability were the most common symptoms in the series, which also described mood and psychosis presentations (Seymour, 2025). The authors describe a spectrum ranging from mild changes in mood and sleep to suicidal ideation and frank psychosis, and breast cancer was the most frequent tumor among the women in the series (Seymour, 2025). In most patients, the team started some psychotropic drug, which shows that the condition rarely resolves with reassurance alone (Seymour, 2025). Asking when the corticosteroid started, whether the regimen changed and whether the person takes the medication at night helps link the symptom to the cause.

Withdrawal from the corticosteroid can also produce symptoms. Fatigue, malaise, pain and mood changes can appear when the medication is reduced, and some people describe this period as a phase of nervousness. The medication history, with dates, is as important as the current list.

Akathisia

Akathisia is a motor restlessness with an intense urge to move, which leads the person to pace back and forth and to be unable to sit still. The update on medication-induced movement disorders describes akathisia as an effect of dopamine-blocking agents, including antiemetics such as metoclopramide (Vanegas-Arroyave, 2024).

The patient usually describes akathisia as anxiety, and the team may interpret the agitation as emotional worsening. The review also points out that anticholinergics are not recommended to treat akathisia, which reinforces the importance of recognizing the condition and reviewing the causative medication (Vanegas-Arroyave, 2024).

Anticonvulsants

In people with brain tumors, anticonvulsants can alter mood. The review on glioma reports that, in a study with levetiracetam, 69 of 429 patients discontinued the medication due to adverse effects, and 7 of them due to depression (van der Meer, 2023). Irritability and anxiety also appear among the described effects.

Other medications to remember

The list can be reviewed with a few simple questions:

• has any corticosteroid been started, increased or reduced recently;
• has any dopamine-blocking antiemetic been introduced;
• did immunotherapy start in the last few months;
• is there an anticonvulsant, bronchodilator or stimulant in use;
• has any sleep or anxiety medication been stopped suddenly;
• does the patient use alcohol, nicotine or other substances and has the consumption changed.

Physical symptoms that are mistaken for anxiety

Some physical complaints are described by the patient with emotional words. Shortness of breath, poorly controlled pain, nausea and insomnia can generate fear and restlessness, and the right treatment is the one for the underlying symptom.

Dyspnea

Shortness of breath and anxiety feed each other. The person who feels short of breath becomes afraid, and fear worsens the sensation of shortness of breath. A meta-analysis on benzodiazepines for dyspnea in patients with cancer compared midazolam with morphine and found a relative risk of 0.95, with no clear difference between the two (Yasuda, 2023).

The authors concluded that the benzodiazepine alone did not significantly improve dyspnea compared with opioids and that the combination may help in selected cases (Yasuda, 2023). For clinical reasoning, the lesson is different: when anxiety appears together with shortness of breath, the cause of the dyspnea, such as pleural effusion, anemia, embolism or tumor progression, must be sought before treating only the fear.

Pain and other symptoms

Poorly controlled pain causes insomnia, irritability and a feeling of constant threat. Persistent nausea, constipation and urinary retention can also manifest as restlessness, especially in older adults and in those who have difficulty communicating. In hospitalized people, agitation can be a sign of delirium, and the text on how to look for the cause of delirium shows the investigation.

When anxiety is the right response

After ruling out organic causes, reactive anxiety deserves its own care. Clear information, time for questions, psychological support and, when indicated, pharmacological treatment are part of oncology care. The European guideline describes psychotherapy, cognitive behavioral therapy and mindfulness-based therapies as effective treatments (Grassi, 2023).

Anxiety also affects the patient's own reasoning about the disease, which the text on how anxiety affects reasoning discusses in another context.

Building the reasoning step by step

Returning to the patient from the opening, the reasoning starts with questions about timing and treatment. When did the symptoms begin? What changed in the medication in the previous weeks? Is she receiving a corticosteroid along with chemotherapy? Does she use an antiemetic? Has she started immunotherapy? Are the episodes related to fasting or to the time of day?

The physical examination looks for signs that the emotional complaint hides: persistent tachycardia, fine tremor, goiter, weight loss, motor restlessness, dehydration and neurological changes. Initial tests are usually simple, and the list should be adapted to the tumor and the treatment.

The European guideline only accepts the diagnosis of anxiety disorder when the picture is not explained by a medication or a clinical disease (Grassi, 2023). The table summarizes the main clues, without a fixed order: the history decides where to start, and each row gives the source for the first step.

Clue	Hypothesis	First step
Onset weeks after corticosteroid	Corticosteroid effect	Review regimen and timing (Seymour, 2025)
Motor restlessness after antiemetic	Akathisia	Review the dopamine blocker (Vanegas-Arroyave, 2024)
Palpitations and tremor with immunotherapy	Thyroiditis	TSH and free T4 (Muir, 2022)
Episodes on fasting, sweating and hunger	Hypoglycemia	Blood glucose during the episode (Karamanolis, 2024)
Confusion, thirst and constipation	Hypercalcemia	Corrected or ionized calcium (Feldenzer, 2018)
Episodes of palpitations and headache	Secretory tumor	Metanephrines (Alguire, 2018)
Memory change or episodes	Encephalitis or brain lesion	Imaging and neurological assessment (Kao, 2020)
Shortness of breath with fear	Dyspnea with its own cause	Look for the cause of the dyspnea (Yasuda, 2023)

If the patient started dexamethasone with chemotherapy and the symptoms appeared two weeks later, the corticosteroid becomes the main hypothesis, as the median described in the case series suggests (Seymour, 2025). If she is receiving immunotherapy, TSH measurement comes before any label. If the tests are normal and the history points to fear of the diagnosis, reactive anxiety becomes the most likely explanation, now based on an investigation and not on an assumption.

The diagnosis of reactive anxiety is legitimate and common. The difference is that it should be a conclusion, not a starting point. The text on what anxiety is helps review the basic concepts.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by looking for the code in ICD-10.

The limits on using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information under Curator and Creators, and institutions can learn about the proposal on the partnerships page. Training differential diagnosis with clues and looking for the right code in ICD-10 complete this practice.

Frequently asked questions

Is anxiety common in people with cancer?

Yes. Between 12 and 25 out of every 100 patients have anxiety symptoms on screening questionnaires, and about 10 out of every 100 have an anxiety disorder (Grassi, 2023).

Can a corticosteroid cause anxiety?

It can. In a series of 297 patients with mental disorders induced by corticosteroids, insomnia, anxiety and irritability were the most common symptoms, with onset at a median of 14 days (Seymour, 2025).

Which tests help rule out an organic cause?

They depend on the context. TSH and free T4 in those receiving immunotherapy, blood glucose during episodes, calcium and, when a secretory tumor is suspected, metanephrines (Muir, 2022).

What is akathisia?

It is a motor restlessness with an urge to move, caused by drugs that block dopamine, such as some antiemetics, and often mistaken for anxiety (Vanegas-Arroyave, 2024).

Is GAD-7 suitable for older oncology patients?

It works. In 718 people aged 70 or older with advanced cancer, the instrument had good psychometric properties (Saracino, 2024).

Does a benzodiazepine resolve anxious shortness of breath?

The data show that, on its own, it did not significantly improve dyspnea compared with opioids, and the combination may help in selected cases (Yasuda, 2023).

Take-home messages

• Anxiety is common in cancer, but the reactive explanation should be a conclusion, not a starting point.
• Corticosteroids, antiemetics and anticonvulsants are among the medications that most often produce anxiety symptoms.
• Immunotherapy-induced thyroiditis, hypoglycemia, hypercalcemia and secreting tumors can present as anxiety.
• Short questionnaires screen well, but the cause depends on the history, the examination and targeted tests.
• Shortness of breath and pain can be described as anxiety and call for treatment of the cause.
• Reactive and organic anxiety can coexist in the same person.

Want to practice the differential diagnosis of symptoms that seem emotional? Play the case of the day on NEXO.

References

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2. Feldenzer KL, Sarno J. Hypercalcemia of Malignancy. J Adv Pract Oncol. 2018. PMID 31086686.
3. Gascon B, Elman J, Macedo A, et al. Two-Step Screening for Depression and Anxiety in Patients with Cancer: A Retrospective Validation Study Using Real-World Data. Curr Oncol. 2024. PMID 39590112. DOI 10.3390/curroncol31110481.
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5. Kao YC, Lin MI, Weng WC, et al. Neuropsychiatric Disorders Due to Limbic Encephalitis: Immunologic Aspect. Int J Mol Sci. 2020. PMID 33396564. DOI 10.3390/ijms22010389.
6. Karamanolis NN, Kounatidis D, Vallianou NG, et al. Paraneoplastic hypoglycemia: An overview for optimal clinical guidance. Metabol Open. 2024. PMID 39185033. DOI 10.1016/j.metop.2024.100305.
7. Muir CA, Tsang VHM, Menzies AM, et al. Immune Related Adverse Events of the Thyroid: A Narrative Review. Front Endocrinol (Lausanne). 2022. PMID 35692394. DOI 10.3389/fendo.2022.886930.
8. Saracino RM, Kehoe LA, Sohn MB, et al. Psychometric Properties of the Generalized Anxiety Disorder Scale (GAD-7) in Older Adults With Advanced Cancer. Psychooncology. 2024. PMID 39482282. DOI 10.1002/pon.70012.
9. Seymour N, Ismail MF, Doherty K, et al. Steroid-Induced Mental Disorders in Oncology Patients: A 10-Year Retrospective Case Series Review. Psychooncology. 2025. PMID 40252049. DOI 10.1002/pon.70137.
10. van der Meer PB, Dirven L, Hertler C, et al. Depression and anxiety in glioma patients. Neurooncol Pract. 2023. PMID 37457222. DOI 10.1093/nop/npad019.
11. Vanegas-Arroyave N, Caroff SN, Citrome L, et al. An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders. CNS Drugs. 2024. PMID 38502289. DOI 10.1007/s40263-024-01078-z.
12. Yasuda S, Sugano K, Matsuda Y, et al. Systematic review and meta-analysis of the efficacy of benzodiazepines for dyspnea in patients with cancer. Jpn J Clin Oncol. 2023. PMID 36636762. DOI 10.1093/jjco/hyac206.