Can Immunotherapy Cause Depression Symptoms and How to Cope

Immunotherapy can be linked to mood changes, including depression, in some people, though it doesn’t happen to everyone. These changes may arise directly from immune effects on the brain, from treatment‑related hormone (endocrine) problems, or from the stress and fatigue of cancer care. ^[1] Mood changes such as irritability, decreased interest, forgetfulness, and behavior changes are recognized in the context of immunotherapy side effects and should be promptly discussed with the care team. ^[1] Immune activation and certain cytokines have long been associated with depressive symptoms like fatigue, sleep disturbance, and low mood, and antidepressant treatment can help in some cases. [PM9]

Why depression can occur

• Immune effects on the brain: Pro‑inflammatory signals (cytokines) released during cancer and immunotherapy can alter neurotransmitters and stress hormones, contributing to low mood, anxiety, and fatigue. [PM9] These brain‑immune interactions can sensitize stress responses over time, increasing vulnerability to depression. [PM9]
• Endocrine (hormone) side effects: Immunotherapy can inflame glands like the thyroid, pituitary, and adrenal, leading to conditions such as hypothyroidism, hypophysitis, or adrenal insufficiency that often cause fatigue, slowed thinking, and depressed mood. ^[1] Recognizing and treating these hormone issues is essential because mood can improve once the endocrine problem is fixed. ^[2]
• Rare neuroinflammation: Very rarely, immunotherapy can be associated with brain inflammation (encephalitis) that presents with confusion, memory problems, hallucinations, or severe psychiatric symptoms; this requires urgent medical evaluation. ^[3] Headache, fever, and new confusion in this setting are red flags for immediate care. ^[3]

Common warning signs to watch

• Persistent sadness or hopelessness, loss of interest, irritability, or decreased motivation. ^[1]
• Severe fatigue, sleep changes, appetite changes, trouble concentrating, or forgetfulness. ^[1]
• Any thoughts of self‑harm or suicide, new confusion, or hallucinations seek urgent help. ^[3]

How to cope and manage safely

• Tell your oncology team early: Report mood or behavior changes, even mild ones; early action can prevent worsening and allows dose/schedule adjustments when appropriate. ^[4] Your team may check thyroid, pituitary, and adrenal function and treat endocrine causes that often relieve depressive symptoms. ^{[1] [2]}
• Screen and treat depression: Routine distress screening is recommended during cancer care, and treatment counseling, cognitive strategies, and when needed, medications can reduce symptoms and improve quality of life. ^[5] Evidence‑based cognitive techniques help with scan‑related anxiety and ongoing worries during immunotherapy. ^[6]
• Medications when appropriate: Antidepressants can be considered and may attenuate cytokine‑related depressive symptoms; clinicians will choose agents that are safe with your cancer treatments. [PM9] Close collaboration between oncology and mental health providers helps tailor therapy and monitor for interactions. ^[5]
• Address fatigue and daily routines: Pace activities, prioritize rest, gentle exercise as tolerated, and balanced nutrition; fatigue management reduces overall symptom burden during immunotherapy. ^[7] Building predictable sleep and activity routines can support mood stabilization during treatment. ^[7]
• Know urgent red flags: Sudden severe headache, fever, confusion, or new psychotic symptoms need rapid assessment because they can signal rare but serious neuroinflammation. ^[3] Marked lethargy, dizziness, or low blood pressure with mood changes may indicate an acute endocrine crisis that needs immediate care. ^[2]

When treatment changes are needed

If mood symptoms are significant, your clinicians may temporarily pause immunotherapy, investigate reversible causes, and resume once stabilized, aligning with standard immune‑related adverse event management principles. ^[2] Adjusting care plans and adding supportive strategies can help maintain safety while continuing effective cancer treatment. ^[4]

Bottom line

• Depression can occur during immunotherapy, often through immune and endocrine pathways, but it is treatable. ^[1] [PM9]
• Early reporting, endocrine evaluation, evidence‑based counseling, and appropriate medications form the core of safe management. ^{[1] [5]}
• Seek urgent help for red‑flag neurological or severe endocrine symptoms to prevent complications. ^{[3] [2]}