SSRI Antidepressant Fluoxetine Improving Immunotherapy Efficacy in Advanced Hepatobiliary Malignancy Patients With Depression and Anxiety

Inclusion Criteria:

* Age: 18 to 80 years old, both male and female are acceptable.
* The histopathological/cytological diagnosis is hepatocellular carcinoma or cholangiocarcinoma. Hepatocellular carcinoma can be diagnosed by imaging.
* Patients with metastatic advanced or locally advanced liver and gallbladder malignancies;
* No treatment has been received and a first-line treatment regimen including PD-1 inhibitors /PD-L1 inhibitors is planned to be carried out;
* Patients with a PHQ-9 score of ≥10 or a GAD-7 score of ≥8, that is, those with positive screening for depression or anxiety;
* At least one lesion measurable by CT or MRI (with a maximum diameter of ≥0.5cm);
* ECOG: 0-2;
* Child-Pugh score ≤7 points;
* The expected survival period is ≥12 weeks.
* Baseline blood cell count tests and blood biochemistry must meet the following standards:1) White blood cell count ≥3.0×10\^9/L; Hemoglobin ≥90 g/L;2) Absolute neutrophil count ≥1.5×10\^9/L;3) Platelet count ≥100×10\^9/L;4) Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of the normal upper limit (ULN);5) Total bilirubin ≤ twice ULN;6) Serum creatinine ≤ 1.5 times ULN; Albumin ≥30 g/L;
* The subjects voluntarily joined this study, signed the informed consent form, had good compliance and cooperated with the follow-up.

Exclusion Criteria:

* Those with uncorrectable coagulation dysfunction and a distinct bleeding tendency;
* Patients who currently have unstable or active ulcers or gastrointestinal bleeding;
* Severe functional insufficiency of vital organs, such as severe cardiopulmonary insufficiency, etc;
* Patients with hepatic encephalopathy or intractable ascites requiring treatment;
* A history of mental disorders such as bipolar disorder, schizophrenia, and active suicidal ideation;
* Patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (active is defined as a viral load \> 20,000 IU/mL), or those who are positive for HBV or HCV and refuse to receive standardized antiviral treatment;
* Unable to swallow oral medication;
* Patients allergic to fluoxetine;
* Currently using drugs that may have serious interactions with fluoxetine;
* The researchers assessed that the patient was unable or unwilling to comply with the requirements of the research protocol.