Anxiety

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Anxiety is common and often underdiagnosed
Validated tools should be used to differentiate anxiety from somatic symptoms
In mild to moderate anxiety, lifestyle modification and psychotherapy may be sufficient
Urgent assessment and treatment are needed in patients presenting with suicidality or function loss
There is limited research on the use of pharmacological therapy for anxiety in cirrhosis; consider appropriate dose adjustments

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Assess for anxiety
Consider potential causes
Mild anxiety: consider non-pharmacological therapies
Moderate to severe anxiety: consider pharmacological and non-pharmacological therapies
Reassess using validated tools
References
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Approach to Symptom Assessment

End-of-Life Considerations

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Step 1: Assess for anxiety with validated assessment tools

Anxiety is common and may be pre-morbid, or occur secondary to physiological and psychological changes associated with cirrhosis. Overlapping somatic symptoms (fatigue, insomnia, impaired concentration, irritability) can complicate the diagnosis of anxiety.

Questionnaires are helpful to screen for “at risk” individuals but the diagnosis of anxiety requires a clinical interview

There are a range of screening tools that can be used. The GAD-7 (Generalized Anxiety Disorder) is advantageous because it emphasizes non-somatic symptoms, but other tools such as the HAM-A (Hamilton Anxiety Rating) Scale and Beck Anxiety Inventory can also be used.

GAD-7 (Generalized Anxiety Disorder)

Screening tool which emphasizes non-somatic symptoms

GAD – 7 calculator

It is important to recognize when more urgent assessment is needed

More urgent assessment and possible admission are warranted if patients present with acute suicidality and/or severe functional impairment

Step 2: Consider potential contributing causes

Step 3: Consider Non-pharmacological therapies for treatment of mild anxiety

Step 4: Both pharmacological and non-pharmacological therapies are typically needed for moderate to severe anxiety

If non-pharmacological therapy alone fails, consider adding pharmacological therapy, especially in cases of moderate to severe anxiety. There is limited evidence to guide the use of specific medications in cirrhosis.

Consider benzodiazepines as first-line management only with acute, severe symptoms. These medications are associated with significant adverse effects and are NOT first-line therapy for most patients

Benzodiazepines:

Typically used for severe anxiety symptoms or panic attacks. Avoid sudden benzodiazepine discontinuation in those patients on chronic benzodiazepines
May be used as bridge to long-term anxiety medication/treatment in selected patients
Should ONLY be used short-term (e.g. <2 weeks) to avoid dependence and tolerance
Caution: The use of opioids + benzodiazepines may increase the risk of falls/delirium
Caution: Be very cautious about starting benzodiazepines if there is a history of substance use disorder.
If needed, preferred benzodiazepines to use in liver disease have a short duration in action and are the least likely to cause toxicity = mnemonic ALOT (alprazolam, lorazepam, oxazepam and temazepam)
AVOID clonazepam

Long-term therapy can consist of an SSRI or SNRI (anti-depressant therapy)

Selection of an antidepressant should take into account potential interactions with other medications the patient is prescribed.

SSRIs and SNRIs need dose adjustment of 50% given impaired hepatic metabolism
SSRIs may also increase the risk of bleeding, especially if on an antiplatelet agent
Desvenlafaxine is the only antidepressant that does not undergo significant metabolism by the liver

Choice of medication may be tailored based on symptom patterns

Selection of an antidepressant should take into account potential interactions with other medications the patient is prescribed.

Medication:	Recommended Dose	Additional information
Well-tolerated
Citalopram (SSRI)(immediate release)	10 mg PO daily Max: 20 mg PO daily	GI bleed risk, can lower seizure threshold, risk of QT prolongation, caution with eGFR <20 mL/min.
Mirtazapine	15 mg PO nightly Max: 30 mg PO nightly	Caution with eGFR <30 mL/min (start with 7.5-15 mg, and titrate with close monitoring. Sedating.
Escitalopram (SSRI)	5 mg PO daily Max:10 mg PO daily	GI bleed risk, can lower seizure threshold, risk of QT prolongation, caution with eGFR <20 mL/min.
Sleep disturbance
Sertraline (SSRI)	25 mg PO daily Max:100 mg PO daily	GI bleed risk. NOT recommended in Child Pugh B/C disease.
Mirtazapine	15 mg PO nightly Max: 30 mg PO nightly	Caution with eGFR <30 mL/min (start with 7.5-15 mg, and titrate with close monitoring. Sedating.
Fatigue/Low energy
Fluoxetine (SSRI)	10 mg PO daily Max: 20 mg PO daily	GI bleed risk.
Venlafaxine (SNRI)	37.5 mg PO nightly Max: 112.5 mg PO nightly	GI bleed risk, nausea. NOT recommended in Child Pugh B/C disease.
Desvenlafaxine (SNRI)	50 mg PO daily Max:100 mg PO daily	GI bleed risk, nausea.
Low Appetite/Nausea
Mirtazapine	15 mg PO nightly Max: 30 mg PO nightly	Caution with eGFR <30 mL/min (start with 7.5-15 mg, and titrate with close monitoring. Sedating.
Co-morbid Neuropathic Pain
Venlafaxine (SNRI)	37.5 mg PO nightly Max: 112.5 mg PO nightly	GI bleed risk, nausea. NOT recommended in Child Pugh B/C disease.
Desvenlafaxine (SNRI)	50 mg PO daily Max:100 mg PO daily	GI bleed risk, nausea.

Ensure the patient’s symptoms are reassessed, using validated tools

This section was adapted from content using the following evidence based resources in combination with expert consensus. The presented information is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient’s care.

Authors (Alphabetical): Amanda Brisebois, Sarah Burton-Macleod, Ingrid DeKock , Martin Labrie, Noush Mirhosseini, Nicholas Mitchell, Mino Mitri, Kinjal Patel, Aynharan Sinnarajah, Puneeta Tandon, Sarah Tymchuk

Thank you to pharmacists Omer Ghutmy and Meghan Mior for their help with reviewing these pages.

Helpful Links:

Self-test for anxiety (GAD-7): https://myhealth.alberta.ca/health/pages/conditions.aspx?Hwid=abn2339
Alberta Health Services Self-Help tips: https://www.albertahealthservices.ca/news/page13125.aspx

References:

Davison SN on behalf of the Kidney Supportive Care Research Group. Conservative Kidney Management Pathway; Available from: https//:www.CKMcare.com.
Medication prescribing in liver dysfunction. Ment Health Clin [Internet]. 2014;4(3):131-7, doi: https://doi.org/10.9740/mhc.n197913
Mullish BH, Kabir MS, Thursz MR, Dhar A. Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther. 2014 Oct;40(8):880-92. doi: 10.1111/apt.12925. Epub 2014 Sep 1. PMID: 25175904.
Telles-Correia D, Barbosa A, Cortez-Pinto H, Campos C, Rocha NB, Machado S. Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity. World J Gastrointest Pharmacol Ther. 2017 Feb 6;8(1):26-38. doi: 10.4292/wjgpt.v8.i1.26. PMID: 28217372; PMCID: PMC5292604.
Wilcock A, Charlesworth S, Prentice W, Selby P, McKenna M, Cripps S, Considine A, Orr A, Wright M, Mihalyo M, Oxberry S. Prescribing in Chronic Severe Hepatic Impairment. J Pain Symptom Manage. 2019 Sep;58(3):515-537. doi: 10.1016/j.jpainsymman.2019.04.034. Epub 2019 May 9. PMID: 31077785.

Anxiety

Top tips:

Navigation

Knowing your
Patient

Approach to Symptom Assessment

Symptom Management Principles

Drug Dosing
in Cirrhosis

End-of-Life Considerations

Helpful Links:

References:

We gratefully acknowledge the Physician Learning Program for their design assistance.

We would really appreciate your feedback to make this page better. Thanks for taking the time to do this!

We would really appreciate your feedback to make this page better. Thanks for taking the time to do this!

Anxiety

Top tips:

Navigation

Knowing your Patient

Approach to Symptom Assessment

Symptom Management Principles

Drug Dosing in Cirrhosis

End-of-Life Considerations

Helpful Links:

References:

We gratefully acknowledge the Physician Learning Program for their design assistance.

We would really appreciate your feedback to make this page better. Thanks for taking the time to do this!

We would really appreciate your feedback to make this page better. Thanks for taking the time to do this!

Knowing your
Patient

Drug Dosing
in Cirrhosis