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CAM scale

Epworth Sleepiness Scale

Sleep Timing and Sleep Quality Screening Questionnaire

ESAS-r Pain Scale

PEG 3-Item Scale (Pain, Enjoyment and General Activity scale)

GAD – 7 Scale

Anxiety

Top tips:

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

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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
Potential contributing factors include
  • Biological: Encephalopathy, uremia, pain, dyspnea, ascites, poor nutrition, impaired sleep, substance use history, medication side effects and medical co-morbidities
  • Psychological: Difficulties coping with chronic disease, inability to engage in prior activities, limited coping skills, past trauma and psychiatric co-morbidities
  • Social: Loss of employment, financial stressors, housing insecurity, change in social role (e.g. informal caregiving) or work, change in or loss of romantic and interpersonal relationships, social isolation, cultural factors
Step 3: Consider Non-pharmacological therapies for treatment of mild anxiety

Consider non-pharmacological management in all patients with mild anxiety.

These therapeutic techniques can be learned using online resources (apps) or text resources in situations where access to a therapist is difficult.

Lifestyle modification
Psychotherapy with CBT and MBSR

Cognitive Behavioral Therapy (CBT) and Mindfulness Based Stress Reduction (MBSR) are both effective for the management of anxiety in chronic illness.

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

Once initiated, treatment should be re-assessed at 2 weeks using validated questionnaires (e.g. GAD-7) to evaluate response.

  • If there is improvement at two weeks, consider increasing the dose to further target symptoms
  • If there is no improvement or significant side effects at follow-up, the likelihood of symptom remission is low. An alternate medication trial should be considered
  • A full trial of an antidepressant (used for anxiety) occurs when the maximum allowable dose is used for 8 weeks.

 

Consider referral to psychiatrist or mental health specialist
  • Lack of response to an adequate trial of TWO anti-depressants (used for anxiety)
  • Severe symptoms or functional impairment

 

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: 
  1. Self-test for anxiety (GAD-7): https://myhealth.alberta.ca/health/pages/conditions.aspx?Hwid=abn2339
  2. Exercise Therapy: http://cirrhosiscare.ca/healthy-living-provider/exercise-therapy-hcp/ 
  3. Nutrition Therapy: http://cirrhosiscare.ca/healthy-living-provider/nutrition-therapy-hcp/
  4. Alberta Health Services Self-Help tips: https://www.albertahealthservices.ca/news/page13125.aspx
References:
  1. Davison SN on behalf of the Kidney Supportive Care Research Group. Conservative Kidney Management Pathway; Available from: https//:www.CKMcare.com.
  2. Medication prescribing in liver dysfunction. Ment Health Clin [Internet]. 2014;4(3):131-7, doi: https://doi.org/10.9740/mhc.n197913
  3. 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.
  4. 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.
  5. 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.
We gratefully acknowledge the Physician Learning Program for their design assistance.

PHQ-9 Depression Scale