Enclara Pharmacia Presents Depression Management Study

Share +

NW is an 80-year-old female admitted to hospice yesterday with a primary diagnosis of congestive heart failure. Her co-morbidities include hypertension and coronary artery disease. She has allergies to penicillin, which caused a rash, and lorazepam with reported confusion. She was recently started on duloxetine by her family doctor to manage constant worry, irritability, and sadness. NW lives with her daughter who also reports that her mother has trouble sleeping due to these recent symptoms.

Current medications include:

  • Amlodipine (Norvasc®) 5mg; 1 tab po daily for blood pressure
  • Carvedilol (Coreg®) 3.125mg; 1 tab po BID for heart failure
  • Clopidogrel (Plavix®) 75mg; 1 tab po daily for clot prevention
  • Digoxin (Lanoxin®) 0.125mg; 1 tab po daily for heart failure
  • Duloxetine (Cymbalta®) 30mg; 1 cap po daily for mood
  • Furosemide (Lasix®) 40mg; 1 tab po BID for fluid retention
  • Morphine (Roxanol®) 20mg/ml; 25ml po/sl every 3 hours PRN pain or shortness of breath
  • Spironolactone (Aldactone®) 25mg; 1 tab po daily for fluid retention
  • Albuterol (Ventolin®) inhaler; Inhale 2 puffs po q4h PRN shortness of breath

NW’s blood pressure is currently controlled and lower extremity edema that has been a problem in the past is being managed well with her diuretics. Her family reports that she frequently gets up to use the bathroom at night. She experiences shortness of breath with activity and uses an albuterol inhaler as needed. She uses morphine 1-2 times per day for pain with good response. She has a history of becoming confused with lorazepam, however, her family states that she has tolerated other benzodiazepines in the past. The duloxetine that was started two weeks ago by her family doctor has already improved NW’s mood, however, she continues to have problems sleeping.   Duloxetine is not on the hospice pharmacy’s formulary, but the formulary includes a number of SSRIs.

What are symptoms of depression at end-of-life?

 Depression is a medical illness that involves both the mind and body. Hospice patients may face a greater likelihood of developing or worsening a clinical diagnosis of depression due to the awareness of their limited lifespan. Common symptoms include feelings of sadness/unhappiness, irritability, loss of interest/pleasure in normal activities, insomnia or excessive sleeping, changes in appetite or an increased craving for food, and agitation.  Other symptoms include slowed thinking or body movements (psychomotor slowing), decreased concentration, fatigue, loss of energy, feelings of worthlessness or guilt, frequent thoughts of death, crying spells and unexplained physical problems.  Due to its symptoms, depression has a negative impact on quality of life and untreated depression leads to significant morbidity and mortality also negatively affects caregivers.  In some people, depression is also associated with an increased desire for hastened death.

What must be assessed before initiating an antidepressant?

 Before initiating drug therapy, it is important to rule out other factors such as medications or comorbidities that may be causing or worsening depression.  Review the medication list and try to relate changes in medication to the onset of the symptoms and rule out other secondary causes such as:

  • Co-morbidities: Anemia, cancer, cardiac disease, endocrine disorders, infections, metabolic disorders, neurological disorders
  • Medications: Baclofen, barbiturates, benzodiazepines, beta-blockers, clonidine, corticosteroids, diuretics, opioids
  • Other: Alcoholism, psychosocial issues, pain, insomnia

Evaluate patient with DSM-IV criteria or utilize another depression screening assessment tool or simply ask the patient, “Are you depressed?” Consider the following as a part of a differential diagnosis and recognize that prognosis will affect treatment approaches:1

  • Major depressive disorder: Treat with drug therapy plus psychotherapy
  • Unspecified depressive disorder: Continually assess; May treat with drug therapy plus psychotherapy
  • Adjustment disorder with depressed mood: Treat with supportive counseling aimed at coping skills and problem solving aimed at resolving or removing stressor
  • Grief: Treat with supportive counseling or psychotherapy
  • Demoralization: Treat with supportive counseling or psychotherapy

How do I choose the right antidepressant?1-3

Depression may be mediated by the depletion of several neurotransmitters including norepinephrine, serotonin, and dopamine. Antidepressants affect how these neurotransmitters behave, but how they improve symptoms is not well understood. All antidepressants have similar efficacy, so chose an agent based on patient history and comorbidities, prognosis, side effects and tolerability, potential drug interactions and cost. All agents provide some symptom improvement in the initial weeks of therapy, however, it may take 1-2 months of dose titration and system acclimation for patients to experience the full extent of benefits.

Reserve antidepressants for patients with terminal conditions that have longer prognoses. Common undesired effects (or desirable effects in some cases) that may help to distinguish the best agent for your patient include sexual dysfunction, weight gain, sleep, energy, anxiety, and pain. Note that the monoamine oxidase inhibitor (MAOI) class of antidepressants (phenelzine (Nardil®), (tranylcypromine (Parnate®) is typically not used as initial therapy in the general population nor initiated in hospice. Please consult your pharmacist for guidance if your patient is taking a MAOI.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Agents: Citalopram (Celexa®), Escitalopram (Lexapro®), Fluoxetine (Prozac®), Fluvoxamine (Luvox®), Paroxetine (Paxil®), Sertraline (Zoloft®)
Indicated for: Prognosis ~ 6 months
Consider for: Concomitant anxiety, psychomotor slowing
Avoid/Caution in: Concomitant agitation, insomnia (particularly fluoxetine and sertraline), sexual dysfunction concerns
Notes: Citalopram and sertraline have a lower potential for drug-drug interactions. Fluoxetine and Paroxetine have a higher potential for drug-drug interactions.

Other Agents similar to SSRIs

Vortioxetine (Trintellix®)

Indicated for: Prognosis ~ 6 months
Consider for: Concomitant psychomotor slowing
Avoid/Caution in: Nausea concerns
Notes: Combination serotonin reuptake inhibitor and serotonin receptor antagonist

Vilazodone (Viibryd®)

Indicated for: Prognosis ~ 6 months
Notes: Combination serotonin reuptake inhibitor and serotonin receptor partial agonist

Selective Norepinephrine Reuptake Inhibitors (SNRIs)

Agents: Duloxetine (Cymbalta®), Venlafaxine (Effexor®), Desvenlafaxine (Pristiq®), Levomilnacipran (Fetzima®)
Indicated for: Prognosis ~ 6 months
Consider for: Concomitant neuropathic pain, psychomotor slowing, anxiety
Avoid/Caution in: Hypertension, agitation or insomnia, sexual dysfunction concerns

Heterocyclic Antidepressants

Agents: Mirtazapine (Remeron®), Trazodone (Desyrel®)
Indicated for: Prognosis ~ 6 months
Consider for: Concomitant insomnia (mirtazapine, trazodone), appetite loss (mirtazapine), agitation (mirtazapine), sexual dysfunction concerns
Avoid/Caution in: Overweight concerns
Notes: Not considered first-line therapy without concomitant indications for use.

Tricyclic Antidepressants (TCAs)

Agent: Amitriptyline (Elavil®), Desipramine (Norpramin®), Doxepin (Sinequan®), Imipramine (Tofranil®), Nortriptyline (Pamelor®)
Indicated for: Prognosis ~ 6 months
Consider for: Concomitant insomnia and/or neuropathic pain
Avoid/Caution in: Structural heart disease, concomitant medications that prolong QT interval
Notes: Not considered first-line therapy. Anticholinergic properties may be poorly tolerated by geriatric patients.

Aminoketones

Agents: Bupropion (Wellbutrin®, Wellbutrin® SR, Wellbutrin® XL)
Indicated for: Prognosis ~ 6 months
Consider for: Patients with low energy (mild stimulant effects), overweight concerns, sexual dysfunction concerns
Avoid/Caution in: Seizure history (decreases seizure threshold), patients with insomnia
Notes: Adjunct therapy ONLY.

Psychostimulants

Agent: Methylphenidate (Ritalin®)
Indicated for: Prognosis ≤ 6 months
Consider for: Patients with short prognosis and goals consistent with maintaining alertness and energy level
Avoid/Caution in: Concomitant anxiety, agitation, appetite loss
Notes: Onset within a few days & limited to several-week effectiveness with side effects increasing over time. Most effective for short-term treatment of refractory depression.

 

How do I manage to switch from one antidepressant to another?

When changing from one antidepressant to another (for example, to a medication included in the hospice formulary), consider the patient’s history and prognosis first.  If a patient has a history of depression and symptoms have been stabilized on their current medication, it may be more beneficial for the patient to continue that medication, especially if the prognosis is days to weeks. If symptoms are new and/or the patient has been on an antidepressant for a short time and prognosis is months, switching agents may be more appropriate. Monitor the patient and adjust the switching strategy for symptoms of withdrawal, side effects, or the return of symptoms of depression.2,3

Guide for switching from one agent to another:2-4

  1. Conservative switch or Moderate switch
    • Gradually decrease and then d/c the “old” agent followed by a washout period before initiating the “new” agent.
    • Washout periods are drug-specific and should allow time for the discontinued medication to be eliminated from the patient’s system. Full elimination is estimated by calculating 5 times the drug’s t1/2 (elimination half-life) (the time it takes for the plasma concentration of the drug in the body to decrease by half) (i.e., duloxetine’s t1/2 averages 12.5 hours so the washout period would be 62.5 hours (approx. 3 days).
    • This approach is not practical or recommended in hospice. Discontinuation of one agent, leaving a gap of time before starting another agent, can cause discontinuation syndrome (dizziness, irritability, nausea, fatigue) or symptom recurrence. Discontinuation syndromes are of most concern when switching from a serotonergic agent (i.e., SSRI, SNRI) to a non-serotonergic agent (i.e., heterocyclic, TCA).
  2. Direct or Next Day switch
    • Appropriate for when the “old” agent and “new” agent are in the same class or similar classes (i.e., SSRIs and SNRIs). Last dose of “old” drug taken one day and then “new” drug initiated at the same time of day the next consecutive day at a low dose. Gradually increase to effect.  Note that Fluoxetine has a long half-life, so wait 4-7 days before starting new agent if fluoxetine is the “old” drug.
  3. Cross-taper switch
    • Appropriate for when the “old” drug and “new” drug are NOT in the same class and for patients at high risk of symptom/illness relapse. Cross-tapering involves gradually increasing the “new” drug while decreasing the “old” drug so that patient is taking both antidepressants simultaneously.
    • Tapering down “old” agent example: Decrease dose by 25% every week until dose is at a low/initial starting dose (i.e., for “Sertraline 100mg Daily”-  Week 1: 75mg/day, Week 2: 50mg/day, Week 3: 25mg/day, Week 4: D/C)
    • Gradually increasing “new” agent example: Increase dose by 25% every week until dose is at therapeutic dose (i.e., for “Mirtazapine”- Week 1: 7.5mg/day, Week 2: 15mg/day, Week 3: 30mg/day, Week 4: Continue 30mg/day if therapeutic or consider increase to 45mg/day)
    • Drug-specific notes:
      1. Taper/gradually increase paroxetine over at least 4 weeks.
      2. Taper/gradually increase other SSRIs, venlafaxine, and duloxetine for a total of 1-4 weeks
        • Sertraline or venlafaxine, by 25 to 50 mg/day every 1-2 weeks
        • Paroxetine or citalopram by 5 to 10 mg/day every 1-2 weeks
        • Escitalopram by 5 mg/day every 1-2 weeks
      3. Literature is lacking for switching to/from vilazodone or vortioxetine to another agent. Consider managing the same as SSRIs due to the serotonergic mechanism. Follow manufacturer’s recommended titration schedule when starting vilazodone.
      4. Literature is lacking for switching to/from desvenlafaxine or levomilnacipran to another agent. Consider managing as venlafaxine due to a similar mechanism of action.

PHARMACIST ASSESSMENT

NW has a cardiac disease in which depression is common.  Her medication list contains drugs that may precipitate depression symptoms (carvedilol, furosemide, spironolactone, morphine) however, she has been on these medications for some time now and her depressive symptoms started recently.  Her other symptoms, including pain and breathlessness, are generally well controlled. Based on assessment in collaboration with the hospice medical director, it is determined that the patient is experiencing a new onset unspecified depressive disorder. NW has been taking duloxetine for two weeks and her prognosis is estimated to be several months. The hospice wishes to switch to a formulary medication and the family agrees.

recommendations

  1. Assess timing of furosemide dosing to prevent nighttime waking to use a bathroom. Consider timing 2nd furosemide dose in the afternoon to minimize nighttime disruption of sleep.
  2. NW has had a positive initial response to duloxetine. To minimize discontinuation symptoms, switching to an agent with serotonergic properties will provide a smooth transition.
  3. Direct or Next Day switch: When patient/family is ready, have NW take the last dose of duloxetine on Day 1. At the same time of day on Day 2, begin citalopram 20mg po daily.

 

DOWNLOAD A COPY OF THIS CASE STUDY

Click here, Depression Management Case, to download a copy of this case study.

 

FOR ADDITIONAL INFORMATION ON THIS TOPIC, PLEASE REVIEW THESE REFERENCES:

Enclara Pharmacia’s On Demand Educational Webinar, “Delirium, Depression, and Anxiety at End of Life”. Click here to log in to Enclara Client Portal.

  1. Fairman N, Hirst JM, Irwin SA. Clinical manual of palliative care Psychiatry. 1st Arlington: American Psychiatric Association; 2016.
  2. PL Detail-Document, Choosing and Switching Antidepressants. Pharmacist’s Letter/Prescriber’s Letter. July 2014.
  3. PL Detail-Document, Antidepressants. Pharmacist’s Letter/Prescriber’s Letter. July 2014.
  4. Keks N, Hope J, Keogh S. Switching and stopping antidepressants. Aust Prescr 2016;39:76–83. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919171/pdf/austprescr-39-076.pdf
  5. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2017. Access 2017 Feb. Available from: http://www.clinicalpharmacology.com
  6. GP Online. Switching and withdrawing antidepressants. http://www.mims.co.uk/news/882430/Switching-Antidepressants/ .
  7. Marangell LB. Switching antidepressants for treatment-resistant major depression. J Clin Psychiatry 2001;62(Suppl 18):12-7.
  8. Rosenstein DL. Depression and end-of-life care of patients with cancer; Dialogues Clin Neurosci. 2001 March;31(1): 101-108. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181973/
  9. Noorani NH and Montagnini M. Recognizing depression in palliative care patient. Journal of Palliative Medicine. 2007;10(2):458-464.
  10. Hirdes JP, et al. Predictors of caregiver distress among palliative home care clients in Ontario: Evidence based on the interRAI Palliative Care. Palliat Support Care. 2012;10(3):155-163.
  11. Wilson KG, et al. Diagnosis, and management of depression in palliative care, in Handbook of Psychiatry in Palliative Medicine, 2nd New York: Oxford University Press; 2009, pp 39-68.
  12. Rosenfeld B, et al. Does desire for hastened death change in terminally ill cancer patients? Soc Sci Med.2014;111:35-40.
  13. Zhang B, et al. Factors important to patients’ quality of life at the end of life. Arch Intern Med. 2012;172(15):1133-1142.

Leave a Reply

Your email address will not be published. Required fields are marked *