Suparna Madan BSc (CMMB), BSc (Psych), MD, FRCPC, Clinical Associate Professor, Section of Geriatric Psychiatry, Department of Psychiatry, University of Calgary
Monica is an 84-year-old widowed woman with a recent onset of atrial fibrillation, treated with warfarin. She presents with a one-month history of irritable mood, headaches, insomnia, weight loss, memory complaints and psychomotor retardation.
What factors should be considered when choosing pharmacological treatment for late life depression?
Depression in later life may be difficult to detect and adequate treatment is crucial to improve quality of life and reduce functional decline. Antidepressants have efficacy in the elderly (including elderly with multiple comorbidities) similar to younger adults; however antidepressant choice in later life is influenced by comorbid medical conditions, adverse effect profile and pharmacodynamic and pharmacokinetic changes with aging. Non-pharmacological options should not be overlooked as treatment options (both individually and in combination with other therapies).
DSM-5 diagnostic criteria for major depression include at least a two-week history of sustained low mood or anhedonia and four additional symptoms (including suicidality, guilt, worthlessness, changes in concentration changes, vegetative changes (sleep, appetite, energy) and psychomotor changes). However, due to proposed factors such as changes in brain blood flow, metabolism and neurotransmitter function, the presentation of depression in older adults may differ from the younger population. For example, elderly adults may present more commonly with non-specific somatic complaints, delusional symptoms and melancholy. They are also more likely to present with irritability rather than sadness. Sub-syndromal symptoms (i.e., less than five criteria) can still cause functional impairment in the elderly and should be considered for treatment.
Barriers to the diagnosis of depression later in life include reporting bias (for example, due to perceived stigma), assumption that depression is a natural phenomenon in response to loss, negative life events, physical decline and the obscuring effects of comorbid medical conditions.
General Principles of Antidepressant Choice
- Minimise the use of medications with:
- Long half-lives (such as fluoxetine)
- Anticholinergic properties (tricyclic antidepressants (TCAs), paroxetine) and cardiac adverse effects (TCAs).
- Significant drug interactions
- In patients with risk factors for developing hyponatremia or gastrointestinal (GI) bleeding, using antidepressants with less serotonergic effects (example, bupropion) should be considered. Prior to initiation of a serotonergic antidepressant (examples: selective serotonin reuptake inhibitors, venlafaxine, duloxetine), complete a baseline sodium and follow-up sodium levels (especially in symptomatic patients).
- In patients with liver disease, use antidepressants with limited cytochrome P450 (CYP) drug interactions. Desvenlafaxine is the active metabolite of venlafaxine (i.e., does not need to pass through the liver to became active) and therefore may confer a theoretical advantage in individuals with significant liver disease. Duloxetine should not be prescribed in patients with pre-existing liver disease or significant alcohol use due to risk of causing liver failure.
- Dose-dependent effect on blood pressure should be monitored with medications such as venlafaxine.
- QTc prolongation, a dangerous type of arrhythmia, may more commonly occur in the elderly. This effect is dose-dependent for some medications and as such Health Canada recommends a maximum dose of 20 mg for citalopram and 10 mg for escitalopram in the elderly. Minimal effects on QTc have been found with medications including sertraline, duloxetine and paroxetine. Bupropion may shorten QTc.
- In renal impairment, dose reduction may be required (for example, with venlafaxine, mirtazapine) and with severe renal impairment some antidepressants are not recommended, such as citalopram or duloxetine.
- Consider comorbid medical conditions when choosing antidepressants. For example:
- Vortioxetine may be helpful for depressed geriatric patients who have cognitive deficits.
- Mirtazapine tends not to cause GI adverse effects, may promote sleep at low doses and may improve appetite. Mirtazapine may also reduce drinking in patients with depression and comorbid alcohol use disorder.
- Bupropion can be stimulating, has lower risk of sexual adverse effects and has been used for smoking cessation. However it should be avoided in patients at risk for seizures.
- Duloxetine may reduce neuropathic pain, chronic musculoskeletal pain and stress urinary incontinence.
Dosing and Administration
- Typical starting dose in the elderly is 50% of the regular adult starting dose, but should titrate to the average dose within month, if tolerated.
- If there is no response at two weeks at the average dose, further slow titration should be considered.
- In patients who are unable to swallow medications, consider use of rapidly disintegrating forms (examples include mirtazapine and citalopram), liquid formulations (paroxetine, citalopram) and crushing of non-extended release medication. Additionally, capsules of venlafaxine extended release may be opened and the contents sprinkled over apple sauce (providing contents are not otherwise disrupted).
- Confirm the diagnosis:
- For example, does the patient have a hypoactive delirium, bipolar disorder, apathy secondary to dementia, psychotic depression, or is there an organic condition, substance or medication adverse effect causing the depressive symptoms?
- Presuming the diagnosis is correct:
- Ensure medication has been tried at the maximally tolerated dose and continue medication for an appropriate length of time (noting elderly may take longer than the 4-6 weeks for the younger population to show full benefit from medication).
- Address potential barriers to compliance (cost of medication, cognitive deficits, death of caregiver, complicated dosing regimen, etc.).
- Switch to another first line agent if no response on initial agent or combine/augment with another antidepressant or mood stabilizer if there is a partial response (for example, there is evidence for Lithium augmentation).
- To minimize withdrawal syndrome, tapering off the initial antidepressant when switching medications should be considered for short-half medications, medications without active metabolites and patients with treatment emergent anxiety. For example, venlafaxine and paroxetine should be tapered.
- If a switch is occurring from a monoamine oxidase inhibitor, a longer wash-out period is required.
- Augmentation choice should consider targeting residual symptoms. Non-pharmacological strategies (such as cognitive behavioural therapy, interpersonal therapy, behavioural activation) should also be considered.
- Neuro-brain stimulation (electroconvulsive therapy, transcranial magnetic stimulation) can also be considered in consultation with a specialist.
Follow-up and Long-Term Maintenance
- After initiating an antidepressant, patients should be seen weekly, at least for several weeks for the purpose of monitoring adverse effects and improvement (and need for dose titration), and supportive psychotherapy.
- Note, although the increased suicide risk evident in adolescents and children initiated on antidepressants is not evident in the adult population, suicidality may emerge in depressed patients and patients with pre-existing suicidal ideation may be ‘activated’ by early improvement in vegetative symptoms. Therefore suicide risk during treatment should be evaluated regularly.
- Depression with onset for the first time later in life may be prodromal for dementia and therefore cognition should be monitored over the long-term.
- For a first episode of depression, medication should be continued for at least a year, up to two years. For a recurrent episode in the elderly or if an initial episode is severe or only partially treated, indefinite maintenance treatment is recommended.
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