May/June 2021

Medical Monitor: Medical Treatment of Depression
By Abimbola Farinde, PharmD
Today’s Geriatric Medicine
Vol. 14 No. 3 P. 6

Clinicians must keep the special needs of geriatric patients in mind.

Depression is one of the most commonly encountered psychiatric disorders in the United States, affecting approximately 8% of Americans and contributing to more than $210 billion in health care costs annually. In 2015, roughly 16.1 million adults experienced at least one major depressive episode in the previous year.1

While not all depressive symptoms can contribute to significant impairment in functioning, it’s typically those that lead to disability and associated health care costs that are presented to the public. Approximately 1% to 5 % of older adults live with depression, and this incidence may be higher among home health care or hospital patients. As the older adult population continues to grow and people live longer, the responsibility of understanding and managing concerns of aging increases.2 Older adults can face challenges such as loss of independence, loss of spouse, or health problems that can lead to depression, but depression isn’t a normal part of the aging process.3 While depression stems from a variety of psychological, environmental, and physical factors—including genetics, personality characteristics, and medication use—there are common and standard treatment approaches to management.

General Management Approach for Depression
Geriatrics patients represent a unique patient population, and their needs must be considered when it comes to therapeutic interventions for depression. The decision to treat can be based on the presence of a depressed mood that’s produced neurovegetative symptoms for four weeks or longer, as well as on a patient’s past episodes of depression, family history of suicide, or severe and disabling symptoms. There’s strong evidence to support the use of either pharmacotherapy or psychotherapy as monotherapy or in combination for the management of depression.4,5

Nonpharmacological Interventions
One widely used approach to treating depression in geriatric patients is psychotherapy, which has demonstrated moderate effectiveness. Some other commonly applied interventions can include cognitive behavioral therapy, problem solving therapy, interpersonal therapy, reminiscence and life review therapy, and brief psychodynamic therapy.6 Each of these interventions offers a specialized approach to addressing the underlying symptoms and cognitive distortions that can exist with depression.

If these approaches don’t produce the desired effects, another option is vagus nerve stimulation, which utilizes an implanted generator, wires, and electrodes to provide electricity to the vagus nerve to alleviate or eradicate the signs of depression.7 Another nonpharmacological intervention that can be considered on a case-by-case basis is deep brain stimulation, which is designed to provide stimulation of the neurons in the brain by means of an implanted generator and electrodes, as with vagus nerve stimulation.8

The strongest evidence for the effectiveness of nonpharmacological interventions has been established for cognitive behavioral therapy, problem solving therapy, and interpersonal therapy. Ultimately, the decision to take a nonmedical approach to depression treatment must be guided by an extensive review of the risks vs benefit of the applied interventions.

Pharmacological Interventions
When it comes to the decision to initiate pharmacotherapy in geriatric patients for depression, consideration should be given to the physiological changes that can accompany aging, the potential for polypharmacy, and cooccurring conditions.9 While there are different classes of antidepressants, each demonstrates similar efficacy in older populations. Several factors need to be considered when choosing an antidepressant for geriatric patients, for instance, the type of depression, drug side effect profiles, tolerability, patient preference, cost, and contraindications.10

With any antidepressant that’s initiated for late-life depression, the dose should begin at one-half that of the normal adult dose and then increased with tolerability and clinical response. Since there are specific neurotransmitters that have been correlated with depression—notably serotonin, norepinephrine, and dopamine—many antidepressants have been developed to target one or more of these neurotransmitters as a means of achieving symptom control.11

Monoamine Oxidase Inhibitors
One of the first classes of antidepressants developed were the monoamine oxidase inhibitors (MAOIs). Examples of MAOIs include tranylcypromine, phenelzine, and isocarboxazid. MAOIs work by inhibiting the monoamine oxidase enzymes A and B; this mechanism of action can lead to increased level of neurotransmitter activity. The use of these antidepressants has largely fallen out of favor due to their side effect profile and the necessity for users to avoid foods high in tyramine, such as aged cheeses or cured meats, due to the potential for hypertensive crisis. However, they can prove to be beneficial in cases of atypical depression (eg, hypersomnia, hyperphagia, mood reactivity) or when another intervention hasn’t worked.12

Tricyclic Antidepressants
Another type of medication is tricyclic antidepressants (TCAs), but these agents are typically not recommended as first-line agents for depression treatment in geriatric patients. This is largely due to the side effect profile of this class of agents, which includes anticholinergic effects, postural hypotension, visual disturbances, paresthesias, or cardiac conduction issues.13

TCAs, such as imipramine, nortriptyline, desipramine, and protriptyline, work by inhibiting the reuptake of serotonin and norepinephrine and blocking alpha-1-adrenergic , histamine-H1, and muscarinic acetylcholine receptors to different degrees.13 If the decision is made to utilize a TCA in a geriatric patient, an electrocardiogram, assessment of blood pressure, and blood level monitoring should be performed at baseline and during the course of treatment.14 Nortriptyline and desipramine are noted to be less likely to have anticholinergic side effects.

When initiating treatment with TCAs, clinicians should take a slow and gradual approach and ensure that the patient knows not to abruptly discontinue medication due to the risk of developing cholinergic rebound effect.14

The Effects of SSRIs and SNRIs
Selective serotonin reuptake inhibitors (SSRIs) are the most common type of antidepressants prescribed for all populations, including geriatric patients. These include fluoxetine, citalopram, paroxetine, sertraline, and escitalopram. SSRIs work by selectively inhibiting reuptake of serotonin, but they have little to no histaminic, muscarinic, or alpha-blocking activity.15 SSRIs are generally well tolerated in geriatric patients and can be used as first-line agents in the management of depression. Side effects, which are typically transient, include constipation, nausea, diarrhea, sexual side effects, and somnolence. If these persist, other agents may need to be prescribed.

Selective and norepinephrine inhibitors (SNRIs) include duloxetine, venlafaxine, and desvenlafaxine, which are considered to be potent inhibitors of serotonin and norepinephrine reuptake and weak inhibitor of dopamine uptake.16 SNRIs possess virtually no affinity for cholinergic, histaminergic, and alpha-1 adrenergic receptors. They are also well tolerated in geriatric patients and have been recommended along with SSRIs for long term care residents diagnosed with depression.14,17,18

Norepinephrine and Dopamine Reuptake Inhibitors
Another class of antidepressants is norepinephrine and dopamine reuptake inhibitors such as bupropion, which is a weak inhibitor of norepinephrine and dopamine whose effects aren’t fully understood.19 Bupropion isn’t considered to be first-line agent for depression but may be an alternative when other agents have failed. The minimal effect on serotonin, lack of inhibition of other neurotransmitters, and potential for seizure development in those with history of head trauma or seizures may limit use in this population.

Other Antidepressant Agents
Another class of antidepressant is the alpha-2 adrenergic antagonist such as mirtazapine. This drug works to block presynaptic alpha-2 receptors, both alpha-2 autoreceptors and alpha-2 heteroreceptors, to produce an increase in both norepinephrine and serotonin neurotransmission.20

Serotonin-2 antagonist reuptake inhibitors such as trazodone and nefazodone work by inhibiting the reuptake of serotonin, but also potentially block the serotonin receptors. Mirtazapine can serve as an alternative agent if SSRIs or SNRIs don’t produce a desired effect. Trazodone has the ability to block histaminergic and alpha-adrenergic receptors while nefazodone also has weak norepinephrine inhibition and weak alpha adrenergic blocking properties.20,21 Trazodone has been relegated to a sleep agent, but there are instances in which it can be used for depression as well. Nefazodone isn’t used in the United States at this time.

Last, one of the newer classes of antidepressants is the serotonin reuptake inhibitor/5-HT1A receptor partial agonist. Vilazodone, a drug in this class, inhibits presynaptic serotonin reuptake and has partial agonist activity at the 5-HT1A receptor.21 It’s known to cause nausea and diarrhea but is thought to have a lower risk of sexual side effects when compared with the majority of the other antidepressants.

Atypical Antipsychotics
When antidepressants fail to produce desired therapeutic effects, atypical antipsychotics such as olanzapine, risperidone, aripiprazole, or quetiapine can be used as adjunctive therapy, particularly in cases of treatment-refractory depression. Quetiapine, risperidone, and aripiprazole are the drugs in this class that have been extensively studied and have demonstrated efficacy, but their use must be evaluated against their side effect profiles, which includes a black box warning, FDA's most stringent warning, for increased risk of all-cause mortality in older patients with dementia.22 Before prescribing atypical antipsychotics in geriatric patients, providers must clearly assess the benefit vs risks.

Conclusion
The development of depression in geriatric patients can have a significant impact on quality of life. Depression can be caused by several factors, but it shouldn’t be viewed as a normal part of the aging process. The use of nonpharmacological and pharmacological interventions for depression management should be considered on an individual basis. Studies have shown psychotherapy to be effective and SSRIs to be first-line options. When selecting an intervention, clinicians should consider patient preference, side effects, cost, tolerability, and other relevant factors to determine the best course of therapy for a geriatric patient.

— Abimbola Farinde, PharmD, is a clinical pharmacy specialist with experience in the field and practice of psychopharmacology/mental health and geriatric pharmacy. A professor at Columbia Southern University, she has worked with active-duty soldiers with dual diagnoses of traumatic brain injury and a psychiatric disorder providing medication therapy management and disease state management. She’s also worked with mentally impaired and developmentally disabled individuals.

References
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