Higher frequency of side effects in older patients taking antidepressants

Relation

Sobieraj DM, Martinez BK, Hernandez AV, et al. Side effects of pharmacological treatments for major depression in older adults.J Am Geriatr Soc. 2019;67(8):1571-1581.

Objective

To evaluate the side effects of pharmacological antidepressants for the treatment of major depressive disorder (MDD) in adults aged 65 years and older.

Draft

Meta-analysis of 19 randomized controlled trials and 2 observational studies, most of which considered treatment in the acute phase (<12 weeks) of moderate-severity MDD.

Participant

Patients aged 65 years and older with MDD who were taking low-dose antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone, or vortioxetine, were compared with patients receiving other antidepressants. Placebo or non-pharmacological therapy.

Study parameters assessed

Adverse events during treatment of MDD, such as arrhythmias, cognitive impairment, falls, fractures, hospitalizations, mortality, and QTc prolongation, were assessed. Serious adverse events and discontinuations due to adverse events were also assessed.

Primary outcome measures

The different pharmacological treatments were compared in terms of the frequency of adverse events.

Key insights

There were 3 key findings in this meta-analysis:

1. Bei Patienten im Alter von 65 Jahren oder älter waren sowohl SSRIs als auch SNRIs mit signifikant mehr Studienabbrüchen aufgrund allgemeiner unerwünschter Ereignisse verbunden als Placebo.
2. In der akuten Phase der Behandlung (< 12 Wochen) traten bei Patienten, denen SNRIs, aber keine SSRIs verschrieben wurden, im Vergleich zu Placebo häufiger unerwünschte Ereignisse auf.
3. Das SNRI Duloxetin erhöhte spezifisch und signifikant die Anzahl der Stürze bei älteren Patienten, insbesondere bei Patienten mit Herz-Kreislauf-Erkrankungen, eine Tatsache, die in den ursprünglichen Studien zu wenig berichtet wurde.

Practice implications

Significant depression symptoms are common in the elderly, with rates of 15% to 20% in community-dwelling adults and higher in those with a medical illness or in an institution.¹Depression symptoms in seniors may present differently than in non-seniors. As a result, depression may not meet the usual criteria for major depression. In general, older patients experience more somatic complaints and cognitive symptoms, with fewer complaints of sad or dysphoric mood. Often depression in older people is seen as agitation, hypochondria or dementia syndrome, and these can often occur without complaints of sadness.^2.3

Prescription antidepressants are a concern for older patients due to the slower release of medications as well as the greater likelihood of drug interactions, as this population generally takes more medications. The American Geriatric Society recommends that SSRIs and tricyclic antidepressants (TCAs) should not be prescribed to seniors with a history of or significant risk of falls or fractures.⁴Because of their ability to increase acetylcholine levels, TCAs are generally not recommended for elderly care.

This study is a helpful reminder that even among medications considered “safer” for seniors, there are still concerns about the benefit-risk profile of these medications. With this in mind, naturopathic medicine could serve this population well by providing a more comprehensive mental health treatment plan.

Older patients may be at greatest risk of nonresponse to initially selected medication and appear to be at greater risk of recurrent depression once remission is achieved.⁵

Given this information about adverse events and the fact that older patients are at higher risk of recurrence, we as naturopathic physicians must strive to offer our patients natural treatment recommendations that have clear benefits in curing the underlying pathology of depressive illness. For example, hippocampal atrophy is known to be a signature of depression and cognitive decline. A study of 120 older adults with dementia showed that subjects who performed moderate-intensity aerobic exercise 3 days per week for 1 year showed increased hippocampal volume (by 2%), and this activity effectively reversed any age-related loss of brain volume. The expected brain loss was observed in control subjects who did not perform aerobic exercise, but instead only performed stretching and muscle training.⁶

Even among medications that are considered “safer” for seniors, there are still concerns about the risk-benefit profile of these medications.

Simple lifestyle supplements can also be of value. In a 10-year cohort study of more than 50,000 older women, researchers found that those who drank 2 to 3 cups per day had a 15% lower risk of depression compared to those who drank 1 cup or less of caffeinated coffee per week, and those who drank 4 cups or more had a 20% lower risk. For older people who are prone to depression, daily consumption of caffeinated coffee can be useful.⁷Other studies have found this hormonal support⁸was helpful in treatment-resistant depressed older women and in the treatment of lead exposure⁹can improve cognitive function.

Non-pharmacological supplementation can also help avoid the need for medication. MRI studies in depressed geriatric patients found that imbalances in the prefrontal cortex could be corrected with the use of acetyl-L-carnitine.¹⁰Low-dose fish oil therapy in 66 elderly patients (1,000 mg total, broken down to approximately 300 mg EPA and DHA) provided clinical benefit and had a much greater effect than placebo in another double-blind, randomized, placebo-controlled trial. which showed significant differences in the geriatric depression scale after accounting for confounding factors such as body mass, thyroid dysfunction and cholesterol.¹¹

restrictions

Overall, although this analysis was strong and helpful, some limitations are worth noting.

First and most importantly, the antidepressant doses studied reflected the lower limit (or lower half) of the recommended usual range for older adults. Second, none of the studies reviewed were actually designed to assess adverse events. Third, the analyzes on which these results were based excluded patients with multiple comorbidities or other neuropsychiatric illnesses such as dementia or a high risk of suicide. These first 3 limitations taken together may have resulted in underreporting of adverse events.

Because only single randomized controlled trials were available for certain medications, the authors said they were limited in their ability to detect side effects of bupropion, mirtazapine, trazodone, or vortioxetine. Therefore, these medications can also be a cause for concern.

Finally, because the authors did not have data that allowed them to assess whether harms differed by patient gender, we cannot say whether this information applies disproportionately to men or women.