US Pharm. 2024;49(6):18-23.

ABSTRACT: Loneliness and isolation have emerged as a significant threat to mental health and physical well-being in the United States, prompting a national advisory by the Surgeon General. The consequences of loneliness can profoundly and substantially threaten our society, not only because it contributes to the risk of premature disability and death but also because it impairs social connections critical to relationships that are necessary to promote productivity and engagement at work, school, and within our community organizations. Men experience unique challenges of loneliness and are at higher risk of suicide. According to the Surgeon General, we should be equally as invested in addressing social isolation as we have been in our recent efforts to curb addiction and substance misuse.

As the tide of the COVID-19 pandemic continues to recede and we examine the mental health aftermath, it is becoming increasingly clear that we have all been changed by this event in ways that have yet to be understood. The gradual, ongoing decline of supportive social networks over the past 30 years, as evidenced by a decrease in the number of close friends reported by Americans, appears to have been only worsened by the pandemic and has spiked more recently.¹

For men, surveys are showing bigger gaps, with 15% reporting having no close friendships in 2021 compared with only 3% in 1990. For women, 10% report no close friends compared with 2% in 1990, respectively.¹ This same Survey Center on American Life May 2021 American Perspectives Survey also reveals that men are also far less likely to experience emotional support from a friend, with only 21% of men reporting having received support from a friend within the past week compared with double that (41%) for women.¹ Married men were more likely to turn to their spouse when they experienced a personal problem, with 85% of married men, compared with 72% of married women, doing the same. The gap was observed in unmarried men, with only 30% seeking out a friend to confide in compared with almost 40% of women talking to a friend about their problems. While the prevalence of loneliness and social isolation is higher in men, the prevalence appears to be high overall in both sexes. According to the Surgeon General, loneliness is emerging as a condition that has resulted in profound consequences. “Loneliness is far more than just a bad feeling—it harms both individual and societal health,” Dr. Vivek H. Murthy wrote.² Individuals who are experiencing loneliness, whether due to forced quarantine and isolation or other factors, are at higher risk of serious medical sequelae, including cardiovascular disease, dementia, and stroke in addition to psychiatric comorbidities of depression and anxiety. All of these health consequences can lead to premature death. According to Holt-Lunstad and colleagues, mortality rates associated with the impact of social isolation are similar to those caused by smoking up to 15 cigarettes per day. Even higher rates of mortality are associated with physical inactivity, leading to obesity and other consequences of sedentary behaviors.³ These compelling comparisons are reported in the Surgeon General’s advisory (see FIGURE 1).²

The association between the medical consequences of increased morbidity caused by cardiovascular disease and incidence of stroke is reported to be one of the strongest pieces of evidence connecting the impact of the lack of social connection to adverse health outcomes, with increases of 29% and 32% for each, respectively. It has become clear that these adverse effects begin during childhood, manifesting as an increased prevalence of obesity, elevated blood glucose, and high blood pressure as individuals age into adulthood. In 2022, the American Heart Association concluded that “social isolation and loneliness are common, yet underrecognized, determinants of cardiovascular health and brain health,” adding, “heart failure patients who reported high levels of loneliness had a 68% increased risk of hospitalization, a 57% higher risk of emergency department visits, and a 26% increased risk of outpatient visits compared with patients reporting low levels of loneliness.”² The percentage of the population with diabetes categorized by sex alone reported in 2020 for data collected from 2017 to 2020 was 15.4% (13.5%-17.5%) for men compared with 14.1% (11.8%-16.7%) for women.⁴ Looking at total numbers reported by the CDC in 2021, men continued to be diagnosed with diabetes at a higher overall rate than women, as shown in TABLE 1.⁴ Men and women alike can experience similar loneliness and isolation, but some groups are at higher risk, including individuals with poor mental or physical health, disability, financial insecurity, extreme age (young or old), or those who are living alone.²

What Is Causing the Loneliness Epidemic?

There are many hypotheses regarding the current and long-term impact of loneliness. Membership in civic and religious organizations that have been important pillars of past community connection have declined significantly since 1999. At that time, 70% of Americans reported belonging to a church, synagogue, or mosque, but in 2020, less than 50% indicated memberships in these religious organizations. This represented the sharpest decline in this survey measure.^5-7 Societal polarization, exacerbated by the drive to reduce discussion networks, leads to a more politically homogenous circle. This has led to a trend of more than half (60%) of respondents admitting to stress and frustration when discussing politics with people who hold different opinions, and even more (64%) reported that they were incapable of having constructive, civil debates about contentious issues.⁸

The Surgeon General’s report also highlights the complex impact that rapidly evolving technology, including the vast array of social media platforms, has had on our relationships and health. In some ways, technology can connect us by facilitating outreach opportunities that might otherwise not be possible; however, it also can lead to harms, including displacing our in-person interactions, reducing the quality of engagement, and negatively impacting self-esteem—leading to an even greater degree of loneliness and psychiatric consequences, such as depression.^9-11

Psychiatric Consequences

Mann and colleagues note that individuals who report frequently feeling lonely have more than double the risk of developing depression than those who report rarely or never feeling lonely.¹² Individuals who develop anxiety, depression, or both are at even higher risk of loneliness and isolation resulting from the social withdrawal associated with the course of illness.²

For men, deaths due to suicide are strongly associated with objective indicators of isolation, such as living alone. In a study conducted by Shaw and colleagues examining more than 500,000 middle-aged adults, the authors reported that the probability of dying by suicide was more than double among men who lived alone.¹³ Circumstances that foster perceptions of a low sense of belonging and of being a burden to others, together with diminished or absent social support, are associated with increased suicidal thoughts (ideation).¹⁴

Pharmacologic Interventions 

Anxiety

Generalized anxiety disorder (GAD) is among the most commonly observed anxiety disorders seen by primary care providers.¹⁵ Because GAD can manifest with physical chief complaints, patients may not be aware that they are experiencing mental health challenges. There are numerous guidelines that inform prescribing for treating the symptoms of GAD, with variations that provide clinical flexibility; however, the consensus is that scheduled antidepressants, especially the selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, are the recommended first-line gold standard pharmacologic treatment for GAD. Most guidelines also recommend psychotherapy as first line, often in addition to pharmacotherapy, to offer the greatest benefit.¹⁵

The sexual side effects associated with antidepressants can be a challenge for both sexes. However, men experience the uniquely male sexual symptoms of erectile dysfunction and ejaculation failure in addition to the common denominator of decreased male and female libido. Patients who experience sexual side effects with antidepressants can explore other nonantidepressant FDA-approved treatments that include the sedating antihistamine hydroxyzine, which is anxiolytic yet is also highly anticholinergic and can exacerbate existing benign prostatic hypertrophy in men. Buspirone is yet another option for anxiety, but as is the case with the antidepressant agents, it must be taken on a scheduled basis whether or not the patient feels symptomatic.¹⁶

Depression

The evolution of antidepressants has yielded a wide array of FDA-approved medications with different mechanisms of action, and thus different side-effect profiles, to promote a customizable patient side-effect experience. The FDA boxed warning that describes increased risk of suicide for adolescents and young adults does not apply to older adults, and in fact, the FDA prescribing information reports that the use of antidepressants in adults aged 65 years and older resulted in fewer cases of suicidality in the older population (see TABLE 2).¹⁷

Presenting similar challenges to when antidepressants are prescribed for anxiety, sexual side effects can pose a barrier to their use; however, unlike the treatment for GAD, there are currently no nonantidepressant pharmacologic alternatives approved by the FDA that are also recommended as first-line intervention for major depressive disorder (MDD).¹⁶ Fortunately, more antidepressant options are available for the treatment of MDD that utilize different mechanisms of action and have different side-effect profiles. Some antidepressants are associated with a lesser risk of these side effects, such as bupropion and mirtazapine, which have been considered sexual symptom–sparing.¹⁸

Insomnia

The architecture of sleep changes over a lifetime; however, with co-occurring anxiety and depression, the risk of insomnia increases. While sleep hygiene recommendations offer concomitant benefits to augment cognitive behavioral therapy and pharmacotherapy, their use is considered a suboptimal intervention when employed exclusively to manage patients with chronic insomnia.¹⁹ It is important that healthcare providers not dismiss complaints of insomnia, since the sleep disorder is significantly associated with an increased risk of depression.²⁰ Insomnia is recognized as an important public health challenge that requires both an accurate diagnosis and effective treatment to improve sleep quality and insomnia-related daytime impairment.²¹

There are currently many pharmacologic options available for the short-term treatment of insomnia. We now recognize the necessity of sex-based dosing for certain medications; however, there are limited FDA sex-based recommendations for insomnia medications. Currently, only zolpidem—one of the benzodiazepine receptor agonists—includes sex-based, FDA-approved dosing. For men, the initial recommended dose is 10 mg. For women or men who need a lower single dose, 5 mg immediately before bedtime with at least 7 to 8 hours remaining before the planned awakening time is the suggested regimen.²²

Conclusion

With recent estimates suggesting that increasing social connection can boost the odds of survival by 50%, it is essential for healthcare providers to include focused support in this area just as we would toward other risk factors, including hypertension, obesity, and metabolic complications.²³ What can we do beyond recommending optimal pharmacotherapy for the medical and psychiatric consequences of loneliness and isolation? According to the Surgeon General’s report, healthcare providers can take the following actions²:

Acknowledge Social Connection as a Healthcare Priority: Past practices in addressing nicotine addiction, opiate addiction, and obesity have demonstrated success in efforts to move in a positive direction once we unify behind a common goal with a purpose.

Focus on Formal Training on the Importance of Social Connection: Pharmacists, nurses, and prescribers should seek continuing education on risks associated with isolation and low social supports, including negativity and isolation. Those with expertise in this area could develop and provide advanced training on prevention and optimal interventions to address this health disparity.

Recognize Those at Higher Risk: This category includes individuals with physical or mental health conditions, those with disability, those living alone, those of advanced age, and those with financial insecurity. Consider asking these questions on intake to assess the level of social connection whenever possible. Educate and incentivize patients to understand the risks of inadequate social connection and how addressing disconnection may be part of their overall primary prevention of disease and disability. Providing specific examples to compare risks associated with lacking social connection as being worse than smoking up to 15 cigarettes a day, drinking six alcoholic drinks per day, physical inactivity, and obesity can be effective motivation for patients. Be prepared to offer resources that provide psychosocial support to patients that may include involving family or caregivers. Resources can include group therapy and other evidence-based treatment options.

Integrate Social Connection in Patient Care in All Healthcare Settings: Proactively assess the level of social connection and educate patients about the benefits of social connectedness as a means of primary prevention along with other healthy lifestyle recommendations.

Efforts that we can undertake as a healthcare community to support and strengthen the pillars established by the Surgeon General’s report include, but are not limited to, expanding public health surveillance and interventions. In addition, cultivating a culture of connection, kindness, respect, and commitment to one another can help promote health and increase resilience within ourselves and our patients.

REFERENCES

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