Can medications be used to solve loneliness?

Background

Loneliness is recognized as a significant public health issue – being a consistent and strong predictor of poor physical health and premature death (Shankar et al., 2011). Although there is growing interest in identifying and implementing effective interventions, most of these offer only moderate, short-term benefits (Cacioppo et al., 2015; Masi et al., 2013). Interventions that are more effective often require significant investments of time and energy to deliver. Given these challenges, researchers have sought to assess whether prescription medications might help reduce loneliness (Cacioppo et al., 2015). While such an approach fails to address the underlying social challenges that contribute to loneliness, there is growing evidence that loneliness implicates physiological mechanisms, which might contribute to the maintenance and severity of loneliness (Morr et al., 2022; Pourriyahi et al., 2021). Indeed, genetics, neuroimaging, and other biomarker studies increasingly suggest that loneliness is both influenced by and contributes to biological processes (Brilliant et al., 2022; Nakagawa et al., 2015; Cacioppo et al., 2016). Other epidemiological studies support this showing a high level of genetic and biological heritability of loneliness (Spithoven et al., 2019; Goossens et al., 2015; Day et al., 2018) and strong within-person stability of trajectories of loneliness (Mund et al., 2019, 2020). As well, it is hypothesized that loneliness triggers fundamental stress physiology and in turn creates hypersensitivity to social threat, which causes withdrawal, which worsens loneliness – thereby creating a vicious cycle that inculcates loneliness (Ahmed et al., 2023; Hawkley & Cacioppo, 2013). Given these physiological connections, prescription medications and therapies might be leveraged to disrupt this cycle.

Purpose

The purpose of this evidence brief is to review potential pharmaceutical approaches to address loneliness.

Evidence from Existing Studies

Prescription medications are potentially powerful tools for the treatment of mental health conditions. An emerging body of research over the past several decades suggests that these medications might be prescribed to reduce loneliness. Several plausible mechanisms have been identified and medications have been proposed to leverage these mechanisms in the treatment of loneliness.

Perhaps the most important ways that prescription medications can help address loneliness is by reducing multi-morbidities which lead to social exclusion and isolation. Indeed, the onset of multi-morbidity has been shown to contribute to greater levels of loneliness (Schubbe et al., 2023); researchers have highlighted a wide variety of reinforcing mechanisms linking poor physical health and loneliness (Quadt et al., 2020; VanderWeele et al., 2012). For example, hearing loss, chronic inflammation, poor mobility might reduce incentives for social participation or make social interactions difficult. Therefore, addressing these factors through the prescribing of medications could also address loneliness (Keesom & Hurley, 2020; Eisenberger et al., 2023). As well, addressing other health limitations to increase activity might allow people to address loneliness through other forms of community participation (Broen et al., 2023; Surkalim et al., 2024; Franke et al., 2021; Ahn et al., 2024).

In addition to addressing the contributors to loneliness, some researchers have argued that it might also be possible to directly address experiences of loneliness using medications (Cacioppo et al., 2015). Such approaches include the use of selective serotonin reuptake inhibitors to address anxiety (SSRIs; e.g., fluoxetine; Schneier, 2001; Pinna, 2011; Guarnieri et al., 2020), neurosteroids to help restore homeostasis to the stress response (e.g., allopregnanolone; Evans et al., 2012; Cacioppo & Cacioppo, 2015), or oxytocin to improve bonding (Tsai et al., 2019; Grippo et al., 2009; Berger et al., 2024; Elheja et al., 2021; Kosfeld, 2005; Ishak et al., 2011). With each of these examples, there is a hypothesized opportunity to end the cycle of loneliness by interfering with the underlying biological drivers that reinforce antisocial or maladaptive forms of cognition and behaviour. However, it is important to note that most of the studies supporting these approaches remain in animal testing, come from observational evidence, or may have unintended consequences (Hoekstra, 2010; Olff et al., 2013). For example, studies have shown that oxytocin administration can drive in-group cohesion, but amplify outgroup aggression (Zik & Roberts, 2015; De Dreu et al., 2010). Such findings highlight the need for caution when intervening on these sensitive biopsychosocial processes that give rise to experiences of loneliness—particularly given the heterogenous effects such interventions might have across populations with different experiences of loneliness (Niesink & Ree, 1982; Dankoski et al., 2014).

While pharmaceuticals might be used to help address loneliness and contributing health conditions, its important to note that evidence examining the use of depression and anxiety prescription medications indicates that they are actually associated with increased loneliness – questioning whether the medications actually have a meaningful effect on mental health and social wellbeing(Lam & Vuolo, 2023). Indeed, it is already common practice to treat psychiatric conditions with pharmaceutical prescriptions (Im et al., 2023), but yet many of those receiving such prescriptions do not experience improvements beyond those expected from non-pharmaceutical interventions. Similar challenges have been highlighted with other mental health challenges, such as post-natal depression in new mothers (Leahy-Warren & McCarthy, 2007) – highlighting the potential challenge of addressing loneliness using traditional treatment approaches.

Another potential mechanism that prescription medications might take advantage of in order to address loneliness is the re-opening of the “critical period” for social development. Critical periods are specific times during human development when the brain is particularly receptive to certain stimuli that are necessary for development (Cisneros-Franco et al., 2020). During these windows, experiences have a profound impact on the brain's structure and function, effectively shaping future behaviors and abilities. Once these periods close, the brain's plasticity in those areas significantly decreases, making it more challenging to alter those pathways later in life. In humans, critical periods are observed in various developmental stages, such as language acquisition, sensory development, and social behavior. For example, the critical period for social development appears to take place during adolescence and childhood (Crone & Achterberg, 2021; Tazanoulinou & Sandi, 2017). The concept of re-opening critical periods has gained interest in the field of neurology and psychiatry, especially in relation to treating conditions like autism or social anxiety. Certain prescription medications might be designed to temporarily enhance brain plasticity, thereby allowing adults to re-learn or improve social skills that are usually solidified during childhood. For example, researchers are actively exploring the use of psychedelics, including MDMA, as a means of re-opening the critical period of social development (Lyubomirsky, 2022; Nardou et al., 2019, 2023; Lepow et al., 2021) or by otherwise promoting empathogenic effects (Bedi et al., 2010). Preliminary research on the naturalistic use of psychedelics provides promising results and clinical research continues to demonstrate potential (Kettner et al., 2024; Weiss et al., 2021) – however some evidence suggests that the social stigma surrounding psychedelics and other drugs may undermine social cohesion (Rokach, 2001), emphasizing that the effects of these therapies must be socially contextualized.

While medications might provide an opportunity to address loneliness, caution should be taken to avoid over-prescribing – particularly given that lonely individuals are more likely to be prescribed certain drugs, including opioids and benzodiazepines (Kotwal et al., 2021; Vyas et al., 2021). Furthermore, given that evidence examining the causes of mental health conditions point towards these experiences serving as functional responses to environments rather than merely the bi-product of chemical imbalances in the brain (Tripathi et al., 2019; Moncrieff et al., 2022), caution must be taken to not rely on medical solutions that fail to address environmental and social causes of loneliness (e.g., family issues; poor peer relationships; and social media; Wahid et al., 2022; Galesi, 2013). In other words, as loneliness is inherently an indicator of unmet social needs, meeting these social needs must be a critical component of any treatment approach (Cacioppo & Patrick, 2008). As well, speaking to the importance of these social conditions, studies emphasize that therapeutic relationships may augment the placebo response by providing a sense that individuals are being cared for (Wampold, 2018). As such, studies that aim to demonstrate the effectiveness of medications require high quality study designs with appropriate and consistent controls.

Finally, in addition to considering the role of prescription medications in reducing loneliness, caution must also be taken when prescribing medications – particularly since some studies have shown that some medications may unintentionally reduce feelings of connectedness (Inagaki et al., 2016). Pharmacists may therefore play a role in reducing loneliness, not by facilitating prescriptions, but by helping identify potential challenges among patients working to ensure they receive appropriate, non-contraindicated care (BC Pharmacy Association, 2018).

Analyses from The Canadian Alliance for Social Connection and Health

The Canadian Social Connection Survey includes limited data on medication use. However, the survey did included information about whether participants with co-morbidities received treatments and whether these treatments have reduced participation restrictions. Importantly, greater activity restrictions due to depression (β = 0.83, SE = 0.12, p < 0.001) and anxiety(β = 0.72, SE = 0.13, p < 0.001) are associated with greater loneliness; but previously receiving treatment for depression (Currently: β = -0.25, SE = 0.36, p = 0.488; Previously: β = -1.01, SE = 0.36, p = 0.006) and anxiety (Currently: β = 0.00, SE = 0.26, p = 1.000; Previously: β = -0.55, SE = 0.27, p = 0.045) were associated with reporting lesser activity restrictions due to these conditions. In other words, while we cannot specifically evaluate effectiveness of medications in the treatment of loneliness, these analyses support the hypothesis that the treatment of co-morbidities and subsequent reduction in activity limitations may reduce loneliness among those with other health issues. The non-significant effects of treatments on activity restrictions for those currently on treatment may be likely due to ongoing unresolved treatment. However, when treatments are successful and efficacious they appear to have a positive effect.

Discussion

The potential role of prescription medications in addressing loneliness is complex and multifaceted, as highlighted by various studies exploring both direct and indirect mechanisms. While certain medications have been suggested to mitigate the physiological and psychological contributors to loneliness, such as multi-morbidities and stress responses, the evidence remains mixed. Some pharmacological approaches, like the use of SSRIs, neurosteroids, oxytocin, and even psychedelic therapies offer theoretical benefits by targeting underlying biological processes that may perpetuate loneliness. However, empirical support for these interventions is primarily limited to preclinical studies or derives from observational data with inherent limitations.

Given the state of the literature, we caution that while medications can play a role in alleviating certain aspects of loneliness, they do not address its social determinants. The role of environmental and social factors in exacerbating loneliness suggests that any effective intervention must incorporate a broader, more holistic approach that includes enhancing social support systems and community engagement. That said, when aligned with high quality clinical evidence, the use of pharmaceutical approaches to address co-morbidities may be beneficial. However, the benefit to reduced loneliness is contingent on the overall effectiveness of these approaches in the causal pathway linking comorbidities to loneliness. As such, specific investigations of these are needed.

Conclusion

Based on the available evidence, we recommend that medical interventions to address loneliness focus on addressing immediate barriers to participation. At this time, pharmaceutical approaches, while potentially promising, lack sufficient supporting evidence and may cause unintended consequences and harms. Further research into these approaches is needed, particularly to assess whether they can be leveraged to disrupt harmful and reinforcing cycles that perpetuate loneliness. Until such evidence is ready, established clinical guidelines for addressing loneliness should be followed (See CCSMH, 2024).