Breaking the cycle of loneliness: A randomized controlled trial of the anti-inflammatory naproxen in lonely, middle-aged adults.

BACKGROUND: Loneliness poses a major public health concern linked to many adverse health outcomes. One proposed pathway linking loneliness to poor health is inflammation, and there is growing evidence of a bidirectional relationship between the two. Additionally, both chronic loneliness and inflammation are associated with similar negative psychological consequences, such as heightened social threat sensitivity and negative cognitive biases. Given the relationship between loneliness and inflammation, it is possible that reducing inflammation may reduce loneliness and the negative psychological processes associated with it. Thus, this study investigated the effects of a non-steroidal inflammatory drug (NSAID) on loneliness, inflammatory activity, depressive and anhedonic symptoms, and affect during a social interaction.

METHODS: A parallel group randomized controlled trial examined the effect of an NSAID (naproxen) in a sample of highly lonely, healthy middle-aged adults. Participants took naproxen (400 mg; n=40 analyzed) or placebo (n=42 analyzed) daily for 2 weeks, completing a baseline, post-intervention, and follow-up session (2 weeks post-intervention). Participants reported on loneliness, depressive, and anhedonic symptoms at all three timepoints. Additionally, at baseline and post-intervention, participants provided a blood sample to assess inflammatory gene expression and completed a social interaction task to explore affective and affiliative behaviors in response to a conversation.

RESULTS: There were no significant treatment by time effects on any of the outcomes, except for inflammatory gene expression, which decreased in the naproxen-treated group. However, baseline perceived stress levels moderated treatment effects for several outcomes. Those with the highest baseline stress reported reductions in loneliness and anhedonia in the naproxen group. Similarly, during the social interaction task, those with higher baseline stress showed reduced negative affect and increased social approach behavior in the naproxen group. Surprisingly, those with lower baseline stress reported increases in loneliness and marginal increases in anhedonia in the naproxen-treated group. All observed effects were maintained 2-weeks after the intervention period.

CONCLUSION: The observed relationships suggest that naproxen may benefit highly lonely individuals with concurrent elevated levels of perceived stress.