The fleeting nature of ketamine's life-saving effects against suicidal thoughts has long frustrated clinicians seeking durable interventions for patients in crisis. While ketamine can rapidly reduce suicidal ideation in major depression, these protective benefits typically fade within days, leaving vulnerable patients at renewed risk. A controlled trial of 50 adults with major depression and significant suicidal ideation demonstrates that low-dose sublingual buprenorphine can meaningfully extend ketamine's protective window. Participants received a single ketamine infusion followed by either buprenorphine (0.2-0.8 mg daily) or placebo for four weeks. The buprenorphine group showed substantially greater reductions in suicidal thoughts, with mean improvements of 11.6 points versus 6.3 points on standardized scales—representing a large effect size of 0.76. This combination approach targets the mu-opioid receptor system, which emerging research suggests plays a crucial role in both ketamine's rapid antidepressant effects and suicidal ideation itself. The strategy represents a paradigm shift from treating ketamine as a standalone intervention toward viewing it as an initial catalyst requiring strategic follow-up maintenance. However, this single-center study's modest size and the inherent risks of opioid medications—even at these low doses—demand careful replication before clinical implementation. The findings could transform acute suicide prevention protocols, potentially offering weeks rather than days of protection for patients emerging from suicidal crises, though larger trials must first establish both efficacy and safety across diverse populations.