Research paperAnhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials

- Ketamine has been associated with rapid reductions in suicidal thoughts.
- Ketamine has also been associated with reductions in anhedonia.
- Ketamine's anti-suicidal effects may be due to its ability to reduce anhedonia.
- Anhedonia may be an important research and treatment target for suicidal thoughts.

BackgroundIdentifying clinical correlates associated with reduced suicidal ideation may highlight new avenues for the treatment of suicidal thoughts. Anhedonia occurs across psychiatric diagnoses and has been associated with specific neural circuits in response to rapid-acting treatments, such as ketamine. This analysis sought to evaluate whether reductions in suicidal ideation after ketamine administration were related to reduced levels of anhedonia, independent of depressive symptoms.MethodsThis post-hoc analysis included treatment-resistant patients with either major depressive disorder (MDD) or bipolar disorder (BD) from several clinical trials of ketamine. Anhedonia was assessed using a subscale of the Beck Depression Inventory (BDI) and the Snaith-Hamilton Pleasure Scale (SHAPS). The outcome of interest was suicidal ideation, as measured by a subscale of the Scale for Suicide Ideation (SSI5), one day post-ketamine administration.ResultsAnhedonia, as measured by the SHAPS, was associated with suicidal thoughts independent of depressive symptoms both before and after ketamine administration. One day post-ketamine administration, improvements on the SHAPS accounted for an additional 13% of the variance in suicidal thought reduction, beyond the influence of depressive symptoms. The BDI anhedonia subscale was not significantly associated with suicidal thoughts after adjusting for depressive symptoms.LimitationsData were limited to patients experiencing a major depressive episode and may not be generalizable to patients experiencing an active suicidal crisis.ConclusionsSuicidal thoughts may be related to symptoms of anhedonia independent of other depressive symptoms. These results have implications for the potential mechanisms of action of ketamine on suicidal thoughts.