Changes in the enzymatic activity of antioxidant, energy and glutamate metabolism as predictors of the effectiveness and tolerability of therapy for late-life depression

Background: metabolic changes involved in the pathogenesis of late-life depression are associated not only with clinical heterogeneity of depressions, but also with responses to antidepressant therapy and its tolerability.

The Aim was to study of the possibility of using models of enzymatic activity of energy, antioxidant and glutamate metabolism in late-life depression as additional biochemical predictors of the effectiveness and tolerability of antidepressant therapy.

Patients and Methods: 50 hospitalized patients aged ≥ 60 years with a depressive episode of different diagnostic categories according to ICD-10 (F33.0–F33.3; F31.3–F31.4; F32.0–F32.2) who received 28-day antidepressant therapy were examined using clinical, psychometric and biochemical methods. The effectiveness and tolerability of therapy were compared in patients with “reduced” antioxidant and energy metabolism (44.2% of cases), with “multidirectional” enzymatic activity with reduced antioxidant, increased energy and glutamate metabolism (21.2%), and with “normal” metabolism (34.6%). The efficacy criteria were: response rate (50% reduction in baseline HAMD-17 score), change in mean HAMD-17 total score, and complete remission rate (≤ 7 points on HAMD17). Tolerability was assessed by the number, types and severity of side effects. Statistical analysis was performed using the Mann-Whitney U test and the χ² coefficient.

Results: all patients with “normal” enzymatic activity were responders with a low incidence of side effects (25% of cases). Patients with “reduced” metabolism had a high frequency of acute side effects (73.9%, p < 0.01), while patients with “multidirectional” metabolism had a low degree of response to therapy (63.6%, p < 0.01). Patients in the last two groups are recommended additional therapy with antioxidants and neurometabolic drugs with stimulating or balancing action. Patients with “multidirectional” metabolism are also indicated for GABA-ergic drugs or “fast” glutamatergic antidepressants.

Conclusion: models of enzymatic activity of antioxidant, energy and glutamate metabolism may, along with clinical characteristics, be additional predictors of the effectiveness and tolerability of antidepressant therapy. Their definition can be the basis for personalized indications for the administration of different types of adjuvants neurometabolic therapy in
elderly depressive patients.

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