Investigation of the efficiency of various antidepressant replacement regimens in the development of ssri-induced apathy syndrome

Abstract

Selective serotonin reuptake inhibitors (SSRI)-induced apathy syndrome occurs in 5–20% of patients taking these drugs. Objective: to investigate the possibility and advantages of switching patients with SSRI-induced apathy to treatment with a SSRI and norepinephrine reuptake inhibitor. Patients and methods. The investigation enrolled 105 depressive patients without psychotic symptoms, who were observed to develop symptoms of SSRI-induced apathy during SSRI antidepressant monotherapy for at least 6 months. The patients were randomized to groups: 1) 35 patients were switched to milnacipran (Ixel 50–100 mg/day) with simultaneous antidepressant replacement; 2) 35 patients were prescribed milnacipran with a 2-week gradual discontinuation of the previous SSRI; 3) 35 patients were switched to combined therapy with milnacipran 50–100 mg/day and sulpiride (Eglonyl 50 mg/day). The latter was prescribed to test the hypothesis for the benefits of combined correction of SSRI-induced apathy syndrome. The duration of the investigation was 3 months. Changes in the condition of the patients were assessed during their visits before and 1, 2, 4, 8, and 12 weeks after changing therapy. The efficiency of antidepressant therapy was studied using the 21-item Hamilton Depression Rating Scale (HDRS-21) and the Clinical Global Impression (CGI) rating scale; the changes in the severity of asthenic manifestations were examined according to a subjective asthenia assessment (Multidimensional Fatigue Inventory (MFI-20)). The UKU side effect rating scale was used to verify side effects. Results and discussion. A significant (p<0.05) pronounced thymoleptic effect of various treatment regimens (simultaneous and gradual replacement with monnacipran monotherapy, as well as a milnacipran-sulpiride combination) was confirmed at week 4 of treatment. There was a reduction in SSRI-induced apathy syndrome when switching to treatment with milnacipran or milnacipran-sulpiride in 71.4–80% of patients. Different therapy replacement regimens showed varying changes in the reduction of heterogeneous asthenoapathic symptoms. A favorable safety profile was established for both monotherapy with milnacipran and its combination with sulpiride. Conclusion. The antidepressant milnacipran (up to 100 mg/day) exhibits a high efficacy and a good tolerance in case of SSRI-induced apathy syndrome, as well as by a pronounced thymoleptic effect, including when combined with the antipsychotic sulpiride (50 mg/day).