Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

Background: Adolescent treatment resistant depression (TRD) is increasing in recent years. While ketamine showed rapid antidepressant effects in adult TRD studies, research on its effectiveness in adolescents is limited. Methods: This study examines the effects of intravenous ketamine vs. midazolam on depressive and anxiety symptomatology assessed by the Montgomery–Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Children’s Depression Inventory (CDI) at two time points—2 h after initial infusion (T0+2h) and 24 h after the end of the treatment (Te+24h) in a sample of 55 adolescent TRD females (27 receiving ketamine, 28 midazolam). Results: At T0+2h, within-group comparisons revealed a significant reduction in MADRS and HAM-A scores compared to baseline in the ketamine and midazolam groups. At Te+24h, both groups demonstrated similar significant reductions in MADRS, HAM-A, and CDI scores compared to baseline. The MADRS assessment in the ketamine group showed 33% and 59% responders, and in the midazolam group, 14% and 46% responders at T0+2h and Te+24h, respectively. HAM-A evaluation in the ketamine group revealed 33% and 56% responders, and in the midazolam group, 11% and 39% responders at T0+2h and at Te+24h, respectively. CDI rating discovered 11% and 44% responders in the ketamine group and 4% and 21% responders in the midazolam group at T0+2h and Te+24h, respectively. Moreover, inner tension significantly decreased in ketamine compared to the midazolam group at Te+24h. Conclusions: Ketamine showed a reduction in depressive and anxiety symptoms during a short-term period with particular efficacy in alleviating inner tension over midazolam, suggesting its potential advantages in specific symptom relief in rarely studied adolescent TRD.

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1–10, total score), and CDI (items A–E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD.

Autonomic nervous system (ANS) abnormalities are associated with major depressive disorder (MDD) already at adolescent age. The majority of studies so far evaluated parasympathetic and sympathetic branches of ANS individually, although composite indices including cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) seem to measure ANS functioning more comprehensively and thus could provide better psychopathologies’ predictors. We aimed to study CAB and CAR derived from high-frequency bands of heart rate variability and left ventricular ejection time during complex stress response (rest–Go/NoGo task–recovery) in MDD adolescents with respect to sex. We examined 85 MDD adolescents (52 girls, age: 15.7 ± 0.14 yrs.) and 80 age- and sex-matched controls. The MDD group showed significantly reduced CAB compared to controls at rest, in response to the Go/NoGo task, and in the recovery phase. Moreover, while depressed boys showed significantly lower CAB at rest and in response to the Go/NoGo task compared to control boys, depressed girls showed no significant differences in evaluated parameters compared to control girls. This study for the first time evaluated CAB and CAR indices in drug-naïve first-episode diagnosed MDD adolescents during complex stress responses, indicating an altered cardiac autonomic pattern (i.e., reciprocal sympathetic dominance associated with parasympathetic underactivity), which was predominant for depressed boys.

Background: Data on early changes in body composition during acute-phase treatment in adolescents with major depressive disorder (MDD) remain limited. In particular, the utility of novel anthropometric indices reflecting central and visceral adiposity has not been explored in this population. This study therefore aimed to examine short-term clinical outcomes alongside detailed anthropometric measures in drug-naïve adolescent inpatients receiving fluoxetine-based pharmacotherapy. Methods: Prospective, clinician-directed, non-randomized inpatient study. Drug-naïve adolescents with severe MDD (n = 23) received fluoxetine 20 mg/day, with some patients additionally receiving low-dose quetiapine (100 mg/day) based on clinical indication for six weeks. Depressive symptomatology was evaluated by questionnaires Montgomery–Åsberg Depression Rating Scale (MADRS) and Children’s Depression Inventory (CDI). Conventional and novel anthropometric indices (BMI, WHtR; BRI, AVI, ABSI, BAI) were examined using the objective bioimpedance-derived method for body composition. Results: Depressive symptom severity decreased over the six-week treatment period, with significant improvements observed on both MADRS and CDI (time effect p < 0.001). Response and remission rates increased over time in the overall sample. No statistically significant changes were observed in conventional or novel anthropometric indices across the study period. Conclusions: In this prospective pilot cohort of adolescent inpatients with MDD, six weeks of fluoxetine-based pharmacotherapy was associated with improvement in depressive symptoms. No short-term changes were observed in anthropometric indices; however, given the small sample size and limited follow-up, these findings should be interpreted cautiously and cannot be considered definitive evidence of cardiometabolic safety.