Hypomanic symptoms and first manic episode during ketogenic diet treatment in a patient taking venlafaxine: a case report with longitudinal glucose-ketone index and clinical monitoring.

BACKGROUND: The ketogenic diet (KD) is gaining increasing interest as a metabolic intervention for neuropsychiatric disorders, including mood disorders. However, its potential role in clinically relevant affective changes, such as hypomania or mania, remains insufficiently characterized.

METHODS: We present the case of a woman with a previous history of major depressive episode with psychotic symptoms and a posterior history of recurrent episodes of mild depression, who never achieved complete symptom remission. In an effort to ameliorate her chronic depressive symptoms, the patient started a KD for approximately 6 months. Metabolic monitoring included daily capillary measurements of glucose and ketone levels, with calculation of the glucose-ketone index (GKI) to assess ketosis and dietary adherence. Anthropometric parameters and physiological variables were recorded longitudinally. Laboratory assessments were performed before, during, and after the intervention. Psychiatric outcomes were evaluated using clinical scales, including the YMRS, PANSS, CGI, GAF, WHODAS and OAS, allowing assessment of symptom severity and clinical evolution. Pharmacologic, dietary, substance-related, sleep-related, and psychosocial exposures were reconstructed across clinically relevant phases.

RESULTS: After KD initiation, the patient reported improved mood and vitality, increased energy, reduced need for sleep, slight euphoria, and increased goal-directed activity. This period was retrospectively interpreted as possible hypomania. Four months after KD initiation, in the context of ongoing venlafaxine treatment (112.5 mg/day), absence of mood-stabilizing treatment, psychosocial stressors, reduced sleep and increased alcohol intake, and possible dietary drift, she developed a manic episode with psychotic features requiring urgent psychiatric care and home hospitalization. Symptoms remitted after antipsychotic treatment, lithium initiation, venlafaxine dose reduction, and temporary KD interruption. After remission, the patient chose to restart a less intensive KD under close supervision.

CONCLUSION: This case describes hypomanic symptoms and subsequent mania temporally associated with KD in a patient taking venlafaxine with prior antidepressant-associated hypomanic symptoms and later diagnostic reclassification to bipolar I disorder. To our knowledge, it is the first report providing a longitudinal characterization of metabolic parameters in relation to the clinical course of mania. The case highlights the need to monitor mood, sleep, alcohol use, antidepressant exposure, dietary adherence, and ketosis when KD is considered in mood-disorder populations.