Sustained Hematological Stability During Clozapine Rechallenge With Adjunctive Lithium: A Case Report of 15-Month Follow-Up

Clozapine is the most effective treatment for treatment-resistant schizophrenia, offering significant therapeutic benefits for patients who have failed to respond to other antipsychotic regimens. However, its clinical use is limited by the risk of severe hematological adverse events, particularly neutropenia and agranulocytosis. Lithium has been reported to induce leukocytosis through the stimulation of granulopoiesis and has been considered as a potential adjunctive strategy in the management of clozapine-associated neutropenia. However, long-term hematological outcomes of combined clozapine-lithium therapy remain insufficiently documented, particularly at subtherapeutic lithium levels. We report the case of a 32-year-old man with treatment-resistant schizophrenia and a prior history of clozapine-induced neutropenia. Following multiple antipsychotic treatment failures, clozapine was reintroduced and combined with low-dose adjunctive lithium (400 mg/day). Hematological and biochemical monitoring was conducted over a 15-month period, during which 25 sequential complete blood counts were analyzed. The mean leukocyte count was 9.23 ± 1.68 × 10³/mm³ (range: 5.55-13.07 × 10³/mm³), and the mean neutrophil count was 5.81 ± 1.49 × 10³/mm³ (range: 2.53-8.86 × 10³/mm³). No episodes of neutropenia were observed during follow-up. A strong positive correlation was found between total leukocyte and absolute neutrophil counts (r = 0.97; p < 0.001). Linear regression analysis showed no significant temporal decline in leukocyte levels (p = 0.846). Lithium plasma levels remained between 0.17 and 0.54 mmol/L, below the standard therapeutic range for mood stabilization. The patient showed clinical improvement and maintained global functioning without further psychiatric hospitalizations. This case suggests a possible role of adjunctive lithium in supporting hematological stability during clozapine therapy. Subtherapeutic lithium levels may be associated with stable leukocyte and neutrophil counts in selected cases; however, no causal relationship can be established. This approach should be considered exploratory and requires strict hematological monitoring.