Nicotine and Caffeine Co-Use as a Compensatory Response to Early Antipsychotic-Induced Dysfunction: A Case-Based Mechanistic Report

Background: Early adverse effects of antipsychotics and SSRIs—such as hyperprolactinemia, affective blunting, cognitive slowing, and akathisia—impair tolerability and adherence. Fast, dose‑limited adjuncts that transiently counter early dopaminergic/cholinergic suppression may bridge the initiation phase without replacing standard care. Case: A young adult on paroxetine 20 mg/day, sulpiride 100 mg/day, and lamotrigine 100 mg/day experienced reproducible improvement in libido, urinary hesitancy, affective responsiveness, and cognitive focus within 30–60 minutes after self‑administered low‑to‑moderate nicotine (≈9 mg/day, pod inhalations) and caffeine (≈200–380 mg/day). Higher cumulative stimulation provoked a short post‑stimulant dysphoric/anxious state, underscoring the need for titration. Mechanistic interpretation: Nicotine (α4β2/α7-nAChR) enhances mesocorticolimbic dopaminergic tone and attentional control, while caffeine (A1/A2A antagonism) disinhibits D2 signaling in the indirect pathway; their convergence can transiently restore fronto-striatal throughput. Clinical implications: Brief, structured co-use under supervision may act as a pragmatic, falsifiable strategy to improve early tolerability, with pharmacovigilance (e.g., monitoring anxiety, sleep, blood pressure and heart rate) and predefined stopping rules. Conclusion: In this case, nicotine–caffeine co-use functioned as a rapid‑onset compensatory approach during early antipsychotic/SSRI therapy. Controlled n‑of‑1 microtrials could test efficacy and safety.