Title : Reduction in mood and behavioural variability precedes functional recovery in patients with addiction: A 25-year longitudinal naturalistic study

Background: Substance use disorders are characterized by impaired regulation of emotion, behaviour, cognitive and executive function. Functional neuroimaging studies consistently demonstrate abnormalities in frontostriatal and limbic networks that parallel these clinical features. We hypothesized that reducing mood and behavioural variability represents an important early step in successful addiction treatment.

Methods: We performed a retrospective longitudinal analysis of de-identified electronic medical records collected during routine outpatient psychiatric and addiction practice over a 25-year period. The database comprised more than 92,000 follow-up records reorganized into approximately 34,800 medication and narrative events involving 2,136 patients. Structured medication records and longitudinal clinical narratives were reviewed to identify addictionrelated symptoms, mood-stabilizer exposure and subsequent changes in emotional regulation, impulsivity, compulsive behaviours, substance use and functional recovery.

Results: Addiction or compulsive-behaviour signals were identified in 1,783 patients, mood-stabilizer exposure in 886, and both in 828. These medications included: Lamotrigine, Topiramate, Valproate and Aripiprazole. A higher-confidence longitudinal cohort comprised 205 patients, of whom 164 (80.0%) received Lamotrigine. Following mood-stabilizer exposure, 202 (98.5%) demonstrated improved overall functioning, 92 (44.9%) described reduced emotional reactivity or greater calmness, 77 (37.6%) reported improved executive control or cognitive clarity, and 22 (10.7%) documented reductions in craving, compulsive behaviours or relapserelated language. Clinical narratives also frequently described recurrence of emotional and behavioural instability following medication interruption or missed doses, often first recognized by family members.

Conclusions: In this longitudinal real-world cohort, mood stabilization was consistently associated with subsequent improvements in behavioural regulation and overall functioning among patients with addiction and co-occurring psychiatric disorders. These findings support the hypothesis that reducing mood and behavioural variability may represent an important treatmentsequencing step that facilitates engagement with psychotherapy, recovery programs and treatment of co-occurring psychiatric disorders. Prospective studies are warranted to determine whether stabilization-first strategies improve long-term addiction outcomes. 

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