Synergistic Effect of Passiflora incarnata L., Herba and Cognitive Behavioural Therapy in the Management of Benzodiazepine Misuse

<b>Background/Objectives</b>. Chronic benzodiazepine (BDZ) use is frequently maintained beyond recommended durations due to neuroadaptation, psychological dependence, and withdrawal-related issues. <i>Passiflora incarnata</i> L., herba (<i>P. incarnata</i>) has shown anxiolytic and GABAergic activity that may mitigate withdrawal symptoms, while cognitive-behavioural therapy (CBT) targets maladaptive beliefs and behaviours sustaining BDZ misuse. This study investigates the independent and interactive effects of <i>P. incarnata</i> and CBT on BDZ dose reduction during a three-month tapering program. <b>Methods</b>. This retrospective observational study included 186 outpatients with anxiety or depressive disorders in clinical remission undergoing BDZ tapering, of whom 93 received a dry extract of <i>P. incarnata</i> as adjunctive treatment and 93, matched for diagnosis, age and sex, followed a standard tapering protocol. BDZ doses were assessed at baseline and three months. CBT was recorded as a binary variable based on the information documented in the medical records. An ANCOVA was performed to assess the impact of CBT and <i>P. incarnata</i> on BDZ reduction (change in mg diazepam equivalents), adjusting for sex, age, education, baseline anxiety and depression scores, initial BDZ and antidepressant dosage. A subgroup analysis was conducted to investigate the role of <i>P. incarnata</i> dosage in BDZ reduction. <b>Results</b>. Both CBT and <i>P. incarnata</i> were associated with significantly greater reductions in BDZ dosage at three months (CBT: <i>p</i> = 0.005, effect size: 0.032; <i>P. incarnata</i>: <i>p</i> < 0.001, effect size: 0.128). A significant interaction between CBT and <i>P. incarnata</i> was also observed (<i>p</i> = 0.037, effect size: 0.018), indicating a synergistic effect when both interventions were combined. Baseline sociodemographic characteristics, BDZ and antidepressant dosage and symptom severity did not differ significantly between groups. Patients taking 400-600 mg of <i>P. incarnata</i> dry extract showed a higher BDZ reduction compared to those taking 200 mg. <b>Conclusions</b>. These findings suggest that <i>P. incarnata</i> and CBT exert independent yet complementary effects in supporting BDZ tapering. Their combination appears to enhance dose reduction beyond either intervention alone, supporting a multimodal approach that addresses both neurobiological and psychological components of BDZ addiction. Prospective controlled studies are needed to confirm these results and to clarify their impact on long-term discontinuation outcomes.