¹Linkou Chang Gung Memorial Hospital, Psychiatry, Taoyuan, Taiwan, ²Taipei City Hospital and Psychiatric Center, Psychiatry, Taipei, Taiwan

Background: Anxiety disorders and psychosomatic conditions are conventionally managed with benzodiazepines (BZDs) or antidepressants. While effective, BZDs carry risks of dependence, and standard-dose selective serotonin reuptake inhibitors (SSRIs) are often limited by poor tolerability. In many clinical settings, combination psychotropics—most notably flupentixol/melitracen (Deanxit)—have been widely utilized as an alternative. However, concerns regarding the long-term safety of its older components, potential extrapyramidal side effects, and lack of modern regulatory approval in certain jurisdictions persist. There is a clear clinical need for a modern, safer non-benzodiazepine alternative.

Aims & Objectives: This study proposes a novel pharmacological strategy combining very low-dose aripiprazole (1 mg) with low-dose escitalopram (2 mg). The objective is to provide a superior alternative to both BZDs and Deanxit, achieving potent anxiolysis through the synergistic modulation of dopamine and serotonin systems while maintaining a cleaner safety profile.

Method: The formulation utilizes a fraction of the defined daily doses (DDD) of modern psychiatric agents. We analyze the neurobiological synergy between aripiprazole’s dopamine-stabilizing properties (D2 partial agonism) and escitalopram’s selective serotonin reuptake inhibition. The hypothesis is that this "micro-dose" dual-mechanism approach achieves therapeutic efficacy comparable to Deanxit but with reduced risk of metabolic, extrapyramidal, or cardiovascular adverse effects.

Results: Theoretical analysis and clinical observations suggest: 1. Targeted Anxiolysis: Effectively addresses psychosomatic symptoms and psychic anxiety without the sedation of BZDs or the "old-generation" risks of Deanxit. 2. Improved Tolerability: Using only 2 mg of escitalopram avoids common SSRI-induced apathy, while 1 mg of aripiprazole remains well below the threshold for motor side effects. 3.No Abuse Liability: Provides a sustainable long-term solution without the addiction traps associated with BZDs. 4. Clean Pharmacokinetics: Minimal metabolic load and drug-drug interactions compared to older tricyclic-based combinations. (Table 1).
Table 1 Comparison of current medications for anxiety disorders and proposed medication (aripiprazole-escitalopram)

Feature	BZDs	SSRIs	SGAs	Flupentixol-Melitracen	Aripiprazole-Escitalopram
Primary Mechanism	GABAA Modulation	5-HT Reuptake Inhibition	D2 Antagonism	D2 Antagonism / NE & 5-HT Reuptake Inhibition	D2 Partial Agonism / SSRI
Abuse Potential	High	None	Low	Low	Negligible
Risk of EPS	None	Very mild	Moderate (Dose-dependent)	Mild (Dose-dependent)	Minimal (Subclinical dose)
Metabolic Risk	Low	Mild	Moderate	Low–Moderate	Minimal
Other Side Effects	Sedation	Sexual Dysfunction	Tardive Dyskinesia	Anticholinergic effects	Minimal
Major Indication	Acute Anxiety	Major Depression	Schizophrenia	Anxiety, Psychosomatic Disorders	Anxiety Disorders Psychosomatic Disorders

Abbreviation: BZD, benzodiazepine; SSRI, selective serotonin reuptake inhibitor; SGA, second generation antipsychotic; GABAA, γ-aminobutyric acid A, 5HT, 5-hydroxytryptamine (serotonin); D2, dopamine receptor 2; NE, Norepinephrine; EPS, extrapyramidal syndrome

Discussion & Conclusions: "Synergistic Modulation of Monoamine Circuitry" represents a contemporary evolution in anxiety management. By replacing the outdated components of therapies like Deanxit with a precision micro-dose of modern stabilizers and enhancers, this strategy offers a safer, non-addictive, and better-tolerated paradigm. This non-benzodiazepine approach warrants systematic clinical evaluation to replace legacy treatments and improve long-term outcomes for patients with anxiety and psychosomatic disorders.