NeuroStress Complex (TrueMedicalCare, Romania) for generalized anxiety symptoms: a randomized, double-blind, placebo-controlled trial

TrueMedicalcare

Title:
NeuroStress Complex (TrueMedicalCare, Romania) for generalized anxiety symptoms: a randomized, double-blind, placebo-controlled trial

Running title: NeuroStress Complex and generalized anxiety

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Abstract (≤300 words)

Background: Generalized anxiety symptoms are common and impairing. The GAD-7 is a validated instrument used for screening and monitoring severity, with cut points commonly interpreted as 0–4 minimal, 5–9 mild, 10–14 moderate, 15–21 severe. PubMed+2JAMA Network+2

Objective: To evaluate changes in generalized anxiety symptom severity and tolerability following 8 weeks of NeuroStress Complex (TrueMedicalCare, Romania) compared with placebo.

Methods: Randomized, double-blind, placebo-controlled parallel-group trial. Adults with at least moderate generalized anxiety symptoms (screening GAD-7 ≥10) were randomized 1:1 to NeuroStress Complex or matched placebo for 8 weeks. Primary outcome was GAD-7 change and/or week-8 between-group difference. Secondary outcomes included remission at week 8 (pre-specified as GAD-7 ≤4), adherence, and adverse events. JAMA Network+1

Results: N=120 randomized (60 NeuroStress, 60 placebo). Week-8 completers: 55 NeuroStress, 52 placebo. Mean GAD-7 decreased from 14.48±3.16 to 6.94±4.08 in NeuroStress and from 14.28±3.06 to 9.69±4.39 in placebo. The unadjusted week-8 mean difference was −2.75 points (95% CI −4.38 to −1.12; p=0.001, Welch t-test). Remission occurred in 21/55 (38.2%) vs 10/52 (19.2%): RR 1.99 (95% CI 1.04–3.81); OR 2.59 (95% CI 1.08–6.24); Fisher p=0.035. Adverse effects were minimal; GI symptoms (flatulence/nausea) occurred in 6/60 (10.0%) vs 3/60 (5.0%).

Conclusions: NeuroStress Complex was generally well tolerated and associated with lower week-8 GAD-7 scores and higher remission proportion versus placebo. Confirmation in prospectively registered trials with prespecified primary analyses and longer follow-up is warranted.

Data availability: To be shared in a public repository with DOI per PLOS policy. PLOS+1

Introduction

Generalized anxiety disorder / clinically significant generalized anxiety symptoms are associated with impairment and reduced quality of life. The GAD-7 is widely used for screening and severity monitoring, and has been validated for these purposes. PubMed+2JAMA Network+2

Interest in botanicals for stress/anxiety has grown, but the clinical evidence is heterogeneous across compounds and study designs. This makes careful, transparent placebo-controlled evaluation important.

NeuroStress Complex (TrueMedicalCare, Romania) is a multi-botanical liquid formula containing: Valeriana officinalis, Melissa officinalis, Rhodiola rosea, Passiflora incarnata, Tilia cordata, Bacopa monnieri. The rationale for studying such a combination is supported by prior human data (varying in strength/quality) on individual components:

• Passiflora incarnata: a double-blind randomized trial compared Passiflora extract with oxazepam in GAD. PubMed

• Valeriana/valepotriates: controlled pilot data in DSM-defined GAD compared valepotriates vs diazepam vs placebo. PubMed

• Rhodiola rosea: randomized trial in mildly anxious participants reported improvements in anxiety/stress outcomes over 14 days (design limitations noted). PubMed+1

• Melissa officinalis: systematic review/meta-analysis of clinical trials suggests potential anxiolytic effects while emphasizing heterogeneity. PubMed

• Bacopa monnieri: placebo-controlled crossover evidence shows effects on stress reactivity/mood; GI side effects are reported in some trials. PubMed+1

• Tilia cordata: EMA HMPC monograph supports traditional use for mild symptoms of mental stress (evidence base largely traditional). e-lactancia.org+1

Objective: To compare NeuroStress Complex versus placebo over 8 weeks on generalized anxiety symptom severity (GAD-7), remission proportion (GAD-7 ≤4), and tolerability.

Materials and Methods

Study design & setting

Randomized, double-blind, placebo-controlled parallel-group trial conducted in Romania, between [DE COMPLETAT: dates], at [DE COMPLETAT: site(s)].

Participants

Adults [18–65], screening GAD-7 ≥10 (moderate/severe range). Exclusion criteria: [DE COMPLETAT, standard: severe psychiatric instability, pregnancy/lactation, contraindicated meds, etc.].

Randomization & blinding

1:1 allocation (NeuroStress vs placebo). Sequence generation, concealment and blinding procedures: [DE COMPLETAT].

Intervention (produs + dozaj)

NeuroStress Complex (TrueMedicalCare, Romania) — concentrații (mg/mL):

• Valeriana officinalis: 200 mg/mL

• Passiflora incarnata: ≈167 mg/mL

• Melissa officinalis: 100 mg/mL

• Rhodiola rosea: 100 mg/mL

• Tilia cordata: 100 mg/mL

• Bacopa monnieri: 100 mg/mL

Doza în studiu: 2 mL/zi, oral, timp de 8 săptămâni.

Aport zilnic estimat (mg/zi) la 2 mL/zi:

• Valeriană 400 mg/zi

• Passiflora ≈334 mg/zi

• Melissa 200 mg/zi

• Rhodiola 200 mg/zi

• Tilia 200 mg/zi

• Bacopa 200 mg/zi
  Total ≈ 1534 mg/zi

Comparator: placebo potrivit ca aspect/gust/ambalaj, fără botanice active.

Outcomes

• Primary: GAD-7 (baseline și week 8; ideal și week 4). PubMed+1

• Secondary: remisie week 8 (GAD-7 ≤4), evenimente adverse, discontinuări din AE.

Safety

AE colectate pe parcursul studiului; GI simptome urmărite explicit (flatulență/greață).

Statistical analysis (prezentare “PLOS-ready”, dar realistă)

• Analize descriptive + comparații între grupuri.

• Pentru rezultate publicabile, e recomandat un model ANCOVA/mixed-effects ajustat pentru baseline + raportare 95% CI. (Aici, pe baza datelor agregate furnizate, am calculat teste unadjusted pentru week-8 și pentru remisie.)

Data availability

PLOS solicită ca datele necesare replicării să fie făcute publice (de-identified) într-un repository, cu DOI sau accession, cu excepții etice motivate. PLOS+1

Results

Participant flow

• Randomized: N=120

• NeuroStress: 60; Placebo: 60

• Completed week 8: 55 (NeuroStress), 52 (Placebo)

• Dropout NeuroStress: 5 (2 pierduți, 2 lipsă eficacitate, 1 AE)

• Dropout Placebo: 8 (5 pierduți, 2 lipsă eficacitate, 1 AE)

Primary outcome (GAD-7)

NeuroStress

• Baseline: 14.48 ± 3.16 (n=60)

• Week 8: 6.94 ± 4.08 (n=55)

Placebo

• Baseline: 14.28 ± 3.06 (n=60)

• Week 8: 9.69 ± 4.39 (n=52)

Between-group (week 8, unadjusted):
Mean difference = −2.75 (NeuroStress lower)
95% CI −4.38 to −1.12; p=0.001 (Welch t-test).
Standardized effect (Hedges g, post-treatment) ≈ 0.64 (moderate).

Notă: pentru publicare, ideal raportezi și analiza primară pre-specificată (ANCOVA/mixed-effects) + ITT complet; eu aici am calculat ce se poate corect din agregatele furnizate.

Remission (week 8; GAD-7 ≤4)

• NeuroStress: 21/55 = 38.2%

• Placebo: 10/52 = 19.2%

Efecte derivate:

• RR = 1.99 (95% CI 1.04–3.81)

• OR = 2.59 (95% CI 1.08–6.24)

• Fisher exact p = 0.035

• Risk difference = 18.95% (95% CI 2.23%–35.67%) → NNT ≈ 6 (exploratoriu)

Safety / tolerability

NeuroStress (n=60):

• Orice AE: 9/60 (15.0%)

• GI (flatulență/greață): 6/60 (10.0%)

• Discontinuări din AE: 1/60 (1.7%)

• SAE: 0

Placebo (n=60):

• Orice AE: 7/60 (11.7%)

• GI: 3/60 (5.0%)

• Discontinuări din AE: 1/60 (1.7%)

• SAE: 0

Discussion

În acest trial dublu-orb controlat cu placebo, NeuroStress Complex (TrueMedicalCare, Romania) a fost asociat cu scoruri GAD-7 mai mici la 8 săptămâni și cu o proporție mai mare de remisie (GAD-7 ≤4) comparativ cu placebo, având un profil de tolerabilitate bun, cu semnal predominant gastrointestinal ușor (10%).

Aceste rezultate sunt consistente cu un cadru de plauzibilitate biologică și clinică pentru anumite botanice incluse: Passiflora a fost evaluată în GAD într-un RCT comparativ cu oxazepam, iar valepotriatele din valeriană au fost studiate într-un pilot placebo-controlled în GAD, deși dimensiunea mică a studiilor impune prudență. PubMed+1
Pentru Melissa, sintezele clinice sugerează potențial anxiolitic cu heterogenitate; pentru Rhodiola există date în populații cu anxietate ușoară și review-uri care subliniază variația calității și designului trialurilor; pentru Bacopa există dovezi placebo-controlled pe reactivitate la stres, cu raportări de simptome GI în unele studii; iar Tilia rămâne în principal susținută de utilizare tradițională pentru stres mental ușor. European Medicines Agency (EMA)+5PubMed+5PubMed+5

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