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REVIEW ARTICLE

# Mechanisms, clinical implications, and treatment strategies for autonomic health dysfunction in anxiety and depression

Majedul HOQUE

## ABSTRACT

Disturbances in emotion regulation and physiological homeostasis characterize anxiety and depression, two of the most common mental health disorders worldwide. Emerging research implicates autonomic nervous system (ANS) dysfunction—specifically an imbalance between sympathetic and parasympathetic activity—in their pathogenesis. Patients with anxiety and depression exhibit altered heart rate variability, impaired baroreflex sensitivity, and disrupted hypothalamic-pituitary-adrenal (HPA) axis interactions, indicative of compromised autonomic regulation. This review highlights diverse autonomic disorders and etiologies associated with these conditions, critically explores the neurobiological mechanisms linking the ANS to affective disorders, and discusses potential therapeutic approaches aimed at restoring autonomic balance.

**Keywords:** Autonomic nervous system, depression, autonomic disorder, HRV, MSA.

Department of Pharmacy, Jahangirnagar University, Dhaka-1342, Bangladesh.

**Received:** 02 Nov 2025

**Accepted:** 22 Nov 2025

Correspondance to: Majedul HOQUE

E-mail: majed.pharmju44@gmail.com

## 1. INTRODUCTION

The autonomic nervous system (ANS) controls involuntary physiological functions including digestion, blood pressure, heart rate, and sexual desire. It belongs to the peripheral nervous system as a subcomponent. The enteric, parasympathetic, and sympathetic nervous systems are all a part of the autonomic nervous system. Afferent and efferent fibers found in the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) supply the central nervous system (CNS) with motor output and sensory input [1]. The basic activity levels of the parasympathetic and sympathetic nervous systems are known as sympathetic and parasympathetic tonus, and they are both always active. The former is found in the systemic arterioles, and the latter is found in the intestines. The heart's sympathetic activity rises with effort, but parasympathetic activity (parasympathetic tone) prevails at rest [2].

Two of the most common mental illnesses in the world are anxiety and depression, which frequently coexist and significantly increase the burden of disease worldwide. In addition to their significant psychological effects, these diseases are becoming more widely acknowledged as systemic conditions involving dysregulation of the autonomic nerve system (ANS), a vital network that controls metabolic, respiratory, and cardiovascular processes to maintain homeostasis. People with anxiety and depression have been shown to have autonomic dysfunction, which is defined by an imbalance between sympathetic and parasympathetic activity. This suggests that their emotional and physical symptoms have a physiological basis [3, 4].

There has been increasing evidence that the relationship between mood disorders and autonomic instability is mediated by neuroinflammation, chronic stress, and changes in the hypothalamic-pituitary-adrenal (HPA) axis. Common results include muted parasympathetic activity, elevated sympathetic tone, and decreased heart rate variability (HRV), which indicate a decreased capacity to adjust to both internal and external stimuli. The clinical significance of comprehending ANS abnormalities in these situations is highlighted by the fact that these disruptions not only worsen psychological symptoms but also raise the risk of cardiovascular morbidity and mortality [5-7].
From a therapeutic perspective, autonomic regulation-focused interventions—like medication, biofeedback, mindfulness exercises, and neuromodulation—offer encouraging paths toward comprehensive care. More accurate, mechanistically based approaches to treating anxiety and depression may result from investigating the reciprocal link between emotional regulation and autonomic function [8, 9]. The purpose of this article is to investigate the mechanism behind autonomic dysfunction in depression and anxiety, talk about its clinical implications, and look at novel therapeutic approaches that attempt to restore autonomic balance and enhance general mental and physical health outcomes.

## 2. POSSIBLE MECHANISMS OF HOW THE ANS IS LINKED TO ANXIETY AND DEPRESSION

In healthy individuals, the parasympathetic nervous system (PNS), mostly controlled by the vagus nerve, helps with rest and recovery. In contrast, the sympathetic nervous system (SNS) drives arousal and stress responses. A hyperactive SNS and an underactive PNS are often found in cases of anxiety and depression. This imbalance, which shows a lack of autonomic flexibility, leads to increased physiological arousal, a higher heart rate, and lower heart rate variability (HRV). Reduced vagal activity makes it harder to regulate emotions and cope with stress. Meanwhile, ongoing sympathetic dominance increases the perception of stress and extends symptoms of anxiety [10-12].

The ANS and the hypothalamic pituitary adrenal (HPA) axis work together closely during stress responses. Long-term activation of the HPA axis, which raises cortisol levels and impairs negative feedback mechanisms, is caused by emotional dysregulation in anxiety and depression and chronic psychological stress. Structures of the limbic system, including the hippocampus, amygdala, and prefrontal cortex—areas crucial for mood regulation and autonomic control—are altered by elevated glucocorticoid release. The result of this dysregulation is a feedback loop that sustains physiological hyperarousal and emotional discomfort by reinforcing sympathetic overactivity and suppressing parasympathetic tone [13, 14].

There is increasing evidence that neuroinflammation plays a significant role in emotional and autonomic disorders. Patients with anxiety and depression have been shown to have higher levels of pro-inflammatory cytokines, including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). These cytokines change vagal transmission and disrupt the metabolism of neurotransmitters, particularly dopamine and serotonin. Normally, the vagus nerve helps reduce inflammation through the cholinergic anti-inflammatory pathway. However, when vagal activity decreases, unmanaged inflammation can worsen mood symptoms and further disrupt autonomic function [15, 16].

Stress sensitivity can be increased by reduced serotonin availability, which can also decrease parasympathetic tone and enhance sympathetic drive. Similarly, increased noradrenergic activity raises sympathetic arousal and is linked to signs of anxiety disorders, such as perspiration, tachycardia, and restlessness. The brainstem nuclei that coordinate central autonomic output, including the locus coeruleus and the dorsal motor nucleus of the vagus, are impacted when these neurotransmitters are dysregulated [17].

According to neuroimaging research, the brain areas in charge of autonomic regulation exhibit both structural and functional changes in response to anxiety and sadness. The central autonomic network (CAN), which integrates emotional and physiological responses, is made up of the prefrontal cortex, anterior cingulate cortex, amygdala, and insular cortex. The top-down regulation of the ANS is disrupted by amygdala hyperactivity and prefrontal cortex hypoactivity, which leads to sympathetic overdrive and decreased vagal control. Both physiological indicators of autonomic imbalance and emotional dysregulation are correlated with such patterns [18, 19].

Genetic predispositions that impact stress reactivity and ANS control may make people more susceptible to anxiety and depression. Differences in genes that encode glucocorticoid receptors, serotonin transporters (such as 5-HTTLPR), and catecholamine-metabolizing enzymes affect how people react emotionally and autonomically to stress. Furthermore, long-term stress can cause epigenetic changes like DNA methylation or histone acetylation that change the expression of genes linked to the HPA axis and autonomic regulation, hence keeping maladaptive stress reactions [20, 21].

The cardiovascular and metabolic systems are impacted by the autonomic imbalance that is present in anxiety and depression. Chronic sympathetic activation raises the risk of heart disease and hypertension by causing endothelial dysfunction, elevated blood pressure, and changed baroreflex sensitivity. The apparent comorbidity between mood disorders and metabolic syndrome is also influenced by autonomic dysfunction, which affects metabolic processes like insulin sensitivity and lipid control.

## 3. AUTONOMIC DISORDER

An essential part of the human nervous system, the autonomic nervous system regulates involuntary bodily processes like heart rate, blood pressure, digestion, temperature regulation, and respiration in addition to preserving internal physiological equilibrium [22]. It
maintains homeostasis and reacts appropriately to changes in the environment by working automatically and without conscious thought. Autonomic disorder is the term used to describe the ailment that results from the ANS's malfunction [23]. A wide range of clinical symptoms affecting many organ systems can result from these disorders (Table 1), which can occur as primary conditions or as sequel conditions to other diseases.

<table><caption>**Table 1.** Major diseases and disorders of the autonomic nervous system.</caption><thead><tr><td>Disorder</td><td>Description</td><td>Primarily affected function</td><td>Common symptoms</td></tr></thead><tbody><tr><td>Autonomic Neuropathy</td><td>Damage to autonomic nerves regulating internal organs</td><td>Sympathetic and parasympathetic</td><td>Dizziness, fainting, abnormal sweating, GI issues, urinary problems</td></tr><tr><td>Postural Orthostatic Tachycardia Syndrome (POTS)</td><td>Abnormal heart rate increase upon standing</td><td>Sympathetic</td><td>Rapid heartbeat, dizziness, fatigue</td></tr><tr><td>Multiple System Atrophy (MSA)</td><td>Neurodegenerative disorder affecting autonomic and motor systems</td><td>Sympathetic and parasympathetic</td><td>Orthostatic hypotension, bladder dysfunction, motor problems</td></tr><tr><td>Riley-Day Syndrome (Familial Dysautonomia)</td><td>Genetic disorder affecting sensory and autonomic neurons</td><td>Sympathetic and parasympathetic</td><td>Lack of tears, blood pressure instability, GI problems</td></tr><tr><td>Baroreflex Failure</td><td>Impaired blood pressure regulation due to baroreceptor damage</td><td>Sympathetic</td><td>Extreme blood pressure fluctuations, headaches</td></tr><tr><td>Guillain-Barré Syndrome (Autonomic Variant)</td><td>Immune-mediated nerve inflammation</td><td>Both sympathetic and parasympathetic</td><td>Fluctuating blood pressure, arrhythmias, sweating problems</td></tr><tr><td>Diabetic Autonomic Neuropathy</td><td>Nerve damage from chronic diabetes</td><td>Sympathetic and parasympathetic</td><td>Sexual dysfunction, orthostatic hypotension</td></tr><tr><td>Horner's Syndrome</td><td>Damage to sympathetic pathway to the eye and face</td><td>Sympathetic</td><td>Ptosis, miosis, anhidrosis</td></tr></tbody></table>

## 4. REASONS FOR AUTONOMIC DYSFUNCTION

The peripheral autonomic nervous system is mediated by a number of commonly prescribed medications used to treat conditions that would otherwise appear to be unrelated, such as depression, hypertension, heart failure, asthma/airways disease, overactive bladder outlet obstruction, Alzheimer's-type dementia, and glaucoma. As a result, these medications may exacerbate or conceal autonomic dysfunction [24]. The progressive loss of autonomic neurons in pure autonomic failure (PAF), a degenerative disease, causes extensive autonomic failure, including severe orthostatic hypotension, urine incontinence, and decreased sweating. Alpha-synuclein buildup, a characteristic protein also shown in Parkinson's disease, is likely to be the cause, as it interferes with autonomic ganglia nerve signaling [25].

Multiple system atrophy is a neurological illness that causes extensive harm to the brainstem and basal ganglia, two areas that control movement and autonomic processes. Cerebellar ataxia, severe autonomic dysfunction, and parkinsonian symptoms are common presentations. Alpha-synuclein builds up abnormally in oligodendrocytes, which is the root reason and causes neuronal degeneration [26]. This condition, which is frequently brought on by mutations in the PHOX2B gene, impacts the brainstem regions that control respiration and autonomic reactions. During sleep, patients have poor breathing and reduced autonomic reactions to elevated carbon dioxide or low oxygen levels [27]. Autonomic dysreflexia is frequently linked to spinal cord injuries that occur above the T6 level. Unknown stimuli, such as a blocked urine catheter, fecal impaction, or pressure sores, can cause malignant hypertension to appear abruptly. The key to treating autonomic dysreflexia is identifying and controlling the triggering stimuli.

The most common cause of secondary autonomic dysfunction is diabetes. Diabetic autonomic neuropathy is caused by long-term hyperglycemia that affects peripheral nerves and tiny blood vessels. Orthostatic hypotension, resting tachycardia, decreased sweating, gastroparesis, and bladder dysfunction are typical symptoms. The length of the illness and inadequate glycemic management are major risk factors [28]. Some bacterial or viral infections can cause immune-mediated nerve damage or directly harm autonomic fibers. Notable instances include post-viral dysautonomia following infections with the Epstein-Barr virus, Lyme disease, or COVID-19, and
Guillain-Barré syndrome (GBS), particularly its subtype acute autonomic neuropathy. A growing number of post-COVID complications have been recorded, including postural orthostatic tachycardia syndrome (POTS) [29, 30].

Degeneration of the brain's autonomic centers and peripheral autonomic neurons is a common feature of conditions like Parkinson's disease, Alzheimer's disease, and Lewy body dementia. For example, autonomic symptoms including constipation, urine retention, and orthostatic hypotension may manifest before motor symptoms in Parkinson's disease [31, 32]. Peripheral and autonomic neuropathy can result from deficiencies in vitamins necessary for nerve function, including thiamine (B1), niacin (B3), and vitamin B12. Common underlying causes include malabsorption syndromes, prolonged alcoholism, and malnutrition [33]. Functional autonomic imbalance has a substantial correlation with depression, anxiety, and long-term stress. Prolonged sympathetic nervous system activation and parasympathetic activity suppression can cause hypertension, gastrointestinal disorders, and an accelerated heartbeat. These functional changes could eventually result in biochemical and structural modifications in autonomic circuits.

Autonomic nerves may be unintentionally harmed by some medical procedures. Radiation therapy, pelvic procedures, and neck or thoracic surgery, for instance, might cause sympathetic or parasympathetic fiber damage, which can result in regional autonomic dysfunction. Similar to this, nerve severing during organ transplant procedures can change autonomic reflexes.

## 5. AUTONOMIC DYSFUNCTION AND DEPRESSION

The sympathetic nervous system is more active when a person is under stress or is in a situation that is upsetting to them. In cases of mild depression, the sympathetic nervous system is engaged, whereas in cases of severe depression, the parasympathetic nervous system is active [34]. Changes in mood are frequently accompanied by autonomic changes. Decreases in heart rate variability (HRV) indices reflect changes in autonomic nervous system function that encourage vagal withdrawal. Decreased HRV is associated with prefrontal brain hypoactivity and is characterized by emotional dysregulation, diminished psychological flexibility, and impaired social interaction. The notion that HRV might serve as a helpful endophenotype for psychological and physical disorders is supported by this data [35].

A model of neurovisceral integration in relation to emotion regulation and dysregulation was presented by Thayer and Lane [36]. The authors assert that the ability to control one's emotions has significant health consequences. In circumstances where emotional control is necessary, HRV is a useful tool. According to the authors, people with greater baseline HRV levels exhibited context-appropriate emotional reactions; additionally, phasic activations in HRV in response to emotional change-requiring conditions have made successful emotional regulation easier [36].

Depression and autonomic dysfunction are related because they influence emotional and physiological reactions. The parasympathetic nervous system (PNS), which is mostly mediated by the vagus nerve, controls "rest and digest" processes, whereas the sympathetic nervous system (SNS) controls the body's "fight or flight" responses. Parasympathetic (vagal) tone falls and sympathetic activity becomes hyperactive in depression, which frequently upsets this equilibrium [35, 37]. Because of this imbalance, the body becomes autonomically stiff, making it less able to adjust to stress and environmental demands. Less HRV, which is a common indicator of reduced parasympathetic activity, is one of the most reliable biological indicators found in mania patients.

Serotonin, norepinephrine, and dopamine are monoamines that play a key role in mood control and autonomic functions. For example, lower vagal tone is connected to reduced serotonin levels. On the other hand, higher norepinephrine leads to tachycardia, anxiety, and restlessness, boosting sympathetic activity. The emotional and physical signs of depression arise from these neurotransmitter issues [38]. Neuroimaging studies show that the central autonomic network, which includes the prefrontal cortex, anterior cingulate cortex, amygdala, insula, and hypothalamus, is disrupted in depression. In depressed individuals, the autonomic nervous system is poorly regulated from the top down. This occurs because of hyperactivity in the amygdala and reduced activity in the prefrontal brain, which strengthens sympathetic dominance. Symptoms include increased heart rate, sleep disturbances, and impaired emotional regulation [39, 40].

## 6. AUTONOMIC FUNCTION IN EMOTION PROCESSING

The term "emotion regulation" describes how people alter, sustain, or manage their feelings, including how they manifest, experience, and react physiologically [41]. This involves a variety of techniques for controlling emotional experiences and their effects on behavior and thought processes, including expressive suppression, cognitive reappraisal, and attentional deployment. Emotional regulation can be maladaptive, which leads to interpersonal problems and psychopathology, or adaptive, which supports psychological welfare and social functioning. Emotional processing, on the other hand, describes the mental and emotional processes that go into evaluating, interpreting, and reacting to emotional inputs [42]. Perceptual, attentional, and memory functions are all included, along with higher-
order cognitive functions including problem-solving and cognitive reappraisal. Individual variations in emotion regulation and dysregulation, as well as social and cultural influences, can all have an impact on emotional processing.

Numerous physiological functions, such as emotion processing, communication, and regulation, are known to be influenced by the vagus nerve, a sophisticated network of nerve fibers that starts in the brainstem and runs throughout the body [43]. It appears that several vagal control systems are behaviorally related to social communication, mobilization, and immobilization and are phylogenetically ordered [43]. When emotional information is encoded or retrieved, the ANS may be activated, which could alter the neural mechanisms underlying mood-congruent memory [44]. At the nerve system level, the brain and ANS simultaneously regulate all peripheral systems, affect mood states, and regulate emotional processing and regulation [45, 46]. Emotions have been functionally associated with the brain's ability to predict bodily states. Ascending body or interoceptive signals, such as those sent by the vagus nerve, are continuously compared to the predictions [47].

## 7. CLINICAL IMPLICATIONS OF AUTONOMIC DYSFUNCTION

The effects of autonomic dysfunction on the cardiovascular system are among the most serious. By carefully balancing sympathetic and parasympathetic activity, the ANS typically keeps proper blood pressure and heart rate. This equilibrium is upset in autonomic dysfunction, resulting in orthostatic hypotension, a condition in which standing causes a large drop in blood pressure, which can cause fatigue, dizziness, and fainting. Postural orthostatic tachycardia syndrome (POTS), which causes palpitations and weakness when standing, is a condition that certain patients may have [48].

The central nervous system and autonomic dysfunction are closely related, and disruptions in the former frequently show up as neurological and psychiatric symptoms (Table 2). Autonomic dysfunction frequently precedes the onset of motor or sensory symptoms in illnesses including Parkinson's disease, multiple system atrophy (MSA), and diabetic neuropathy [49]. Implications for psychiatry are very important. Anxiety, sadness, and panic disorders are closely tied to disruptions in the autonomic nervous system, which regulates emotions and stress responses. Physiological arousal can increase when there is lower parasympathetic tone and higher sympathetic activity. This can result in emotional instability and chronic stress. Furthermore, problems with the autonomic system can affect attention, memory, and decision-making by reducing blood flow to the brain, which can lead to cognitive decline.

<table><caption>**Table 2.** Clinical implications of autonomic dysfunction in anxiety and depression.</caption><thead><tr><td>System affected</td><td>Clinical manifestation</td><td>Underlying autonomic reason</td></tr></thead><tbody><tr><td>Cardiovascular System</td><td>Elevated heart rate, increased blood pressure variability, palpitations</td><td>Sympathetic overactivity and reduced vagal tone</td></tr><tr><td>Respiratory System</td><td>Rapid or shallow breathing, dyspnea, hyperventilation</td><td>Autonomic imbalance affecting respiratory rhythm</td></tr><tr><td>Neuroendocrine/Metabolic</td><td>Increased cortisol, impaired glucose tolerance</td><td>Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and sympathetic drive</td></tr><tr><td>Sleep regulation</td><td>Insomnia, poor sleep quality, frequent awakenings</td><td>Reduced parasympathetic activity during sleep, elevated sympathetic tone</td></tr><tr><td>Cognitive/Emotional Regulation</td><td>Impaired concentration, emotional instability</td><td>Autonomic dysregulation impacting the limbic system</td></tr><tr><td>Gastrointestinal System</td><td>Nausea, abdominal discomfort, irritable bowel symptoms</td><td>Altered gut-brain axis and vagal dysfunction</td></tr><tr><td>Thermoregulatory System</td><td>Sweating, cold extremities, heat intolerance</td><td>Increased sympathetic activity</td></tr></tbody></table>

Autonomic regulation is important for the movement and secretion in the gastrointestinal tract. Gastroparesis is a condition characterized by slow stomach emptying. It can lead to bloating, nausea, and vomiting, and it can be triggered by autonomic dysfunction. Constipation, diarrhea, or changes in bowel habits are also common symptoms of Parkinson's disease and diabetic autonomic neuropathy [50, 51]. Autonomic regulation also affects the urogenital system. Significant discomfort and social misery can result from nocturia, incontinence, and urine retention caused by dysautonomia. Another big worry is sexual dysfunction; women may have trouble getting an orgasm or have decreased vaginal lubrication, while males may have erectile dysfunction [52]. Autonomic abnormalities are often associated with thermoregulation issues. Hyperhidrosis, or excessive perspiration, can cause discomfort and social embarrassment, whereas anhidrosis, or decreased perspiration, can lead to heat intolerance. These problems with temperature regulation demonstrate how much homeostasis can be upset by autonomic dysfunction [53].
The control of sleep-wake cycles is impacted by autonomic instability, which can lead to non-restorative sleep, excessive daytime drowsiness, and insomnia. People with autonomic dysfunction frequently experience chronic weariness and poor sleep, which exacerbates the consequences of other illnesses. Pain, psychological stress, and physical limitation all work together to drastically reduce everyday functioning and quality of life.

## 8. AUTONOMIC DYSFUNCTION TREATMENT

Autonomic dysfunction treatment requires a thorough, customized strategy that addresses the root cause as well as symptoms. While behavioral and lifestyle changes are essential for long-term maintenance, pharmaceutical treatments can normalize blood pressure, heart rate, and other autonomic processes [54, 55]. The goals of treating autonomic dysfunction include symptom management, underlying cause correction, and quality of life enhancement. It frequently calls for a multidisciplinary strategy that includes physical rehabilitation, lifestyle modifications, and medication. While metoclopramide or domperidone enhance gastrointestinal motility, medications like fludrocortisone, midodrine, and beta-blockers aid with blood pressure and heart rate regulation. Major treatment approaches for autonomic dysfunction are listed in Table 3) [54-59]. Pharmacological treatment modalities for autonomic dysfunction are shown in Table 4. For those with autonomic dysfunction, early identification and integrated care are crucial to avoiding problems, increasing functional ability, and improving overall quality of life.

<table><caption>**Table 3.** Key strategies for treating autonomic dysfunction.</caption><thead><tr><th>Category</th><th>Treatment type</th><th>Clinical effect</th><th>Examples of therapy</th></tr></thead><tbody><tr><td rowspan="10">Pharmacological</td><td>Beta-blocker</td><td>Lower heart rate, tremor, palpitations in anxiety</td><td>Propranolol, Atenolol</td></tr><tr><td>Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor.</td><td>Improve HRV, reduce sympathetic dominance in depression</td><td>Sertraline, Venlafaxine</td></tr><tr><td>Tricyclic antidepressants (TCAs)</td><td>Effective in depression with autonomic symptoms</td><td>Amitriptyline, Nortriptyline</td></tr><tr><td>Anxiolytics (benzodiazepines)</td><td>Decrease physiological arousal and anxiety</td><td>Alprazolam, Diazepam (short-term use)</td></tr><tr><td>Alpha-2 agonists</td><td>Stabilize blood pressure and pacify mentality</td><td>Clonidine, Guanfacine</td></tr><tr><td>Mineralocorticoids</td><td>Improve standing blood pressure, reduce dizziness</td><td>Fludrocortisone, Midodrine</td></tr><tr><td>Mindfulness & meditation</td><td>Lower cortisol, improve HRV, reduce anxiety</td><td>Mindfulness-Based Stress Reduction (MBSR) program</td></tr><tr><td>Yoga & Tai-chi</td><td>Improve HRV, balance ANS, lower blood pressure</td><td>Regular practice 3-4x/week</td></tr><tr><td>Aerobic exercise</td><td>Reduce resting heart rate, improve mood</td><td>Walking, cycling, swimming</td></tr><tr><td>Sleep Hygiene & Stress Management</td><td>Improve mood, cognitive clarity</td><td>Consistent sleep and relaxation technique</td></tr><tr><td rowspan="5">Behavioral</td><td>Adaptogens</td><td>Enhance resilience, restore ANS balance</td><td>Withania somnifera, Rhodiola rosea, Panax ginseng</td></tr><tr><td>Polyphenols</td><td>Support cardiovascular-autonomic health</td><td>Curcumin, Resveratrol, Green tea catechins</td></tr><tr><td>Omega-3 Fatty Acids</td><td>Reduce depressive and autonomic symptoms</td><td>Fish oil, Flaxseed oil</td></tr><tr><td>Group B vitamins and vitamin-D</td><td>Calm nervous system, lower stress reactivity</td><td>Food supplements and grains</td></tr><tr><td>Cognitive-Behavioral Therapy (CBT)</td><td>Enhances physiological regulation and tolerance</td><td>Gold standard for anxiety and depression</td></tr><tr><td rowspan="3">Nutritional/Phytomedicine</td><td>Hydration & Salt Intake</td><td>Prevents dizziness and fatigue</td><td>Useful in orthostatic condition</td></tr><tr><td>Avoidance of stimulants</td><td>Reduces palpitations, hyperarousal</td><td>Limit caffeine, nicotine, alcohol</td></tr><tr><td>Cognitive-Behavioral Therapy (CBT)</td><td>Improves mood and HRV in depression</td><td>Repetitive TMS sessions</td></tr><tr><td rowspan="2">Supportive</td><td>Transcranial Magnetic Stimulation (TMS)</td><td>Improves mood and HRV in depression</td><td>Repetitive TMS sessions</td></tr><tr><td>Deep Breathing & Baroreflex Training</td><td>Lowers high blood pressure, enhances calmness</td><td>6 breaths/min, daily sessions</td></tr><tr><td>Neuromodulation Therapies</td><td>Transcranial Magnetic Stimulation (TMS)</td><td>Improves mood and HRV in depression</td><td>Repetitive TMS sessions</td></tr></tbody></table>
<table><caption>**Table 4.** Pharmacological treatment modalities for autonomic dysfunction with their dosage regimens (typical adult doses).</caption><thead><tr><th>Medication type</th><th>Drug/therapy</th><th>Mechanism</th><th>Dosage ranges (Adults)</th></tr></thead><tbody><tr><td rowspan="2">Sympathomimetic Agents</td><td>Midodrine</td><td>α1-adrenergic agonist → vasoconstriction</td><td>2.5–10 mg orally 3 times/day (avoid within 4 hours of bedtime)</td></tr><tr><td>Droxidopa</td><td>Norepinephrine precursor → increases blood pressure</td><td>100–600 mg 3 times/day</td></tr><tr><td>Volume Expanders</td><td>Fludrocortisone</td><td>Mineralocorticoid → increases sodium & water retention</td><td>0.05–0.2 mg once daily</td></tr><tr><td rowspan="2">β-Blockers</td><td>Propranolol</td><td>β-adrenergic blockade → reduces tachycardia</td><td>10–20 mg 2–3 times/day</td></tr><tr><td>Bisoprolol</td><td>β1-selective blocker</td><td>2.5–5 mg once daily</td></tr><tr><td>Cholinesterase Inhibitors</td><td>Pyridostigmine</td><td>Inhibits ACh breakdown → enhances parasympathetic tone</td><td>30–60 mg 2–3 times/day</td></tr><tr><td>Central agent</td><td>Clonidine</td><td>α2-agonist → reduces sympathetic outflow</td><td>0.1 mg 2–3 times/day</td></tr><tr><td rowspan="3">Serotonergic Agents</td><td>Methyldopa</td><td>Central α2-agonist</td><td>125–250 mg 2–3 times/day</td></tr><tr><td>Fluoxetine</td><td>Enhances serotonin secretion → stabilizes blood pressure and heart rate</td><td>10–20 mg once daily</td></tr><tr><td>Citalopram</td><td>Enhances serotonin availability → stabilizes blood pressure and heart rate</td><td>10–30 mg per day</td></tr><tr><td>Norepinephrine Reuptake Inhibitors</td><td>Atomoxetine</td><td>Increases Norepinephrine availability</td><td>10–40 mg once daily</td></tr><tr><td>Adjunctive Therapies</td><td>Erythropoietin</td><td>Increases red cell mass → raises blood pressure</td><td>25–50 IU/kg 2–3 times/week (subcutaneous)</td></tr></tbody></table>

## 9. FUTURE DIRECTIONS

Autonomic dysfunction often presents complex and overlapping symptoms, which makes diagnosis difficult. Future research should focus on creating precise, non-invasive diagnostic tools (Figure 1). AI-assisted tests for autonomic functions, heart rate variability analysis, and wearable biosensors are some methods that could aid in early detection and real-time monitoring. Using remote diagnostics and digital health platforms can also provide ongoing assessment of autonomic indicators in everyday life. This approach could enhance diagnostic accuracy and customize treatment according to individual needs [60]. Finding reliable biomarkers is crucial for understanding the causes and progression of autonomic diseases. Future studies are expected to focus on genetic, protein, and metabolic profiling to identify molecular markers associated with different types of autonomic dysfunction. If we gain a better understanding of neuroinflammation, oxidative stress, and mitochondrial dysfunction, new treatment options may arise. Additionally, exploring the gut-brain axis could shed light on how changes in the microbiome influence autonomic function [61, 62].

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Future diagnostic tools for autonomic dysfunction.</figcaption></figure>
Conventional drug treatments often cure symptoms but do not address the root causes. Future therapies might focus on neuromodulation techniques, stem cell therapy, and neuroprotective substances. For example, transcranial magnetic stimulation, vagal nerve stimulation, and bioelectronic medicine could help restore autonomic balance. New advancements in gene editing technologies, such as CRISPR, may enable us to fix genetic defects associated with certain autonomic dysfunction. The strong connection between mental health and the autonomic nervous system highlights the need for treatments that work together. Future care models should include behavioral interventions, mindfulness exercises, and psychological therapy along with medical treatments. Research into the links between stress, mood disorders, and autonomic dysfunction could lead to better management techniques.

## 10. CONCLUSION

Autonomic dysfunction is a major sign of anxiety and depression. It connects emotional struggles with physical health problems. The imbalance between too much sympathetic activity and not enough parasympathetic activity leads to emotional issues, higher cardiovascular risk, and difficulty coping with stress. Therefore, it is crucial to monitor autonomic functions, as this may reduce the symptoms of these conditions. Treating autonomic dysfunction can lower the related health risks and deaths. There is a chance for better treatment of these disorders with methods that restore balance in the autonomic system. These methods can include medication, therapy, and natural remedies. By adding autonomic assessment to psychiatric evaluations, we can detect issues early, provide personalized treatment, and achieve better long-term outcomes.

**Competing interests:** The authors declare that they have no competing interest.

**Funding:** This research received no external funding.

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