The Presence of Serotonin in the Vestibular System: Supporting the Use of SSRIs/SNRIs in the Treatment of Vestibular Disorders—A Narrative Review

Objective: We reviewed the existing literature on Persistent Postural-Perceptual Dizziness (PPPD) and enquired about symptoms, diagnosis and treatments proposed in order to assess how concepts, diagnostic criteria and treatment have evolved over the last 10 years. Method: We conducted a systematic review of the literature. Results: PPPD is a frequent entity that has been only recently well described. Diagnosis relies on anamnesis; posturography is helpful. High scores of depression, neuroticism and introversion may be a risk factor for PPPD. 25% of cases may be triggered by neurotologic events such as Vestibular migraine, which is more prevalent than Meniere’s disease. There are alterations in activity and connectivity in the key central vestibular, visual and anxiety systems. Selective serotonin reuptake inhibitors (SSRI) and especially Sertraline could be the medication of choice. Other SSRI or Serotonin and noradrenaline reuptake inhibitors (SNRI) may be chosen in case of comorbid psychiatric disorders or insufficient response to the first choice medication. Cognitive behavioural therapy, vestibular and balance rehabilitation therapy seem to be effective. Conclusion: PPPD seems to stem from a multi-sensory maladjustment. Symptoms of Vestibular migraine, Meniere’s disease and PPPD are often overlapping, stressing the need for more precise diagnostic tools. Cognitive behavioural therapy and vestibular rehabilitation therapy have been recently proved to be effective therapeutic options for PPPD. However, there is little progress done concerning drug-treatments: SSRI and SNRI may help, but there is a need for larger controlled double-blind trials to confirm the effectiveness.

Perioperative vestibular assessment and testing

Persistent postural-perceptual dizziness (PPPD) (formerly chronic subjective dizziness) may be treated using the habituation form of vestibular and balance rehabilitation therapy (VBRT), but therapeutic outcomes have not been formally investigated. This pilot study gathered the first data on the efficacy of VBRT for individuals with well-characterized PPPD alone or PPPD plus neurotologic comorbidities (vestibular migraine or compensated vestibular deficits). Twenty-six participants were surveyed by telephone an average of 27.5 months after receiving education about PPPD and instructions for home-based VBRT programs. Participants were queried about exercise compliance, perceived benefits of therapy, degree of visual or motion sensitivity remaining, disability level, and other interventions. Twenty-two of 26 participants found physical therapy consultation helpful. Fourteen found VBRT exercises beneficial, including 8 of 12 who had PPPD alone and 6 of 14 who had PPPD with co-morbidities. Of the 14 participants who found VBRT helpful, 7 obtained relief of sensitivity to head/body motion, 5 relief of sensitivity to visual stimuli, and 4 complete remission. Comparable numbers for the 12 participants who found VBRT not helpful were 1 (head/body motion), 3 (visual stimuli), and 0 (remission). This pilot study offers the first data supporting the habituation form of VBRT for treatment of PPPD.

This article reviews the differences and similarities between persistent postural-perceptual dizziness (PPPD) and vestibular migraine. PPPD is considered a chronic functional vestibular disorder characterized by persistent dizziness, unsteadiness, nonspinning vertigo, and often exacerbated by upright posture, movement, or complex visual stimuli. Frequently misdiagnosed, PPPD shares overlapping features with vestibular migraine (VM), a common cause of episodic vertigo. A literature search was conducted covering articles published from January 2000 to March 2025 with a special focus on recent publications that discuss both PPPD and VM. Although some propose that PPPD is a chronic form of VM, its historical classification as a functional disorder, distinct from the neurological basis of migraine, may suggest otherwise. This review explores PPPD's diagnostic criteria, pathophysiology, and the differential diagnosis of VM, emphasizing the importance of identifying migraine symptoms to guide treatment. Evidence supports migraine prevention and specifically flunarizine as a primary preventive treatment for VM, with emerging data on calcitonin gene-related peptide-targeted treatments showing promise. For PPPD, however, vestibular rehabilitation therapy is a cornerstone treatment. A multidisciplinary approach addressing both conditions is critical for optimal patient outcomes. Studies on comorbid migraine treatment in patients with PPPD are warranted and may reveal distinct phenotypes within the same disease spectrum.

Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder, not a structural or psychiatric condition, presented by one or more dizziness, unsteadiness, or non-spinning vertigo symptoms. These symptoms will worsen with upright posture, movements, and exposure to complex visual stimuli. PPDD may be precipitated by disorders that impair balance or induce vestibular symptoms, such as peripheral or central vestibular diseases, other medical conditions, or psychological illness The exact pathophysiological mechanism is unknown, and it might result from functional adjustments to the postural control systems—alterations in the way multisensory information are processed or the integration of spatial orientation and danger perception in the cortex. PPPD is usually associated with co morbidities like anxiety. Subtypes of PPPD are phobic postural vertigo, space and motion discomfort, visual vertigo, and chronic subjective dizziness. PPPD is diagnosed according to the diagnostic criteria of the Barany society. Physical examination and diagnostic investigation are not pathognomic to PPPD. Treatment approaches include patient counseling, vestibular rehabilitation therapy, cognitive behavioral therapy, and medications.

Vestibular Migraine (VM) is a prevalent vestibular disorder, affecting up to 2.7% of the general population. Despite the establishment of diagnostic criteria by the Bárány Society and its inclusion in the International Classification of Headache Disorders, the clinical diagnosis of VM remains challenging due to its complex pathophysiology and symptom overlap with other dizziness disorders. Motion sickness is a core feature of migraine and can be interrogated through simple questionnaires. This study aims to identify to what extent motion sensitivity can predict VM compared to other causes of dizziness. We conducted a cross-sectional study involving 113 patients from the vestibular neurology clinics at University College London Hospitals. Participants were categorized into VM, Persistent Postural Perceptual Dizziness (PPPD), combined VM and PPPD, and 'other' dizziness etiologies. Data on motion sickness history and dizziness during car travel were collected through structured interviews and analyzed using logistic regression to assess the predictive value of these symptoms for VM. A substantial portion of patients with VM (91.2%) reported nausea or dizziness when reading as a passenger, a symptom significantly more prevalent than in those with PPPD or other dizziness diagnoses. Logistic regression indicated that VM patients are significantly more likely to experience these symptoms compared to non-VM patients, with an odds ratio suggesting a strong predictive value for this symptom in diagnosing VM. The findings highlight increased motion sensitivity while reading in a moving vehicle as a promising diagnostic tool for VM, offering a practical aid in clinical settings to distinguish VM from other vestibular disorders.

Persistent postural-perceptual dizziness (PPPD) is the most prevalent chronic functional dizziness in the clinic. Unsteadiness, dizziness, or non-spinning vertigo are the main symptoms of PPPD, and they are typically aggravated by upright posture, active or passive movement, and visual stimulation. The pathogenesis of PPPD remains incompletely understood, and it cannot be attributed to any specific anatomical defect within the vestibular system. Consequently, there is no objective examination method for the disease, and the diagnosis primarily depends on the symptoms of the patient, which lack specificity. To better understand the pathogenesis of PPPD and to aid in the development of novel diagnostic strategies and therapies, we conducted a comprehensive narrative review of the relevant literature. We performed a search for literature in PubMed using the following search phrases: "persistent postural-perceptual dizziness" OR "PPPD" OR "chronic subjective dizziness" OR "functional dizziness" OR "space-motion discomfort" OR "visual vertigo" OR "phobic postural vertigo." The reference list of relevant studies was also screened. The search was limited to publications in English, and the final references were selected based on their relevance to the scope of this review. This review summarizes recent studies that have investigated the pathogenesis of PPPD. It is traditionally assumed that PPPD may result from altered postural control strategies, cortical integration of threat assessment and spatial orientation, or abnormal integration of multi-sensory information. Recent studies have shown that the brain structure, activity, structural connectivity, and even cerebral perfusion of patients with PPPD differ from those of healthy individuals. Furthermore, PPPD patients are different from healthy individuals in spatial navigation ability, vestibular perception thresholds, central sensitization, and oxidative stress. These findings provide additional anatomical and behavioral insights into the pathogenesis of PPPD, suggesting that PPPD may arise from shifts in the interactions among emotional, visuo-vestibular, and sensorimotor networks. Understanding the complex pathogenesis of PPPD is crucial for the development of novel therapeutics against PPPD. Following the existing findings, our review suggests directions for future research.

BackgroundIndividuals with dizziness often face balance issues and anxiety, which can result in reduced physical activity levels and decreased participation in their daily activities. Few studies have evaluated physical activity levels in individuals with chronic dizziness, and none have specifically focused on the two most prevalent types: vestibular migraine (VM) and persistent postural perceptual dizziness (PPPD).ObjectiveEvaluate self-reported physical activity levels in individuals diagnosed with PPPD and VM who are awaiting vestibular rehabilitation.MethodsIn a retrospective cross-sectional study, we extracted data from the electronic healthcare records involving 121 individuals presenting either VM or PPPD, referred for vestibular rehabilitation at National Hospital for Neurology and Neurosurgery, University College London. Data on IPAQ (International Physical Activity Questionnaire) and DHI (dizziness handicap inventory) questionnaires were analysed across groups.ResultsThe total sample consisted of 94 (77.7%) women and 27 (22.3%) men with a median age of 56years old, ranging from 17 to 81years (P25 = 41 and P75 = 64). Regarding the total sample, a minority (9.1%) of the individuals scored a high activity level on the IPAQ. We observed a significant difference between VM and PPPD in IPAQ score distribution (p = 0.039, Mann-Whitney). Within the category of high physical activity, a larger proportion of individuals had VM compared to PPPD. An inverse correlation was found between DHI and IPAQ (the lower IPAQ, the higher DHI) in the PPPD group (p<0.003).ConclusionsIn a sample of individuals with PPPD and VM referred for vestibular rehabilitation, only a minority demonstrated high physical activity levels on the IPAQ, with PPPD exhibiting lower activity levels compared to those with VM.

Benign Paroxysmal Positional Vertigo (BPPV), Vestibular Migraine (VM), and Meniere Disease (MD) are among the most common episodic vestibulopathies. Persistent Postural Perceptual Dizziness (PPPD) is a chronic functional vestibular disorder that can arise in patients suffering from one or more of these conditions. We analyzed the role of these vestibular disorders as single or multiple associated comorbidities and as a precipitating condition for PPPD. A total of 376 patients suffering from dizziness with a known history of single or multiple vestibular disorders were preliminarily evaluated. We conducted a careful anamnesis to determine whether the reported dizziness could meet the diagnostic criteria for PPPD. PPPD was diagnosed in 24 cases; its incidence in patients with history of a single comorbidity or multiple vestibular comorbidities was 3.9% and 22.4%, respectively. BPPV, VM, and MD were identified as a precipitating condition in 2.34%, 16.45%, and 3.92%, respectively. BPPV constituted a precipitating condition mainly at the first episode. We observed that the presence of multiple vestibular comorbidities (BPPV, VM, and MD) in patients' clinical history increased the risk of PPPD. VM plays a significant role in representing a precipitating condition for PPPD, both when present individually or in association with the other vestibular disorders.

This paper presents diagnostic criteria for persistent postural-perceptual dizziness (PPPD) to be included in the International Classification of Vestibular Disorders (ICVD). The term PPPD is new, but the disorder is not. Its diagnostic criteria were derived by expert consensus from an exhaustive review of 30 years of research on phobic postural vertigo, space-motion discomfort, visual vertigo, and chronic subjective dizziness. PPPD manifests with one or more symptoms of dizziness, unsteadiness, or non-spinning vertigo that are present on most days for three months or more and are exacerbated by upright posture, active or passive movement, and exposure to moving or complex visual stimuli. PPPD may be precipitated by conditions that disrupt balance or cause vertigo, unsteadiness, or dizziness, including peripheral or central vestibular disorders, other medical illnesses, or psychological distress. PPPD may be present alone or co-exist with other conditions. Possible subtypes await future identification and validation. The pathophysiologic processes underlying PPPD are not fully known. Emerging research suggests that it may arise from functional changes in postural control mechanisms, multi-sensory information processing, or cortical integration of spatial orientation and threat assessment. Thus, PPPD is classified as a chronic functional vestibular disorder. It is not a structural or psychiatric condition.

To assess vestibular (i.e., passive self-motion) perception in patients diagnosed with persistent postural-perceptual dizziness (PPPD). Case-controlled, cross-sectional, observational investigation. Single-center laboratory-based study. Thirteen patients with PPPD, 13 age-matched healthy control volunteers. Of those with PPPD, eight had co-occurring vestibular migraine (VM). All participants completed a vestibular threshold test battery reflecting perception with predominant inputs from ( a ) the otoliths (1-Hz interaural y -axis translation, 1-Hz superior-inferior z -axis translation), ( b ) the semicircular canals (2-Hz yaw rotation, 2-Hz tilts in the planes of the vertical canal pairs), and ( c ) and canal-otolith integration (0.5-Hz roll tilt). Direction-recognition thresholds for each vestibular threshold test condition. Across all patients with PPPD, higher thresholds for superior-inferior z -translations thresholds in comparison to age-matched healthy control participants were identified ( p < 0.001). Those patients with co-occurring VM and PPPD (PPPD/+VM) displayed significantly higher z -translation thresholds ( p = 0.006), whereas patients with PPPD without VM (PPPD/-VM) displayed significantly higher roll tilt thresholds ( p = 0.029). Patients with PPPD did not display a global worsening of passive self-motion perception as quantified by vestibular perceptual thresholds. Instead, patients with PPPD displayed elevated thresholds for only roll tilt and z -translation thresholds, with the relative change in each threshold impacted by the co-occurrence of VM. Because both z -translation and roll tilt motions are reliant on accurate gravity perception, our data suggest that patients with PPPD may exhibit impaired processing of graviceptive cues.

Vestibular migraine (VM) is a usual trigger of episodic vertigo. Patients with VM often experience spinning, shaking, or unsteady sensations, which are usually also accompanied by photophobia, phonophobia, motor intolerance, and more. VM is often associated with a number of comorbidities. Recurrent episodes of VM can affect the patient's emotions, sleep, and cognitive functioning to varying degrees. Patients with VM may be accompanied by adverse moods such as anxiety, fear, and depression, which can gradually develop into anxiety disorders or depressive disorders. Sleep disorders are also a common concomitant symptom of VM, which significantly lower patients' quality of life. The influence of anxiety disorders and sleep disorders may reduce cognitive functions of VM, such as visuospatial ability, attention, and memory decline. Clinically, it is also common to see VM comorbid with other vestibular disorders, making the diagnosis more difficult. VM episodes are relieved but lingering, in which case VM may coexist with persistent postural-perceptual dizziness (PPPD). Anxiety may be an important bridge between recurrent VM and PPPD. The clinical manifestations of VM and Meniere's disease (MD) overlap considerably, and those who meet the diagnostic criteria for both can be said to have VM/MD comorbidity. VM can also present with positional vertigo, and some patients with VM present with typical benign paroxysmal positional vertigo (BPPV) nystagmus on positional testing. In this paper, we synthesize and analyze the pathomechanisms of VM comorbidity by reviewing the literature. The results show that it may be related to the extensive connectivity of the vestibular system with different brain regions and the close connection of the trigeminovascular system with the periphery of the vestibule. Therefore, it is necessary to pay attention to the diagnosis of comorbidities in VM, synthesize its pathogenesis, and give comprehensive treatment to patients.

PurposeTo evaluate the efficacy of vestibular rehabilitation therapy (VRT) for management of patients with persistent postural perceptual dizziness (PPPD) utilizing subjective and objectives outcome measures and to study the effect of degree of both anxiety and depression in patients on the response of vestibular rehabilitation therapy.MethodsThirty-three PPPD patients participated in this study. Selection of patients was based on the diagnostic criteria for PPPD stated by Barany society in the International Classification of Vestibular Disorders (2017). Every patient was subjected to history taking, anxiety and depression assessment, Arabic version of Dizziness Handicap Inventory (DHI), and sensory organization test (SOT). All patients received vestibular rehabilitations therapy. Assessment of VRT outcome was conducted after 6 weeks of VRT.ResultsThe mean patients’ age was 40.9 ± 16.3 years, and nearly equal gender distribution. Vestibular migraine was the most precipitating condition (24.2%) in patients with PPPD. (39.4%) of patients had abnormal scores of anxiety and depression tests, all patients had from moderate to severe degrees of handicap caused by dizziness as measured by DHI, most of patients had abnormal findings in all conditions of SOT. After vestibular rehabilitation therapy, DHI and SOT scores showed significant improvement after VRT. More improvement was found among the group with no anxiety and depression.ConclusionVRT were effective in improving balance abnormalities in patients with PPPD evidenced by subjectively by DHI scores and objectively by SOT results. PPPD patients with concomitant psychiatric disorders; anxiety and depression experienced the least degree of improvement.

In most cases, chronic dizziness is persistent postural perceptual dizziness (PPPD), which is often combined with other diseases of the vestibular system and anxiety disorders. In real-life clinical practice, PPPD and comorbid disorders are rarely diagnosed and effective treatments are rarely prescribed, so the development of modern methods for managing patients with PPPD with comorbid diseases is important.Objective: to analyze the typical management practices and evaluate the effectiveness of complex therapy in patients with PPPD and comorbid disorders.Material and methods. We examined 60 patients (mean age – 42.5±13.8 years) with diagnosis of PPPD (according to the diagnostic criteria of the Barany Society) and comorbid diseases. All patients were examined twice: at the beginning and after completion of treatment, which lasted an average of 1 month. Treatment included antidepressants (serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors), anti-anxiety medications, vestibular exercises, an educational program, and cognitive behavioral therapy. Arlevert (a combination of cinnarizine 20 mg + dimenhydrinate 40 mg) was used as a drug therapy for the treatment of vestibular dizziness in 28 patients. A clinical otoneurological evaluation and videonystagmography were performed to assess vestibular disorders; the severity of dizziness was assessed using an otoneurological questionnaire and the Dizziness Handicap Inventory (DHI); the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Spielberger Anxiety Inventory (STAI) were used to assess anxiety and depressive disorders.Results. None of the 60 patients had previously been diagnosed with PPPD. They were observed with a misdiagnosis of cerebrovascular disease and/or cervical spine pathology and received ineffective treatment. Anxiety and depressive disorders were detected in 32 (53.33%) patients, migraine – in 20 (33.33%) and previous peripheral vestibular disorders – in 8 (13.33%) patients. After one month of treatment in patients with PPPD and comorbid conditions, the severity of dizziness according to DHI decreased from 45.59±15.47 to 29.9±12.56 points (p&lt;0.001), the severity of anxiety according to BAI from 27.50±6.38 to 15.66±4.07 points (p&lt;0.001), the severity of depression according to BDI from 11.91±6.24 to 7.06±4.12 points (p&lt;0.001), the severity of anxiety according to HADS from 13.47±4.16 to 8.60±2.86 points (p&lt;0.001), the severity of depression according to HADS from 6.34±3.72 to 4.31±2.82 points (p&lt;0.001), situational anxiety according to STAI from 50.69±7.13 to 41.26±6.24 points (p&lt;0.001), personal anxiety according to STAI from 54.66±8.21 to 43.78±6.75 points (p&lt;0.001).Conclusion. It was found that PPPD is rarely diagnosed, and anxiety disorders, migraine and peripheral vestibular disorders are very common in PPPD patients. The integrated approach in the treatment of patients with PPPG, taking into account concomitant disorders, has demonstrated high efficacy.

Objective:To assess the status of anxiety and depression among patients with different type of vertigo and dizziness, and to figure out the possible reason. Methods:The data of the patients with vertigo from November 2017 to June 2020 were reviewed, and their status of anxiety and depression were assessed using self-rating anxiety scale（SAS） and self-rating depression scale（SDS）. Results:A total of 559 patients with vertigo were enrolled, including 94 cases for vestibular migraine （VM）, 86 cases for Meniere disease （MD）, 78 cases for benign paroxysmal positional vertigo （BPPV）, 77 cases for sudden hearing loss（SHL） with vertigo, 74 cases for no definite diagnosis, 58 cases for vestibular neuritis （VN）, 57 cases for benign recurrent vertigo （BRV） and 35 cases for persistent postural-perceptual dizziness （PPPD）.The incidence of anxiety is 43.11%（no definite diagnosis=64.86%, VM=63.83%, MD=55.81%, PPPD=48.57%, BRV=47.37%）, and the incidence of depression is 11.27% （no definite diagnosis=25.68%, PPPD=17.14%, VM=14.89%, BRV=14.04%, MD=12.79%）. Kruskal-Wallis test was used to analyze SAS and SDS scores of patients with vertigo. The results showed that there were significant differences in each group. All patients were divided into 3 groups according to the duration of vertigo. The anxiety incidence of >2 years group was highest（58.56%）, and the second one was 2 months to 2 years group（54.75%）. There was no statistically significant difference between 2 groups by χ²test（P>0.05）. But both of them were significantly higher than the <2 months group（17.30%）. The depression incidence of >2 years group was highest（32.43%）, the second one was 2 months to 2 years group（10.27%）, and the lowest one was <2 months group（0%）. χ² test（P<0.01） showed statistically significant differences among these three groups. Conclusion:Anxiety is more common among patients with vertigo than depression, and the patients who suffer from VM，MD，PPPD or BRV have significantly higher rates of psychiatric comorbidity.