Persistent Postural-Perceptual Dizziness (PPPD) is a chronic functional vestibular disorder that is characterized by identifiable and unique sets of symptoms, comprising three main symptom clusters: dizziness, unsteadiness, and non-spinning vertigo that is present on most days for 3 or more months,1,2 which may be exacerbated by upright posture, active or passive motion stimuli without regard to direction or position, and exposure to moving visual stimuli or complex visual patterns, and may be precipitated by conditions that cause vertigo, unsteadiness, dizziness, or problems with balance.3,4 In tertiary dizziness centers, PPPD is the second most common diagnosis, accounting for approximately 15%–20% of cases.5 PPPD is often underestimated in community patients because related symptoms are easily overlooked, resulting in many patients not receiving early and accurate diagnosis and treatment.

Although PPPD is a new medical term, the phenomenon has long been recognized as a disorder of spatial orientation and motor sensory abnormalities. In the past 30 years, from the initial presentation of Phobic Positional Vertigo (PPV) to the subsequent presentation of Spatial Motion Discomfort (SMD), Visual Vertigo (VV), and Chronic Subjective Dizziness (CSD), the 2017 Bárány Association summarized and summarized the common issues related to PPV, SMD, VV, and CSD, whose commonalities form the basis of the diagnostic criteria for PPPD.1,3 However, after searching in related fields, no Randomized Controlled Trials (RCTs) of PPV, SMD, or VV were found. As a result, six RCTs including patients with PPPD and CSD were included in the meta-analysis.

Although some debate remains, the most widely accepted putative mechanism of the pathogenesis of PPPD comprises a developmental process that involves functional, psychological, and structural disorders. The model of the mismatch between function and vestibular needs has been gradually accepted as explaining the probable mechanisms of PPPD. For a person without PPPD experiencing a precipitant vestibular crisis, medical event or acute psychological distress, acute adaptation including visual-somatosensory dependence, high-risk postural control strategies, and environmental vigilance may lead to neurotologic, medical, and behavioral recovery. After postural threats subside, the aforementioned strategies are typically abandoned. For patients with PPPD, however, additional predisposing factors such as neurotic temperament and pre-existing anxiety may cause behavioral comorbidity, including anxiety, and depressive and somatic symptom disorders. These factors can induce a vicious circle of maladaptation that is driven by perpetuating factors, including visual dependence, stiffened postural control, and decreased cortical integration, and provoking factors including upright posture, motion of self, and visual demands. Importantly, acute anxiety and body vigilance of PPPD patients can exacerbate the vicious circle mentioned above. Moreover, previous studies have indicated that damage of specific brain areas that are responsible for high-level spatial orientation, multi-sensory integration, and threat assessment plays a role in the mismatch of incoming and outgoing signals.6,7

On the basis of current understanding of PPPD, a number of symptomatic treatments are recommended in patients with PPPD.2 These treatments are designed to reduce the patient’s anxiety traits to decrease the seizure of disease, or to improve the patient’s vestibular function to alleviate the symptoms of dizziness, unsteadiness, or vertigo. Vestibular Rehabilitation Therapy (VRT), which is generally used to treat vestibular diseases, aims to rebuild the balance system, focusing on high-risk postural control strategies, visual-somatosensory dependence, and environment vigilance.8–10 Additionally, Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) and selective Serotonin Reuptake iInhibitors (SSRIs) are commonly used in PPPD, mainly ealleviate mood disorders.11

Cognitive Behavioral Therapy (CBT) is a psychosocial intervention that has become the most widely used practice for improving mental health and is commonly used in patients with mild to moderate anxiety and depression.3 CBT is a counseling and treatment method that focuses on patients’ irrational cognitions and behaviors to improve negative emotions, and is a recommended treatment for PPPD.12,13 CBT can provide talk therapy and stress management strategies to help patients understand and cope with their symptoms, focusing on the fear of falling, health anxiety, and avoidance behavior. CBT may benefit PPPD patients by reducing excessive physical alertness and fear of dizziness or falling down, and confronting anticipatory anxiety, and supplemental physical therapy can be performed to help patients become accustomed to exposure to reduce corresponding acute anxiety and body vigilance.8,10 Because of its advantages, including a lack of side effects, low risk of potential harm, and convenience of administration, CBT has come to play an increasingly important role, and has received an increasing amount of attention from clinical physicians.

However, very few RCTs have studied the clinical efficacy of CBT in PPPD to date, and have typically had a small sample size, substantial variation in quality, and a lack of evidence-based evidence. Thus, a structured CBT intervention protocol that can strongly prove its efficiency and guide clinical practice has not yet been developed. To the best of our knowledge, no previous meta-analysis has statistically quantified the efficacy of CBT in PPPD. Therefore, the current meta-analysis aimed to collect and analyze available RCT data to provide a high-level evidence base regarding the efficacy of CBT and inform its application in the clinical field.

The current meta-analysis aimed to investigate the efficiency of additional CBT for patients with PPPD compared with conventional therapy alone. Because of the continuous optimization of the concept of PPPD, PPPD and its four subtypes (CSD, PPV, SMD, VV) were all intended to be incorporated in the meta-analysis. However, the literature search revealed no RCTs examining PPV, SMD, or VV. As a result, six RCTs examining patients with PPPD and CSD were included in the meta-analysis.

The selection of outcome indicators was based on the main symptom clusters and corresponding anxiety or depression. The six RCTs focused on different areas using different outcome indicators, resulting in only a few common indicators that could be examined in the meta-analysis. Finally, the DHI, which focuses on vestibular symptoms including dizziness, unsteadiness, and vertigo, as well as physical ability, functional balance, and emotional status, and the HAMA, GAD-7, and PHQ-9, which are focused on corresponding anxiety, were selected for use in the meta-analysis. Among these, the DHI, GAD-7, and PHQ-9 were self-rating scales, and HAMA was an examiner-rating scale.

After searching studies according to the search strategy, the relevant information, and data of the included RCTs were extracted for analysis, and ROB 1.0 was used to evaluate their corresponding risks to assess quality. The I2 test showed low heterogeneity among all studies which suggested that the corresponding results were credible. As a result, a fixed-effects model was used.

DHI and anxiety- or depression-related scales were used to evaluate the efficacy of CBT in the meta-analysis. DHI is the most widely used scale for assessing the self-perceived handicapping effects of vestibular system disease, via self-assessment of disability associated with dizziness.21 Regarding the main outcome (DHI-Total scores), our meta-analysis of six studies suggested that additional CBT has significant benefits compared with conventional therapy alone. Additionally, the subgroup analysis showed significant benefits of additional CBT compared with VRT alone, SSRI alone, and VRT combined with SSRI. Moreover, regarding the main outcome of DHI-Functional, Physical and Emotional scores, four studies indicated that additional CBT has significant benefits compared with conventional therapy alone, and subgroup analysis showed significant benefits of additional CBT compared with VRT alone, SSRI alone, and VRT combined with SSRI. It should be noted that, in the subgroup analysis, although CBT was shown to be significantly effective compared with conventional therapies when used in combination, presenting CBT alone without combination with conventional therapy unexpectedly induced no additional significant improvement compared with a blank control group. However, caution should be exercised when drawing conclusions about whether CBT alone provides benefit in PPPD, because only one RCT included a CBT-only subgroup.16 This study was evaluated as having a high risk of bias, and the baseline was not balanced, with baseline DHI-Total scores in the control and experimental groups of 53.80 and 42.10, respectively, and outcome DHI-Total scores in the control and experimental groups of 26.80 and 34.76, respectively.16 Thus, more RCTs are warranted to explore whether CBT alone is effective without being used in combination with conventional therapy.

HAMA is the most widely-used examiner-rating scale, and is designed to measure the severity of anxiety neurosis,22 which may provide a measure of the change of anxiety before and after treatment, indicating that additional CBT provided effective relief for somatic anxiety and psychic anxiety in PPPD patients.23 The GAD-7 and PHQ-9 are commonly used self-rating scales for assessing patients’ anxiety, and have been shown to demonstrate excellent internal consistency.24–26 Regarding the secondary outcomes of HAMA, GAD-7, and PHQ-9 scores on the basis of our meta-analysis, additional CBT was associated with significant benefits compared with conventional therapy alone. However, it should be noted that only two studies for each of the HAMA, GAD-7, and PHQ-9 were included in the analysis.

Sensitivity and bias analysis were conducted. A sensitivity analysis in which each of the six studies was excluded and a random-effects model was used revealed no differences, indicating that the results of the meta-analysis were stable. The funnel plots indicated that the publication bias of the reviewed studies was mild and unlikely to affect the results, but also indicated that the number and sample size of studies were small, and few studies with negative results were identified.

The results indicated that additional CBT combined with conventional therapy could be beneficial for patients of PPPD in terms of physical ability, which reflects the severity of vertigo itself, functional balance, which reflects the degree of impact of vertigo on the patient’s mood, and emotional status, which reflects the degree of hindrance of vertigo to life, work, and social interaction, by reducing the patient’s anxiety level, which is an important factor in the vicious circle of maladaptation of PPPD.

The use of CBT in treating PPPD is primarily based on a theoretical framework in which anxiety is the core content of the psychophysiological model of the disease.5,27,28 Dizziness symptoms activate the human body’s internal threat response system, which increases the patient’s perception of motion stimuli. This can lead to PPPD and anxiety. When anxiety is induced, physical symptoms such as dizziness then occur, and mental and psychological mechanisms maintain these symptoms.1,5 CBT focuses on the fear of falling, health anxiety, and avoidance behavior through talk therapy or stress management strategies, and can help patients understand and cope with their symptoms. Additionally, CBT may offer patients with PPPD benefits by reducing excessive physical alertness and the fear of dizziness or falling down, and confronting anticipatory anxiety, as well as supplemental physical therapy to help patients become accustomed to exposure to reduce corresponding acute anxiety and body vigilance.8,10 CBT may be useful for correcting irrational cognition of patients with PPPD to enable cognitive reconstruction, and combining CBT and relaxation training may reduce or eliminate anxiety, fear and other negative emotions and corresponding physiological reactions, as well as promoting the improvement of symptoms and functional recovery, thereby producing therapeutic effects. Previous studies have reported that, when undergoing VRT, some patients feel very uncomfortable when exposed to eliciting stimuli, and exhibit aggravated anxiety reactions after treatment; techniques such as explanation, support, and behavioral relaxation using CBT may be useful in such situations.3,5,27 Thus, CBT may play a helpful role in providing timely and effective interventions to reduce emotional and psychological reactions in patients, enhance confidence, ensure smooth progress of rehabilitation, and improve curative effects.5

Overall, the current meta-analysis of multi-faceted questionnaire findings indicated that CBT significantly improved vestibular symptoms, mood, and social function. On the basis of an integrated analysis of RCT evidence, high-level recommendations can be made. The current findings suggest that it may be helpful for doctors to assess the subjective symptoms of patients with vertigo as a whole by counting the negative impact of vertigo on the patient’s body, emotional state, function and its severity. This approach may be conducive to the classification and screening of patients to determine individualized treatment plans, and evidence-based suggestions for improving the quality of life of patients with vertigo. However, more RCTs with larger sample sizes are still needed to further support the effectiveness of CBT for patients with PPPD.

The results of the current meta-analysis suggest that additional CBT combined with conventional therapy may provide significant benefits compared with conventional therapy alone for patients with PPPD. The meta-analysis revealed significant improvements in outcomes assessed using the DHI, HAMA, PHQ-9, and GAD-7. However, the limited number of RCTs prevented more definitive conclusions from being drawn, which indicates that more data are still needed to support and guide the application of CBT in the treatment of PPPD. With the rapidly growing international interest in advances in this field, there is substantial potential for CBT in the treatment of PPPD.

This meta-analysis was supported by Natural Science Foundation of Beijing (Grant nº 7222237), on the mechanism of the central static compensation-related cerebellum-medial vestibular nucleus nerve pathway in Unilateral Peripheral Vestibular Disease (UPVD).

The authors declare no conflicts of interest.