Physiotherapy for patients with depression: Recent research progress

Abstract

Depression, a common mental illness, seriously affects the health of individuals and has deleterious effects on society. The prevention and treatment of depression has drawn the attention of many researchers and has become an important social issue. The treatment strategies for depression include drugs, psychotherapy, and physiotherapy. Drug therapy is ineffective in some patients and psychotherapy has treatment limitations. As a reliable adjuvant therapy, physiotherapy compensates for the shortcomings of drug and psychotherapy and effectively reduces the disease recurrence rate. Physiotherapy is more scientific and rigorous, its methods are diverse, and to a certain extent, provides more choices for the treatment of depression. Physiotherapy can relieve symptoms in many ways, such as by improving the levels of neurobiochemical molecules, inhibiting the inflammatory response, regulating the neuroendocrine system, and increasing neuroplasticity. Physiotherapy has biological effects similar to those of antidepressants and may produce a superimposed impact when combined with other treatments. This article summarizes the findings on the use of physiotherapy to treat patients with depression over the past five years. It also discusses several methods of physiotherapy for treating depression from the aspects of clinical effect, mechanism of action, and disadvantages, thereby serving as a reference for the in-depth development of physiotherapy research.

Key Words: Depression, Physiotherapy, Non-pharmacological, Rehabilitation therapy, Recent advances

Core Tip: Depression is a complex mental illness where a patient may exhibit a continuous, long-term low mood (a central feature). Psychotherapy and drug therapy are the most common treatments for depression; however, they have limitations. Physiotherapy is typically used to supplement or replace these therapies. In this study, the literature published in recent years was searched to identify the latest progress in physiotherapy for the treatment of depression and to provide empirical support for improving the cure rate and reducing the recurrence rate of the illness as much as possible.

INTRODUCTION

The incidence of depression has increased in recent years. Approximately 5% of adults worldwide suffer from depression[1], which has become a global health crisis and is the second largest health killer after cancer in humans. Depression gravely affects normal learning, work, and social activities. It has many manifestations and various pathophysiological mechanisms, including neuroplasticity and inflammation, which can result in diverse symptom patterns. However, no experts have clearly defined the causes of depression. People in different stages of depression exhibit different symptoms. The main signs are low mood, loss of interest and pleasure in things which were normally enjoyable, decreased attention, a low sense of self-worth and self-acquisition, a feeling of foreboding, suicidal ideation, and suicide[2]. Depression can increase the risk of cardiovascular disease, stroke, diabetes, and obesity, and can lead to suicide due to the inability to bear the pain of the illness. Depression is related to morphological and functional changes in different regions of the brain such as the frontal and parietal cortices, the hippocampus, and the thalamus or striatum[3]. These changes represent the basis for the cognitive and behavioral disorders observed in this pathology. For example, changes in the gray matter of the striatum are associated with suicidal tendencies, and dysfunction of the prefrontal cortex-amygdala-hippocampus circuit may be related to the visceral structure of the nerve, resulting in abnormal fear conditioning[4,5]. In traditional treatment methods, doctors often use psychotherapy and drug therapy to regulate the patient’s condition. Although this can improve symptoms of depression and anxiety, some patients experience a slow onset of the effects of medication. Long-term use of antidepressants is prone to causing adverse reactions (such as gastrointestinal discomfort), and users can easily relapse after drug withdrawal. This article reviews the literature on physiotherapy for depression over the past five years and discusses commonly used physical interventions to explore their value in the clinical treatment of patients with depression. We hope that this article will serve as a reference for improving the cure rate and reducing the recurrence rate of depression. Figure 1 shows the several types of physiotherapies introduced in this article.

Figure 1 Type of physiotherapy.

LITERATURE SOURCE

We collected and summarized the latest advancements in new technologies and parameters in the field of physiotherapy for depression. We used electronic and manual searches to retrieve articles on the physiotherapy of patients with depression in the PubMed database over the past five years (from 2018 to 2023). Electronic search terms included “depression”, “non-pharmacological therapy”, “electroconvulsive therapy”, “repetitive transcranial magnetic stimulation”, and “deep brain stimulation”. The literature that required manual searching was a list of references that emerged from the PubMed search process. We jointly negotiated to resolve or request third-party help when we disagreed about the literature retrieval and screening processes. Due to language limitations, we only included articles published in English.

ELECTROCONVULSIVE THERAPY

Electroconvulsive therapy (ECT) was first used more than 80 years ago and is an established medical practice[6]. It uses electrical means for physiotherapy; that is, through the qualitative discharge of the patient’s brain, the patient experiences a transient loss of consciousness to achieve the therapeutic effect. Generally, 8-12 instances of electricity are applied in one course of ECT at a frequency of 2-3 times per week. ECT can compensate for the shortcomings of traditional drug therapy to a certain extent such that many patients with a poor drug response also have the opportunity to recover.

The specific operational steps are as follows: First, two electrodes are placed on the bilateral temporal sides of the head, and then a certain amount of current is transmitted to the patient’s skull. After energization, the patient experiences brief convulsions and gradually loses consciousness. After these reactions occur, the patient’s head is shifted to one side, and the patient’s breathing is assisted until spontaneous breathing is restored[7]. Adults can usually tolerate a voltage of 70-130 V for 0.1-0.5 s or a current intensity of 90-120 mA for 1-3 s. Compared to other treatments, ECT is highly effective and is currently the main physical therapy used for depression. ECT is generally regarded as a last resort and is normally used after medication or psychotherapy has failed to produce a positive effect. ECT has excellent cost-effectiveness and should be included in a patient’s treatment plan as soon as possible[8]. However, ECT also has certain adverse reactions such as nausea, muscle pain, and headache; however, the duration is short, and the reaction is mild. If required, antiemetic drugs and simple painkillers can be used for symptomatic treatment. In the treatment of epilepsy induction and general anesthesia, ECT is a safe and well-tolerated treatment, and does not increase the risk of dementia or stroke[9]. Thus, the time required for patients to receive ECT can be extended appropriately. To prevent disease recurrence, the frequency of treatment should be gradually reduced when the patient improves, rather than immediately stopping treatment[10]. Table 1 outlines several studies that have used ECT to treat depression[11-15].

Table 1 Study of electroconvulsive therapy in the treatment of depression.

Ref.	Sample	Results
Abbott et al[11], 2021	Of 62 patients with major depressive disorder	The use of 800 mA and 600 mA is more effective in the treatment of depression, but patients with depression in the 800 mA group developed cognitive impairment after treatment
Su et al[12], 2023	Of 239 patients with depressive disorder	ECT is more effective in the treatment of patients with severe depression
Gryglewski et al[13], 2020	Of 13 patients with major depressive disorder	Twelve patients responded to ECT. The electrode placement position affected the change in the diffusion rate index
Cai et al[14], 2023	Of 183 adolescents with depression aged 13-18	After 6 wk of treatment, the ECT group experienced less suicidal ideation and fewer depressive symptoms
Su et al[15], 2019	Of 120 patients with major depressive disorder	The electrode-placed on the double frontal, double temporal, and right unilateral sides of the skull-was effective at treating depression

ECT: Electroconvulsive therapy.

REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION

Transcranial magnetic stimulation (TMS) is a non-invasive neuro-electrophysiological technique that interferes with brain function. A coil generates a high magnetic field, which induces a current in a specific area of the brain, depolarizes nerve cells, and changes the state of brain function. It was first discovered and developed by Barker et al[16] in 1985 and is used to treat depression[17]. Subsequently, other researchers modified the treatment technology based on problems encountered during the development process. They elaborated a treatment method called repetitive TMS (rTMS) that transmits TMS with repetitive pulses at short intervals[18]. In the past five years, researchers have used rTMS to treat many neurological and mental health conditions to study and evaluate its therapeutic effect[19-21]. rTMS does not require anesthesia, has low requirements for treatment sites (a person can even be treated in an office environment), it avoids the side effects and addiction that drug therapy may bring, and provides a safer treatment option for patients. Studies have shown that frontal lobe function in patients with depression is generally unbalanced. The use of low-frequency TMS (1 Hz, 5 times/week, 15 min/session, 20 times in total) of the right dorsolateral prefrontal cortex (DLPFC) can significantly reduce depression[22]. Between 30% and 50% of patients do not respond adequately to first-line treatment (a combination of drug therapy and psychotherapy). Traditional antidepressants target major neurotransmitters associated with depression such as serotonin, norepinephrine, and dopamine, and the treatment effect often differs markedly among individuals[23]. Although rTMS also has some side effects such as headaches and gastrointestinal discomfort, these may be related to the patient’s psychological pressure or physical condition; most side effects are limited in duration and do not lead to long-term adverse outcomes[24]. Despite its disadvantages, rTMS has significant benefits for patients with depression and can be used as an auxiliary physical therapy to treat the illness.

DEEP BRAIN STIMULATION

Deep brain stimulation (DBS) is an invasive technique. When the electrode is implanted into the brain, the patient is required to maintain consciousness. The pulse generators are used to stimulate certain nuclei in the deep part of the brain to correct abnormal brain electrical circuits, thereby reducing the patient’s neurological symptoms. The first trial of DBS in the treatment of depression by Mayberg et al[25] demonstrated its safety and efficacy. In general, when DBS is employed to treat depression, a fixed frequency (130 Hz) and pulse width (90 μs) are used, but two studies have tested the effects of different stimulation parameters[26,27]. In one study, the parameters were set as unipolar stimulation, the amplitude was 4 mA, and the pulse width was 91 μs; a low-frequency stimulation group (20 Hz) and a high-frequency stimulation group (120 Hz) were treated[26]. At 6 months, the treatment effect in the low-frequency group (20 Hz) was better than that in the high-frequency group (120 Hz), and at 12 months, high-frequency stimulation was better than low-frequency stimulation. The second study found no difference in the efficacy of DBS with a short pulse width (90 μs) and a long pulse width (210-450 μs)[27]. Transient adverse reactions after DBS such as ghosting, blurring, or dizziness, can be improved by reducing or changing the stimulation parameters. Available evidence suggests that DBS is an effective, safe, and well-tolerated treatment for depression. Open-label DBS studies of different targets have shown that if there is enough time to adjust the initial parameters, the average remission rate of patients with severe drug resistance can reach 50%[28]. DBS has the benefits of a strong recovery and minimal damage to the patient’s brain. It does not destroy the patient’s brain structure but only conducts the corresponding stimulation treatment on the brain[29]. The stimulation parameters of DBS can be adjusted according to the needs of patients, so it can provide a stable and lasting effect. The effect of drug therapy may be affected by various factors such as drug metabolism, individual differences, and disease progression, resulting in fluctuations in efficacy[30]. There are common problems with DBS treatment, including DBS hardware infection and DBS device battery depletion. No serious adverse events have been observed after proper treatment. Due to its many advantages, professionals have used DBS to treat depression and have achieved certain positive results in the early stages. However, the relevant theoretical research is still in the exploratory stage. Most experimental studies have conducted open-label trials. Problems exist such as a lack of control groups, small sample sizes, and difficulty excluding the placebo effect. With ongoing improvements in technology, it is possible to achieve outstanding value in the treatment of depression.

BRIGHT LIGHT THERAPY

Bright light therapy (BLT), as a physical intervention, is beneficial for treating various depressive disorders, including major and maternal depression; its mechanism may be related to the regulation of abnormal biological clocks, serotonin, and catecholamine systems[31]. Circadian rhythm disorder in patients with depressive disorder is often significantly altered by the sleep-wake cycle and hormone secretion. The effect of light timing on mood may be attained by regulating the phase shift and duration of the nocturnal melatonin secretion rhythm[32,33]. Melatonin induces the expression of Per1 and Per2 through the mediation of downstream protein kinase C to increase the resetting of the suprachiasmatic nucleus clock. Meyerhoff et al[34] found that BLT quickly improved symptoms of early insomnia, mental anxiety, drowsiness, and social withdrawal in patients with depressive episodes. Jiang et al[35] showed that high-intensity light could effectively improve the State Anxiety Scale scores of patients with subthreshold depression. Symptoms of anxiety are associated with a variety of neurotransmitters, including 5-hydroxytryptamine (5-HT), glutamic acid, norepinephrine, and gamma-aminobutyric acid. Light therapy can adjust the binding potential of 5-HT transporters in the anterior cingulate cortex, thereby regulating 5-HT levels. This is a mechanism by which BLT improves symptoms of anxiety. The focus of conventional drug therapy is to alleviate the patient’s depression, while the patient’s problems in other aspects are less of a concern. BLT can not only alleviate the symptoms of depression, but also improve the quality of sleep, adjust the sleep cycle, and help patients return to normal sleep patterns. It can also improve overall mental health, reduce anxiety and depression, and help patients to fully recover their health[36,37]. The ideal time to receive intense light therapy is mostly within 10 min after waking, but the treatment cycle is not yet clear; the most common side effects after treatment are headaches and eye problems[38]. Although the effectiveness of phototherapy in the treatment of depression is relatively accurate, the specific optimal configuration of factors - such as light dose (light irradiance, irradiation time, light source distance, and angle), spectrum, and daily exposure time, which affect the clinical efficacy and side effects of phototherapy - has not yet been determined. Further research is required to explore its clinical applications. Table 2 lists several studies that have used BLT therapy[39-42].

Table 2 Related research on bright light therapy.

Ref.	Sample	Results
Donmez et al[39], 2022	Of 30 cases of pregnant women and postpartum 1-yr patients with depression	BLT effectively alleviated patients’ depression
Raymackers et al[40], 2019	Of 59 breast cancer patients with depressive symptoms	The efficacy of BLT is better in spring and summer
Rutten et al[41], 2019	Of 83 patients with depression and Parkinson’s disease	BLT had little impact on the alleviation of patients’ depression but effectively improved their sleep status
Chan et al[42], 2022	Of 93 patients with non-seasonal depression	The remission rate of BLT therapy in the treatment of non-seasonal depression was relatively high

BLT: Bright light therapy.

TRANSCRANIAL DIRECT CURRENT STIMULATION

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that transfers a weak direct current to the surface of the cerebral cortex through at least two electrodes, causing changes in the resting membrane potential hyperpolarization or depolarization to regulate cortical excitability and neural network activity[43]. In patients with depression, left DLPFC activity is weakened, blood flow is reduced, metabolism is slowed, and right DLPFC activity is overly enhanced, resulting in an imbalance in DLPFC function on both sides. Hence, the anode of tDCS can be used to stimulate the left DLPFC to improve its excitability, while the cathode can be used to stimulate the right DLPFC to inhibit its excitability, thereby regulating the activity of the brain’s emotional loop and alleviating depression[44]. Common adverse reactions such as itching, burning, and headaches are usually mild and do not cause long-term effects[45]. Compared with other neuromodulation methods, tDCS is cost-effective, portable, safe, easy to use, and has considerable therapeutic potential.

VAGUS NERVE STIMULATION

Although vagus nerve stimulation (VNS) was initially widely used to treat epilepsy (and not depression), because it can effectively improve the mood of patients with epilepsy, VNS has been extended to include mental disorders such as depression. In 2005, the Food and Drug Administration in the United States officially approved VNS for the treatment of depression[46]. It has been rapidly developed and has achieved positive outcomes. Through surgical implantation of a VNS device, a bipolar stimulation electrode is configured as the cathode of the proximal lead and the anode of the distal lead. A pain block is established in the distal lead and the action potential is guided to the central nervous system (CNS). Sending electrical pulses to the left cervical vagus nerve stimulates the brainstem pathway of the afferent vagus nerve related to emotional regulation, thereby treating depression[47]. Bottomley et al[48] showed that VNS can prolong the duration of antidepressant efficacy and alleviate depressive symptoms in patients. Safety issues related to VNS are minimal. However, the treatment cost of VNS is relatively high, which may pose a certain burden on some patients with limited economic resources. This problem requires consideration.

ACUPUNCTURE

Acupuncture is a promising non-drug treatment for reducing depressive symptoms and can replace drug therapy or complement other therapies to improve outcomes. Manual acupuncture is a traditional technique; a fine metal needle is used to pierce the skin at an acupoint and is then operated by hand through lifting, pricking, and twisting. Compared with drug treatment, acupuncture is affordable and has few side effects[49,50]. From the perspective of traditional Chinese medicine (TCM), the incidence of depression is related to patients’ mood and visceral dysfunction. Stimulating specific acupoints of the human body, enhancing the input signal of the motor cortex, and increasing the excitement of the CNS may improve the patient’s depressive state and regulate the expression of regulatory T cells, thereby mitigating the immunosuppressive state of depression[51]. Acupuncture treatment usually does not produce drug dependence and resistance, nor does it cause damage to liver and kidney function. Although acupuncture has a certain effect in the treatment of depression, its onset time may vary from person to person. For some patients, multiple treatments may be required to see a significant improvement. Due to the need to stimulate acupuncture points in acupuncture treatment, some patients may be unable to accept this treatment because of fear or discomfort with needles[52].

CHIROPRACTIC MANIPULATIVE TREATMENT

Chiropractic manipulative treatment (CMT) is a massage technique used in TCM; it is combined with the rolling method, lifting, pinching, and point pressing to stimulate the governor vessel and bladder meridians to relax the tendons and dredge the collaterals, thus regulating qi and blood. The symptoms of depression, such as high cortisol, high adrenaline, insomnia, restlessness, and anxiety can be attributed to excessive activity of the sympathetic nervous system[53]. Additionally, dopamine, brain-derived neurotrophic factor, nerve growth factor, and other neuroendocrine factors play a role in the pathophysiology of depression. As a potential treatment, CMT uses spinal finger pressure therapy and VNS to activate the parasympathetic nervous system, reduce the activity of the sympathetic nervous system, synthesize neuroendocrine factors to regulate the autonomic nervous system, and mitigate the symptoms of autonomic nervous imbalance and depression[54].

DISCUSSION

Depression is a common psychiatric disorder characterized by symptoms such as low emotion, a slow thinking response, laziness, and slow movement. It can be accompanied by different degrees of cognitive impairment, which has many negative effects on daily life, work, studying, and social interactions. In severe cases, dangerous behavioral tendencies may occur such as violence and suicide. With the continuous development of bioengineering technology, additional physical therapy approaches are expected to be developed. Thus, professionals in relevant fields must implement reforms and innovations based on existing physical therapies. This article lists several commonly used physical therapies and rehabilitation methods for depression, including ECT, rTMS, and DBS to provide a reference for clinical medical staff when selecting appropriate interventions. Among them, ECT and rTMS have been used for a long time, with more evidence demonstrating a curative effect[55-58]. New physical therapies such as DBS, VNS, and CMT have fewer clinical trials, lack evidence, and need to be further studied[29,53,59].

Currently, ECT is the most efficient form of physical therapy. It can be used to treat patients as soon as possible following an injury or illness. It is extremely safe, has few side effects, and does not lead to dependence on drug treatment[8,9]. Kirov et al[6] and Gyger et al[7] confirmed the effectiveness and safety of ECT[6,7]. Even so, professionals working with various media and many studies have been skeptical of ECT. Other neuromodulation techniques such as rTMS, DBS, and tDCS have been approved and used; however, there is insufficient evidence to confirm their efficacy. It is gratifying that in the past five years of research, people’s attention to physical therapy has gradually increased. Researchers have verified the effectiveness and safety of the above treatment techniques from different perspectives and have explored ways to achieve better efficacy[21,26,27,46]. Most of the time, satisfactory results can be obtained. Occasionally, the outcomes are poor due to various limitations; however, this is a normal phenomenon in research. There are also milder therapies such as BLT. These techniques do not require a high-quality treatment environment and are simple to perform. However, their therapeutic effects are inferior to those of other neuromodulatory approaches. The milder therapies can be used to treat patients with mild depression or as an adjuvant therapy. TCM is widely employed in China. In the treatment of depression using physical methods, the most used approaches are acupuncture and CMT[50,51,54], which are also relatively mild treatments.

CONCLUSION

The current visiting rate of diagnosis of depression is low in China, and the incidence of depression is increasing in the young, which has extremely serious repercussions at the economic and societal levels. There are many types of physical therapies, and the curative effect may differ owing to different stimulation positions, stimulation currents, and time settings. Compared with the conventional treatment of depression, the use of physical therapy for depression does not require surgery, injections, or the use of drugs, therefore the risk of side effects or dependency is very low. Additionally, the adverse effects are usually mild and can be solved by proper treatment. However, some of the milder physical therapy methods have no obvious effect in the short term. This requires the long-term persistence of patients to achieve results, and sometimes needs to be combined with other treatment methods. Based on the existing stage, combined with the advantages of technological development, more scientific clinical research is being conducted to create additional physical therapy methods in line with reality and to reduce the prevalence of depression. Moreover, because the combination of physical therapy with drug therapy and psychotherapy may enhance the antidepressant effect, in addition to designing relevant clinical trials to determine whether a new physical therapy has an antidepressant effect, it is necessary to explore the effectiveness of physical therapy combined with antidepressant drugs as well as that of psychotherapy combined with antidepressants. This should be done to enable the selection of different treatment techniques according to different symptoms to obtain a more obvious curative effect. The occurrence of depression is not caused by a single factor but rather by the comprehensive application of a complex social environment. Hence, attention must be paid to prevention, treatment, popularizing science, choosing from a myriad of treatment methods, improving the clinical cure rate of depression, minimizing the occurrence of suicide, reducing the recurrence rate, and increasing the survival and well-being of patients.