What is Akathisia?
Akathisia is a neuropsychiatric condition characterized by intense restlessness and a strong desire to move. Patients with akathisia frequently report feelings of inner tension, anxiety, or discomfort that are only temporarily relieved by constant motion, such as pacing, shifting weight, or repetitive movements like tapping or rocking. This condition is frequently associated with the use of antipsychotic medications, particularly those classified as dopamine receptor antagonists (first-generation antipsychotics). It can also occur when taking certain antidepressants, antiemetics, or as a withdrawal symptom from certain medications.
Akathisia can appear suddenly (within hours or days of starting medication) or gradually (months or years after long-term drug use). Its symptoms can significantly reduce a patient’s quality of life, contributing to anxiety, depression, and even suicidal ideation if left untreated. Because akathisia can be misdiagnosed as worsening psychosis or anxiety, recognizing and correctly diagnosing it is critical for effective management.
Traditional and Standard Treatments for Akathisia
Historically, clinicians have struggled to treat akathisia due to its complex mechanisms and diverse presentations. The condition develops as a side effect of psychotropic medications, particularly antipsychotics. As a result, many traditional approaches to treating akathisia have centered on adjusting or discontinuing the offending drug, in addition to pharmacological interventions aimed at symptom relief. Let’s go over these standard treatments in greater detail.
1. Dose reduction or medication substitution
The first line of treatment for akathisia is often to reduce the dose of the underlying medication, especially if the akathisia is associated with the use of antipsychotics or antidepressants. Lowering the dosage can reduce the severity of symptoms, but this strategy is not always possible in patients who require high doses to manage severe psychiatric conditions like schizophrenia or bipolar disorder.
In some cases, switching to a different type of medication is necessary. Second-generation (atypical) antipsychotics, such as quetiapine and clozapine, are less likely to cause akathisia than first-generation (typical) antipsychotics like haloperidol or fluphenazine. A gradual transition from one medication to another under medical supervision is critical for avoiding a recurrence of psychotic symptoms while managing akathisia.
2. Beta-Blockers
Beta-blockers, particularly propranolol, are among the most commonly prescribed medications for the treatment of akathisia. Propranolol works by inhibiting the effects of adrenaline on the body, thereby alleviating physical symptoms such as restlessness, tremor, and anxiety. Its efficacy is thought to stem from its ability to influence both peripheral and central nervous system activity.
Several clinical trials have shown that propranolol can significantly reduce akathisia symptoms, particularly in the more severe forms. However, beta-blockers may not be appropriate for all patients, particularly those who have preexisting cardiovascular conditions such as bradycardia or hypotension, as the medication may exacerbate these issues.
3. Anticholinergic Agents.
Anticholinergic drugs, such as benztropine and diphenhydramine, are commonly used to treat extrapyramidal side effects caused by antipsychotic medications, and they have been shown to help with akathisia. These medications work by blocking acetylcholine receptors, which counteracts the dopamine blockade caused by antipsychotics.
However, anticholinergic drugs are not always effective in treating akathisia and can cause other side effects such as dry mouth, blurred vision, constipation, and confusion, particularly in elderly patients. As a result, they are frequently reserved for specific cases in which other treatments are ineffective or have failed.
4. Benzodiazepines
Another option for treating akathisia is to use benzodiazepines like lorazepam and clonazepam, especially if anxiety and agitation are prominent symptoms. These medications work by increasing the effects of gamma-aminobutyric acid (GABA), a neurotransmitter that promotes relaxation and lowers nervous system excitability.
While benzodiazepines can be effective in the short term, they also carry the risk of dependence and tolerance. Long-term use is generally discouraged due to the risk of abuse and withdrawal symptoms after discontinuation. As a result, benzodiazepines are typically prescribed for acute management rather than long-term treatment.
5. Serotonergic agents
Some evidence suggests that selective serotonin reuptake inhibitors (SSRIs), such as mirtazapine, may help reduce akathisia symptoms by regulating serotonin levels in the brain. Mirtazapine has proven particularly effective in cases where akathisia is linked to antidepressant use. Although serotonergic medications are not as commonly prescribed for akathisia as beta-blockers or anticholinergic agents, they are a second line of treatment, especially when other pharmacological options have failed.
6. Anticonvulsants
Gabapentin and pregabalin, which are commonly used for neuropathic pain and seizures, have shown promise in the treatment of akathisia. These drugs regulate calcium channels and reduce neuron excitability, potentially alleviating the restlessness associated with akathisia. Anticonvulsants are not first-line treatments, but they may be used in refractory cases or when other medications are contraindicated.
Limitations of Traditional Treatments
Despite the wide range of medications available, traditional treatments for akathisia have significant limitations. Not all patients respond to these therapies, and many of the medications used to treat symptoms have side effects of their own. Furthermore, the emphasis on symptom suppression rather than addressing the underlying cause of akathisia means that patients frequently receive insufficient relief, leading to frustration and continued distress.
As a result, there is a growing interest in developing new, more effective treatment modalities that address both the symptoms of akathisia and the underlying neurobiological mechanisms.
Groundbreaking Innovations in Akathisia Treatment
In recent years, advances in neuroscience, pharmacology, and digital therapeutics have sparked the development of novel approaches to akathisia treatment. These cutting-edge innovations provide hope to patients who have not responded to traditional treatments and may result in more comprehensive and long-term relief from this debilitating condition.
1. NMDA receptor modulators
One of the most promising areas of research for akathisia treatment is the use of NMDA receptor modulators. These drugs work by targeting the brain’s glutamate system, which regulates excitatory neurotransmission. Akathisia is thought to be caused by dysfunction in the dopaminergic and glutamatergic systems, and medications that modulate NMDA receptors may help restore balance and reduce restlessness.
Memantine, a medication commonly used to treat Alzheimer’s disease, is one example of an NMDA receptor modulator that has been shown to reduce akathisia symptoms. Early clinical studies indicate that memantine may be effective in cases of tardive akathisia (a type of akathisia that develops after long-term antipsychotic use), offering an alternative to traditional treatments that rely solely on dopamine regulation.
2. Cannabinoid-Based Therapy
Cannabinoid-based therapies have gained popularity in the treatment of a variety of neurological and psychiatric disorders, including akathisia. Cannabidiol (CBD), a non-psychoactive component of cannabis, is thought to have anxiolytic and neuroprotective properties, which could help with akathisia.
CBD interacts with the endocannabinoid system, which helps regulate mood, anxiety, and movement. CBD, by modulating this system, may help reduce the restlessness and agitation associated with akathisia while avoiding the psychoactive effects of tetrahydrocannabinol (THC), cannabis’ main psychoactive component. CBD’s therapeutic potential for akathisia is currently being investigated, but more large-scale studies are required to determine its efficacy and safety.
3. transcranial magnetic stimulation (TMS)
Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation technique that has shown promise for treating a variety of neuropsychiatric disorders, including akathisia. TMS uses magnetic fields to stimulate specific areas of the brain, particularly those involved in motor control and sensory processing.
TMS, which targets the prefrontal cortex and motor areas of the brain, may help reduce the abnormal motor activity and restlessness associated with akathisia. Early research has yielded promising results, with some patients experiencing significant symptom relief following a series of TMS sessions. TMS, with its non-invasive nature and lack of systemic side effects, is a promising alternative to pharmacotherapy, especially for patients who have not responded to traditional medications.
4. Gene Testing and Precision Medicine
The growing field of precision medicine opens up new avenues for personalizing akathisia treatment. Genetic testing, also known as pharmacogenomics, can identify individual variations in genes that influence drug metabolism, allowing clinicians to tailor treatment to each patient’s specific genetic profile. For example, some people may have genetic variations that make them more likely to develop akathisia while taking certain antipsychotic medications.
By identifying these genetic markers, healthcare providers can adjust medication regimens to reduce the risk of akathisia or select alternative treatments with fewer side effects. This personalized approach to treatment shows great promise for improving outcomes and reducing the trial-and-error process that often comes with medication management in akathisia.
5. Digital Therapeutics and Wearable Technology
The proliferation of digital therapeutics and wearable technology has created new opportunities for monitoring and managing akathisia. Wearable devices equipped with motion sensors, accelerometers, and biometric monitors can track patients’ movements and physiological responses in real time, providing useful information about the severity and frequency of akathisia symptoms. Clinicians can use this information to better understand restlessness patterns and tailor treatment plans accordingly.
Patients can use digital therapeutics, such as mobile apps and online platforms, to manage akathisia symptoms with tools like relaxation exercises, guided breathing, and mindfulness techniques. Some of these platforms also include cognitive-behavioral therapy (CBT) modules, which help patients deal with the anxiety and distress that are common with akathisia. These digital tools, which provide patients with real-time feedback and coping strategies, can supplement traditional treatments and empower patients to take a more active role in managing their condition.
Furthermore, the incorporation of machine learning and artificial intelligence (AI) into these technologies provides the potential for predictive analytics, allowing clinicians to anticipate exacerbations of akathisia and adjust treatment accordingly. This proactive approach to care may help prevent episodes of severe restlessness and improve overall treatment outcomes.
6. Novel antipsychotic medications
As research into the pharmacological causes of akathisia progresses, there has been a greater emphasis on developing newer antipsychotic medications with a lower risk of causing akathisia. These novel medications are intended to target dopamine receptors more selectively, reducing disruption to other neurotransmitter systems that contribute to the development of akathisia.
For example, third-generation antipsychotics like aripiprazole and brexpiprazole act as partial dopamine agonists, which means they modulate dopamine activity rather than completely blocking it, as traditional antipsychotics do. This mechanism reduces the risk of extrapyramidal side effects, such as akathisia, while maintaining the antipsychotic effects required to treat conditions such as schizophrenia and bipolar disorder. These medications provide a promising alternative for patients who are prone to developing akathisia while taking conventional antipsychotics.
7. Ketamine infusions
Ketamine, which was previously used as an anesthetic, has gained attention for its rapid-acting antidepressant properties and potential to modulate glutamate systems in the brain. Ketamine infusions have been studied as a treatment for refractory depression and anxiety, and new research suggests they may also be useful for managing medication-induced akathisia. Ketamine’s distinct mechanism of action, which involves NMDA receptor modulation, provides a new avenue for treating the severe restlessness and agitation associated with akathisia.
Although ketamine therapy for akathisia is still in its early stages of development, preliminary case reports suggest that it may provide relief for patients who have not responded to other treatments. Ketamine’s rapid onset makes it an appealing option for acute management of severe symptoms, especially in a clinical setting.
Challenges of Implementing Breakthrough Innovations
While these innovative treatments provide hope for patients with akathisia, widespread implementation faces several challenges. Access to cutting-edge therapies like TMS, ketamine infusions, and genetic testing may be restricted due to cost, availability, and insurance coverage. Furthermore, more research is needed to determine the long-term efficacy and safety of many of these treatments, especially cannabinoid-based therapies and digital therapeutics.
Despite these challenges, the ongoing development of novel treatments and technologies represents a significant advancement in the treatment of akathisia. As research advances and these therapies become more widely available, patients may benefit from more comprehensive and personalized treatment plans that address both the symptoms and underlying mechanisms of akathisia.
Alternative and Complementary Treatments for Akathisia
In addition to traditional and emerging medical treatments, many akathisia patients seek alternative and complementary therapies to alleviate their symptoms. These approaches emphasize holistic care, addressing the physical, mental, and emotional aspects of akathisia. While not a replacement for medical treatments, alternative therapies can help improve overall well-being and symptom management when used in conjunction with standard treatments.
1. Mindfulness & Meditation
Mindfulness practices, such as meditation and deep breathing exercises, can help alleviate the psychological distress associated with akathisia. Patients with akathisia frequently experience increased anxiety and agitation as a result of their physical restlessness, and mindfulness techniques can help them feel calmer and regulate their emotions.
Mindfulness meditation encourages people to focus on the present moment rather than dwelling on their discomfort or anticipating future symptoms. Mindfulness can help patients develop awareness and acceptance of their sensations, reducing the emotional reactivity that frequently exacerbates akathisia. Mindfulness-based interventions have been shown in studies to improve mental health outcomes for patients with anxiety and stress-related disorders, making them an effective complementary therapy for those suffering from akathisia.
2. Yoga and Physical Movement
Gentle physical activities such as yoga can help alleviate some of the physical discomfort associated with akathisia. Yoga combines controlled movement, breath work, and relaxation techniques to help patients relieve stress and increase body awareness. For people with akathisia, the controlled movement of yoga may help alleviate some of their motor restlessness, while the meditative aspects promote relaxation and stress reduction.
In addition to yoga, regular physical activity like walking or stretching can help relieve some of the physical symptoms of akathisia. Movement relieves the restlessness associated with the condition and can improve overall mood by increasing the production of endorphins, the body’s natural “feel-good” hormones.
3. Acupuncture
Acupuncture, a practice based on Traditional Chinese Medicine, has been studied as a complementary treatment for a variety of neurological and psychiatric disorders, including akathisia. The insertion of thin needles at specific points on the body is thought to balance the flow of energy, or “Qi,” while also stimulating the release of endorphins and other neurotransmitters that promote relaxation and reduce anxiety.
While the mechanisms underlying acupuncture’s effects are not fully understood in Western medicine, some studies indicate that it may be beneficial for conditions involving motor restlessness and agitation. Acupuncture could be used as an adjunct therapy for patients with akathisia, helping to alleviate some of the discomfort and emotional distress associated with the disorder.
4. Herbal and Nutritional Supplements
Several herbal supplements have been used to treat anxiety and agitation, and they may also be beneficial for people with akathisia. Common supplements that may help are:
- Valerian Root: Traditionally known for its calming properties, valerian root has been shown to reduce anxiety and promote relaxation.
- Passionflower: Passionflower, a herb known for its anxiolytic properties, may help relieve restlessness and agitation.
- Magnesium: This mineral aids nerve function and muscle relaxation, and magnesium supplementation may alleviate symptoms of restlessness and tension in some people.
Patients should consult with their healthcare providers before starting any herbal or nutritional supplements, as some may interact with prescription medications or worsen side effects.
5. Massage and Relaxation Techniques
Massage therapy has been used as a complementary treatment to relieve stress, promote relaxation, and increase circulation. Massage can help people with akathisia relieve the muscle pain and restlessness that comes with the condition. In addition to professional massage, self-massage techniques and massage tools such as foam rollers can help relieve muscle tension at home.
Incorporating relaxation techniques into daily routines, such as progressive muscle relaxation or guided imagery, can also assist patients with akathisia in managing their mental and physical symptoms. These techniques promote muscle relaxation and reduce the heightened arousal associated with anxiety, both of which can contribute to akathisia-related symptoms.
