Bipolar Affective Disorder is a debilitating disease that can potentially result in severe impacts on a individual’s personal and professional life. It is one of the leading causes of disability around the world. Bipolar patients are more likely to have their marriages end in divorce, be terminated from their job, suffer from financial ruin, strain relationships, and attempt suicide. Unfortunately, bipolar disorder is often misdiagnosed, which can leave patients untreated for years or lead to inappropriate treatments, thereby delaying the proper interventions needed to manage the condition effectively. Bipolar disorder also has a high rate of recurrence even when treated with conventional pharmacotherapies and psychotherapies. This is especially true with bipolar depression.
AVYIA’s ketamine program treats the depressive symptoms of bipolar rapidly, often providing noticeable symptom relief within the first treatment session. Ketamine is also safe, has minimal side effects, and is generally well-tolerated. Patients that suffer from bipolar should always have an established health care provider manage their disease because of the seriousness and complexity of the disorder. Oftentimes, patient’s are on multiple medications to manage their symptoms. AVYIA’s ketamine therapies are an adjunctive treatment to combat the depressive symptoms associated with bipolar disorder. In other words, ketamine works together with a patient’s existing regime of mood stabilizing medications, anti-psychotics, and psychotherapies. As such, AVYIA advises patients with bipolar disorders to continue following their existing mental health provider’s treatment regime while receiving ketamine therapy.
National Institute of Mental Health (NIMH) estimates 4.4% of adults in the United States experience bipolar disorder at some point in their lives. This translates to approximately 11.2 million people in the US.
The average age of onset for bipolar disorder is 25 years old, although it can occur in childhood or later in life. About 1% of children and adolescents experience bipolar disorder.
Bipolar disorder affects both men and women equally. However, women may be more likely to experience rapid cycling (four or more mood episodes in a year) and have more depressive episodes than men.
Bipolar disorder often co-occurs with other mental health conditions, such as anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), eating disorders, and personality disorders.
Bipolar disorder can cause significant disability, impacting an individual's ability to work, attend school, and maintain relationships. In fact, bipolar disorder is the sixth leading cause of disability worldwide among people aged 15-44.
While effective treatments for bipolar disorder exist, many individuals with the condition do not receive proper care. Only about half of people with bipolar disorder receive treatment for the condition. Access to care can be further limited by factors such as stigma, cost, and a shortage of mental health providers.
Bipolar disorder, formerly known as manic depression, is a prevalent and incapacitating mental health condition affecting millions of individuals worldwide. This complex disorder is characterized by intense fluctuating shifts in mood, or mood swings, that can severely impact a person’s daily life and overall well-being. Depending on the symptoms and severity of these mood swings, these episodes are either called manic or hypomanic (also referred to as mania and hypomania).
One of the complexities of bipolar disorder is its variability in symptom presentation and the frequency of mood swings. Some individuals may experience episodes rarely, with long periods of stability in between, while others may have more frequent mood swings, with episodes occurring multiple times a year. Despite the challenges associated with bipolar disorder, with the correct support, therapy, and adherence to treatment, many individuals can achieve stability and lead fulfilling lives.
There is a genetic correlation associated with bipolar disorder. Individuals with family members that have bipolar disorder are more likely to develop bipolar themselves compared to the general population. Bipolar disorder is typically triggered by significant life events or stressors, such as having a marriage end in divorce, losing a loved one, being fired from a job, or suffering from financial ruin. Furthermore, brain chemistry and brain structure play a crucial role in mood regulation. Imbalances in neurotransmitters, such as serotonin, dopamine, and norepinephrine, have been associated with bipolar disorder. Certain drugs that can affect brain chemistry may trigger or worsen bipolar symptoms in some individuals. In fact, there are some studies that suggest SSRI antidepressants can trigger the onset of bipolar disorder. Therefore, care under a mental health care provider is of the upmost importance for anyone experiencing mental health symptoms.
While the factors discussed above are associated with the development of bipolar disorder, they do not guarantee that an individual will develop the condition. On the other hand, the absence of those risk factors do not rule out the possibility of developing bipolar disorder. More importantly, being familiar with the symptoms and getting a qualified mental health professional to diagnose the disorder is the first step towards effective treatment.
The rates of response and remission after the seventh infusion of ketamine were 61.5% and 46.2%, respectively. A significant antisuicidal effect was observed in responders at the 7th infusion. Suicidality was measured with item 10 on the MADRS scale. The average time to respond was between 21.1 and 23.2 days to remission…No serious adverse events, however, were observed…This report presents the preliminary results of IV ketamine effectiveness and safety in treatment-resistant bipolar depression. The findings suggest that it is a feasible, safe and well-tolerated treatment option in this group of patients.
Wilkowska, A., Włodarczyk, A., Gałuszko-Węgielnik, M., Wiglusz, M. S., & Cubała, W. J. (2021). Intravenous ketamine infusions in treatment-resistant bipolar depression: An open-label naturalistic observational study. Neuropsychiatric Disease and Treatment, 17, 2637–2646. https://doi.org/10.2147/ndt.s325000
Bipolar I episodes are characterized by manic episodes lasting anywhere from seven days or more. It's then followed by depressive episodes that can last anywhere from two weeks or more. These episodes are severe enough to require hospitalization. Manic episodes can possibly lead to exhaustion and self harm.
Bipolar II is characterized by cycles of hypomanic and depressive episodes, although less severe than those of Bipolar I.
It is characterized by highs and lows that don't meet the criteria for depression or hypomania. Depressive symptoms last for at least two years. Mania, hypomania, and depressive episodes can still be dangerous.
Due to its unique way of action, ketamine seems to be crucial for the treatment of anhedonia…Literature suggests that intravenous ketamine 0.5 mg/kg over 40 min weekly could be useful in the treatment of bipolar depression with prominent anhedonia, but there is still a small number of studies that examine the efficacy of ketamine infusions in BD [bipolar disorder]. In conclusion, ketamine should be considered as a valuable treatment option for patients with BD [bipolar disorder] and anhedonia.
Gałuszko-Węgielnik M, Wiglusz MS, Słupski J, Szałach Ł, Włodarczk A, Górska N, Szarmach J, Jakuszkowiak-Wojten K, Wilkowska A, Cubała WJ. Efficacy of Ketamine in bipolar depression: focus on anhedonia. Psychiatr Danub. 2019 Sep;31(Suppl 3):554-560. PMID: 31488790.
When an elevated mood is evident, along with three or more primary symptoms for the majority of the day, on most days of the week, for a minimum of one week, it is classified as a manic episode. Ketamine should not be administered in patients when they are in a state of mania, hypomania, or psychosis.
Manic/Hypomanic Symptoms – A set of behavioral and psychological symptoms associated with manic (more severe) or hypomanic (less severe) episodes.
Elevated or irritable mood – Refers to an abnormally heightened or exaggerated mood state.
Inflated self-esteem/Feeling of grandeur – This refers to an unrealistic or exaggerated sense of self-worth and self-importance.
Decreased need for sleep – A significant reduction in the amount of sleep needed by an individual during a manic or hypomanic episode.
Racing thoughts – This symptom refers to a rapid flow of thoughts that can be difficult to control or slow down.
Increased talkativeness – It refers to a noticeable increase in the amount and speed of speech.
Distractibility – Distractibility refers to an increased susceptibility to being easily diverted or interrupted by external or internal stimuli.
Impulsivity or risk-taking behaviors – This symptom involves engaging in actions without considering the potential consequences or risks involved
Increased energy and activity levels – It refers to a significant surge in physical and mental energy during a manic or hypomanic episode.
A depressive episode has to have five or more primary depression symptoms. They must be experienced for the majority of the day, on most days of the week, for at least two weeks in order to be diagnosed.
Depressed or sad mood – Refers to a persistent and pervasive feeling of sadness, emptiness, or low mood.
Loss of interest or pleasure in activities – Also known as anhedonia, involves a decreased ability to experience pleasure or interest in previously enjoyed activities.
Feelings of worthlessness or guilt – Characterized by persistent feelings of worthlessness, excessive or inappropriate guilt, or self-blame.
Changes in appetite or weight – Depression can lead to extreme changes in appetite, leading to either significant weight loss or weight gain.
Sleep disturbances – Depression often disrupts sleep patterns. Some individuals may experience insomnia, which can involve difficulty falling asleep, staying asleep, or waking up too early. Patients in mania or hypomania have on occasion been sleepless of many days on end.
Fatigue or loss of energy – People with depression commonly experience persistent fatigue or a significant decrease in energy levels.
Difficulty concentrating or making decisions – Depression can impact cognitive functioning, as well as difficulties with concentration, memory, and decision-making.
Thoughts of death or suicide – In severe cases of depression, individuals may have recurrent thoughts of death, dying, or suicide.
Although anxiety and bipolar diseases have certain similarities, their sets of symptoms and diagnostic standards differ. Nonetheless, some symptoms may indicate that a person has co-occurring anxiety.
Anxiety in bipolar disorder can also manifest as irritability and rapid streams of thoughts, which may be especially prominent during mixed episodes, where symptoms of mania and depression co-occur.
Individuals may experience difficulty sleeping, even when they are not in a manic state. They may have difficulty sitting still or relaxing due to heightened energy levels and a sense of inner tension.
Constant worrying, anxiousness, and panic attacks are common. Some avoid social settings or getting out of the house. These symptoms may even persist during manic and depressive episodes.
6 treatments in 2-3 weeks / $3000 for 6 dosing sessions
Includes Telehealth, 6 doctor visits and medication
8 treatments in 4 weeks / $3600 for 8 dosing sessions
Includes Telehealth, 8 doctor visits and medication
$125 per Month / $4 per Daily Dose
Telehealth, Follow-ups, and Medication
* Microdosing costs $150 per month for most patients. For patients who require higher dosages, the cost may increase due to the higher cost of the medication. Microdosing patients are required to have an at-home visit before commencing the medication.
The difficult nature of treating bipolar disorders is well known to the medical and psychiatric community, as well as those whom suffer from it. Patients suffering from bipolar disorders are associated with high rates of morbidity, death, and suicide. Many find bipolar disorders resistant to conventional therapies, which is unfortunate. Nevertheless, Ketamine has shown promise as a treatment option for the depressive episodes that are resistant to other forms of therapy. Due to ketamine’s immediate and effective results, the FDA has recently approved its use (Spravato/esketamine) for treating treatment resistant depression and anxiety. AVYIA’s takes ketamine treatment a step further!
More than half of bipolar disorder patients in clinical tests reacted favorably to a single IV ketamine infusion, and a sizable proportion of them experienced remission with multiple doses over several weeks. Similar outcomes have been observed in our practice, where ketamine infusions have helped to immediately reverse the downward spiral of depressive symptoms. Studies have also shown that it has strong antidepressant and anti-suicidal effects, particularly in patients with chemical and structural changes in their brain as a result of prolonged bipolar depression. Ketamine re-structures brain’s anatomy and and re-wires the neurotransmitters back to their normal states in by a process called neuroplasticity. Ketamine does this by enhancing the release of a protein call BDNF, or brain-derived neurotrophic factor, and regulating the neurotransmitter glutamate. It is theorized that ketamine enhances the ability to control mood by forming new synaptic connections between neurons, a process known as synaptogenesis.
Evidence from preclinical studies has shown that ketamine rapidly induces synaptogenesis and reverses the synaptic changes caused by chronic stress, and that these actions are associated with its antidepressant effect.
Wilkowska, A., Szałach Ł., and Cubała, W. J. (2020). Ketamine in Bipolar Disorder: A Review Neuropsychiatric Disease and Treatment, 16: 2707–2717. doi: 10.2147/NDT.S282208 PMCID: PMC7670087 PMID: 33209026 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670087/
Under the supervision of a trained clinician, ketamine is safe and effective. Ketamine has a safety track record stemming from the 1960s to 1970s, where it was used initially as an anesthetic. Side effects are typically infrequent or well-tolerated, as AVYIA’s program uses lower doses of ketamine compared to anesthetic doses. Ketamine’s dissociative effects are also called out-of-body experiences, psychedelic effects, or trips. These effects are short lasting with our IV and intranasal treatment programs, and completely avoided with our microdosing treatments.
Standard therapy for bipolar disorders consists of mood stabilizers, anti-psychotics, and serotonin re-uptake inhibitors, or SSRIs. In an NIH study, SSRI side effects have been reported in approximately 38% of patients taking SSRIs. Often times these side effects are severe or unpleasant. SSRI side effects include worsening a patient’s mental health symptoms, sexual dysfunction, insomnia, headache, dry mouth, nausea, and weight gain. Mood stabilizers and anti-psychotics also have a reputation for potential serious side effects.
Despite all the potential side effects seen in standard therapy pharmaceuticals, we are not encouraging patients to come off of their existing medications, as doing so without medical supervision can be dangerous. We are encouraging patients to explore ketamine as an additional weapon in their arsenal to combat mental health disorders. Patients should continue working with their mental health providers even after ketamine treatments are completed.
This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response.
Zarate, C.A. Jr, Brutsche, N.E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., Selter, J., Marquardt, C.A., Liberty, V., & Luckenbaugh, D.A. (2012). Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biological Psychiatry, 71(11), 939-946. doi: 10.1016/j.biopsych.2011.12.010. https://pubmed.ncbi.nlm.nih.gov/22297150
Ketamine should not be administered when patients are in an active state of mania, hypomania, or psychosis. Ketamine’s psychoactive properties could intensify these symptoms and lead to negative outcomes. Ketamine therapy is indicated for use in the treatment of bipolar depression when the patients are in remission of their manic or hypomanic states. Before treatment, your provider will take into account the individual’s current medical and psychiatric condition to determine if ketamine is appropriate at that time.
Ketamine is best taken intravenously, where 100% of the drug is absorbed through the blood stream. The IV route delivers the drug in a steady and consistent flow over time, where as nasal inhalation is slightly more abrupt in its onset of drug effect.
The intranasal route has the benefit of avoiding an IV needle poke, however 8 intranasal sessions are required instead of the IV route’s 6 session. Both routes can achieve similar results after completion of the treatment program, so patients can choose which route suits them best.
Microdosing takes a different approach compared to the IV and intranasal program. Microdosing is taken daily, in smaller doses to avoid the dissociative and psychedelic effects of ketamine. Symptoms relief is delayed somewhat compared to the IV and intranasal routes. However, many patients have reported feeling better even on day one!
Results vary from patient to patient and study to study. If we were to combine the most recent body of science papers studying ketamine infusions, approximately 60-80% of patients reported improvement in their moods after multiple treatments. A 2020 review of the science by Wilkowska, et al, reported a 63.2-73.7% remission rate after 6 low-dose ketamine treatments. Single treatment sessions reported less favorable results compared to multiple treatments.
AVYIA recommends combining ketamine infusions with ketamine-assisted psychotherapy (KAP), which consists of individualized guidance with a licensed therapist, so that the positive effects are increased.
AVYIA’s daily microdosing ketamine program is quite comparable to current standard therapies, yet potentially produces results just as effective, or better, while being safer. Standard therapy also requires numerous doctor appointments and prescription drugs, adding more to medical costs.
Ketamine infusions may have a higher initial cost compared to a typical doctor’s visit and medication copay. Yet, when one considers the toll that chronic depression has one’s job and personal life, quickly achieving disease remission is certainly something one should not afford to overlook. Returning back to one’s normal state quickly with ketamine might be a wise financial investment, and investment in one’s future happiness and well-being.
Yes. Ketamine is safe under the supervision of a trained clinician. Since its introduction into clinical trials in 1990, low-dose ketamine infusion therapy has been shown to be both safe and effective in treating depression and a variety of other mental health disorders. Ketamine was FDA approved since the 1970s as an anesthetic, and has been shown to be relatively safe despite the higher anesthetic doses.
Ketamine may induce a psychedelic or dissociative effect. Although typically short lasting, it is important not to drive or do anything potentially dangerous while under the influence. We require a responsible to be present with each IV or intranasal treatment so that the patient can be monitored afterwards.
There are certain medical conditions that are contraindicated with starting ketamine, therefore consulting with AVYIA’s clinicians is an important screening requirement.
IV ketamine is administer 6 times over 3 weeks.
Patients who elect the intranasal route will receive 8 treatments over 4 weeks.
A booster treatment may be required if the patients symptoms relapse or come back. We cannot predict if and when a patient may have symptom relapse, but we always strive for remission of the disease.
Yes, it is legal. It has been FDA approved as an anesthetic since 1970, and it is commonly prescribed off-label for various ailments such as acute or chronic pain, and recently for mental health disorders. 1/5 to 1/4 of all prescription medications are prescribed off-label, meaning it is a standard practice of health care providers.
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