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Ketamine infusions for depression | Depression scoring | Inflammation and brain shrinkage from depression – why you should worry | NOVA Health Recovery Ketamine Infusion Center Fairfax, Virginia 22304

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Depression may be, in part, a chemical imbalance in the brain, such as aberrant serotonin (‘the happy neurotransmitter) or dopamine (the molecule of reward) levels. However, depression can be initiated at several levels, including the gut, due to alterations in the gut microbiome and general inflammation. It has been found that elevated markers of inflammation, such as C-reactive protein (CRP) and Interleukin-6 (IL-6) can be markers of and lead to increased depression. These markers rise in stress, obesity, general medical illness, and from gut dysbiosis (poor microbial health in the gut) to name a few. This can lead to brain fog, poor motivation, difficulty with concentration, memory loss, difficulty making decisions (executive functioning), poor processing speed, and even weight gain.  

Over 7 % of the nation suffers from depression – that is about 16.1 million people, per the National Institutes of Mental Health. Women are twice as likely to be depressed as are men. Some of this may be due to hormonal imbalances. The chance of women becoming depressed in their lifetime is 21-45 % while it is 10-30% for men. 

There are multiple causes for depression, which include stress, poor nutrition, genetics, medications, general medical illness, obesity, lack of exercise, poor sleep, drugs and alcohol, leaky gut, hormonal imbalances, inflammation, and several other factors.  

We frequently assess depression by using the basic PHQ-9 – the physicians health questionnaire that is 9 questions based on a scale of 0-3. The questions are based on the last two weeks of feelings: Link to a PHQ calculator 

1.Little interest or pleasure in doing things 

2.Feeling down, depressed or hopeless 

3.Trouble falling asleep, staying asleep, or sleeping too much 

4.Feeling tired or having little energy 

5.Poor appetite or overeating 

6.Feeling bad about yourself – or that you’re a failure or have let yourself or your family down 

7.Trouble concentrating on things, such as reading the newspaper or watching television 

8.Moving or speaking so slowly that other people could have noticed. Or the opposite – being so fidgety or restless that you have been moving around a lot more than usual 

9.Thoughts that you would be better off dead or of hurting yourself in some way 

These are scored on a scale of 0-3: 

0 – for not at all 

1- For several days in the past two weeks 

2- For more than half the days 

3–  For nearly every day. 

The score results are graded as the following: 

Score Depression Severity Treatment 
0 – 4 None-minimal None 
5 – 9 Mild Watchful waiting; repeat PHQ-9 at follow-up 
10 – 14 Moderate Treatment plan, considering counseling, follow-up and/or pharmacotherapy 
15 – 19 Moderately Severe Active treatment with pharmacotherapy and/or psychotherapy 
20 – 27 Severe Immediate initiation of pharmacotherapy and, if severe impairment or poor response to therapy, expedited referral to a mental health specialist for psychotherapy and/or collaborative management 

The importance of treating depression is several fold. One is to get you feeling better. Many patients will eat excessively and gain weight to comfort themselves. Excess adipose tissue results in inflammation in the brain that leads to further depression and cognitive deficits. Others may resort to self-medication with alcohol or opioids that leads to addiction. In other cases, the person may continue a downward spiral in both their personal life, with family discord and personal unfulfillment, as well as work-related loss, such as absenteeism and presenteeism (showing up but not doing their job). The ability to concentrate and focus is much worse when depression sets in. In fact, depression has been found to physically decrease the size of the hippocampus on MRI(the memory center of the brain) as well as the prefrontal cortex (involved with decision-making and executive functioning).  See the following general mainstream article: Chronic Depression Shrinks the Brain’s Memories and Emotions  (ENIGMA research) .  

An individual who is depressed and sitting in a room will continue to have their hippocampus and prefrontal cortex shrink due to depression and the inflammation that results. Such individuals will have difficult with memory, emotional regulation, processing speed, and decision-making. Aggressive treatment for depression should be sought as it is possible to regenerate these vital areas of the brain with treatment, such as Ketamine therapy and lifestyle interventions like exercise and nutrition. Concerning nutritionhigh adherence to dietary recommendations, anti-inflammatory diet, fish consumption, exclusion of processed foods, and adequate intake of folic acid, magnesium different fatty acids, were associated with a reduced risk of mental illness. Suggestions for nutritional changes can be found at nutritionfactshealthyplacenutritionkits, and everydayhealth as a few options for ideas. 

Ketamine therapy, as a series of infusions, demonstrates rapid reversal of depression and suicidality. It is an anti-inflammatory agent that increases Brain Derived Neurotrophic Factor (BDNF) to increase neuroplasticity and allows the formation of new connections in the brain. This decreases depression and can be seen on MRI’s to increase the volume and functioning of the hippocampus (memory center). We will discuss more information regarding ketamine therapies in upcoming articles. Refer to NOVA Health Recovery for more information as well. 

Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment  

J Psychiatry Neurosci. 2010 Sep; 35(5): 337–343.doi: 10.1503/jpn.100002 

Redlich, R., Opel, N., Bürger, C. et al. The Limbic System in Youth Depression: Brain Structural and Functional Alterations in Adolescent In-patients with Severe Depression. Neuropsychopharmacol. 43, 546–554 (2018). https://doi.org/10.1038/npp.2017.246 

Hippocampal Volume and Depression: A Meta-Analysis of MRI Studies  

Jacka, F.N., Cherbuin, N., Anstey, K.J. et al. Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC Med 13, 215 (2015). https://doi.org/10.1186/s12916-015-0461-x 

Gujral S, Aizenstein H, Reynolds CF 3rd, Butters MA, Erickson KI. Exercise effects on depression: Possible neural mechanisms. Gen Hosp Psychiatry. 2017 Nov;49:2-10. doi: 10.1016/j.genhosppsych.2017.04.012. PMID: 29122145; PMCID: PMC6437683

Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and Depression Ljungberg T, Bondza E, Lethin C. Evidence of the Importance of Dietary Habits Regarding Depressive Symptoms and Depression. Int J Environ Res Public Health. 2020;17(5):1616. Published 2020 Mar 2. doi:10.3390/ijerph17051616 

Huang Q, Liu H, Suzuki K, Ma S, Liu C. Linking What We Eat to Our Mood: A Review of Diet, Dietary Antioxidants, and Depression. Antioxidants (Basel). 2019;8(9):376. Published 2019 Sep 5. doi:10.3390/antiox8090376 

Koebnick C, Black MH, Wu J, et al. A diet high in sugar-sweetened beverage and low in fruits and vegetables is associated with adiposity and a pro-inflammatory adipokine profile. Br J Nutr. 2018;120(11):1230-1239. doi:10.1017/S0007114518002726 

Vermeulen E, Stronks K, Snijder MB, Schene AH, Lok A, de Vries JH, Visser M, Brouwer IA, Nicolaou M. A combined high-sugar and high-saturated-fat dietary pattern is associated with more depressive symptoms in a multi-ethnic population: the HELIUS (Healthy Life in an Urban Setting) study. Public Health Nutr. 2017 Sep;20(13):2374-2382. doi: 10.1017/S1368980017001550. Epub 2017 Jul 20. PMID: 28724468. 

Opie RS, Itsiopoulos C, Parletta N, Sanchez-Villegas A, Akbaraly TN, Ruusunen A, Jacka FN. Dietary recommendations for the prevention of depression. Nutr Neurosci. 2017 Apr;20(3):161-171. doi: 10.1179/1476830515Y.0000000043. Epub 2016 Mar 2. PMID: 26317148. 

Depression Nutrition Fact Sheet  

Healthy Eating and depression 

Eating your way to recovery in depression 

Food For the Brain 

Ketamine and its effects on the brain and mental health 

Zhou, Y., Wu, F., Liu, W. et al. Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis. Transl Psychiatry 10, 264 (2020). https://doi.org/10.1038/s41398-020-00945-9  

Ionescu DF, Felicione JM, Gosai A, et al. Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature. Harv Rev Psychiatry. 2018;26(6):320-339. doi:10.1097/HRP.0000000000000179 

https://www.researchgate.net/publication/264794534_Hippocampal_Volume_And_The_Rapid_Antidepressant_Effect_Of_Ketamine

Prefrontal Cortex Connectivity and BDNF Fluctuations May Play a Role in Ketamine Mechanism of Action 

Corriger A, Pickering G. Ketamine and depression: a narrative review. Drug Des Devel Ther. 2019;13:3051-3067. Published 2019 Aug 27. doi:10.2147/DDDT.S221437 

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703-844-0184 | NORTHERN VIRGINIA KETAMINE CENTER FOR DEPRESSION | NOVA HEALTH RECOVERY | Esketamine Virginia | Intranasal Ketamine for depression : BMJ | SPRAVATO CENTER OF FAIRFAX | INTRANSAL KETAMINE CENTER | 22304 22306 | Fairfax, Va | Reston Virginia Ketamine Infusion Center | Ketamine Doctor near me | Loudoun County Ketamine| 22201 | Arlington Ketamine Center

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link



Ketamine could be first of new generation of rapid acting antidepressants, say experts

Ketamine is the first truly new pharmacological approach to treating depression in the past 50 years and could herald a new generation of rapid acting antidepressants, researchers have predicted.

“We haven’t had anything really new for about 50 or 60 years,” said Allan Young, professor of mood disorders at the Institute of Psychiatry, Psychology and Neuroscience at King’s College, London, at a briefing on 12 July at London’s Science Media Centre.

Most of the new launches have been “tinkering with drugs which were really discovered in the ’50s and ’60s,” he explained. “Even the famous Prozac, which came in in the late ’80s, is really just a refinement of the tricyclic antidepressants that came in the ’50s. People say we are still in the age of steam, and we need to go to the next technological advance.”

Slow onset

In the past few years the focus has fallen on ketamine, which is used for pain relief and anaesthesia but is better known for being a horse sedative and a “club drug” that can induce hallucinations and calmness. It has been found to have rapid antidepressant effects and to be effective in many patients with treatment resistant depression.

US clinics increasingly offer IV infusions of ketamine off label, and in March esketamine, a nasal ketamine based drug, was approved by the US Food and Drug Administration for treatment resistant depression,1 at a cost of £32 400 (€36 060; $40 615) per patient per year.

Carlos Zarate, chief of the Experimental Therapeutics and Pathophysiology Branch at the US National Institute of Mental Health, who has been a key figure in the discovery and evaluation of ketamine as an antidepressant, said that one of the main problems with current antidepressants was their speed of onset in terms of antidepressant and anti-suicidal effects.

He explained that it took 10-14 weeks to see significant improvement with monoaminergic based antidepressants. “In my mind that is too slow,” he said. “We are focusing on treatments that can produce results within hours. That is where we are heading with the next generation of antidepressant, and ketamine is now the prototype for future generation antidepressants which will have rapid, robust antidepressant effects—rapid within a few hours.”

Efficacy and tolerability

Zarate said that, besides correcting chemical imbalances of serotonin and norepinephrine, the new generation of ketamine based antidepressants had other effects such as enhancing plasticity and restoring the synapses and dendrite circuits that shrivel in depression.

When ketamine is given to patients it binds to the N-methyl-D-aspartate (NMDA) receptor, causing a series of transient side effects including decreased awareness of the environment, vivid dreams, and problems in communicating. But the half life of ketamine is only two to three hours, so these side effects quickly subside, whereas the therapeutic effects of the drug last seven days or longer.

Zarate’s team is now focusing on the 24 metabolites of ketamine to hone the drug’s efficacy and tolerability. One of these, hydroxynorketamine, has already been shown to have similar antidepressive effects to ketamine in animals, without the side effects, and it is due to be tested in patients this autumn.

“Ketamine may actually be a prodrug for hydroxynorketamine,” said Zarate.

High cost

A few dozen patients with treatment resistant depression have been treated with ketamine in UK trials, and the European Medicines Agency and the Medicines and Healthcare Products Regulatory Agency are due to reach a decision on authorising esketamine for marketing in October. If the drug is approved private clinics will be able to provide it. But it would be unlikely to be available through the NHS until at least 2020, if at all, as the National Institute for Health and Care Excellence would need to deem it cost effective.

Rupert McShane, consultant psychiatrist and associate professor at the University of Oxford, said that, as well as the likely high cost of esketamine, patients treated with it must be observed in a clinic for two hours after each administration. This would require substantial clinical time, as esketamine is given twice a week for the first month, once a week for the second month, and once a week or once a fortnight from then on.

McShane also recommended that, if approved, a multidrug registry should be set up to monitor the long term safety and effectiveness of ketamine based drugs. Patients would be asked to input their use of any prescribed ketamine, esketamine, or any other future ketamine based product, as well as any self medication with illicit ketamine.

References


    1. Silberner J
    . Ketamine should be available for treatment resistant depression, says FDA panel. BMJ2019;364:l858.doi:10.1136/bmj.l858 pmid:30796014FREE Full TextGoogle Scholar